- A new organometallic palladium(II) compound derived of 2,6-diacetylpyridine mono(thiosemicarbazone): Synthesis, spectroscopic properties and crystal structure of two solvatomorphic forms
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Preparation and characterization of a novel 2,6-diacetylpyridine mono(4-methoxyphenyl-thiosemicarbazone), H2L, is described. Treatment of H2L with PdCl2(PPh3)2 gave the neutral mononuclear complex [Pd
- Matesanz, Ana I.,Hernández, Carolina,Souza, Pilar
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- New thiosemicarbazide-1,2,3-triazole hybrids as potent α-glucosidase inhibitors: Design, synthesis, and biological evaluation
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A new series of thiosemicarbazide-1,2,3-triazole hybrids 10a-o has been synthesized, characterized by 1H NMR, 13C NMR, and screened for their in vitro α-glucosidase inhibitory activity. All of the synthesized compounds displayed excellent α-glucosidase inhibitory activity with IC50 values in the range of 75.0 ± 0.5 to 253.0 ± 0.5 μM, as compared to the standard drug acarbose (IC50 = 750.0 ± 1.5 μM). Among the synthesized compounds, compound 10h (IC50 = 75.0 ± 0.5)with 4-methoxy group at phenyl part of thiosemicarbazide moiety and 2,6-dichloro substituents at benzyl moiety was found to be the most potent compound. Kinetic analysis revealed that compound 10h is a competitive inhibitor for α-glucosidase. Docking study of compound 10h in the active site of α-glucosidase showed that this compound interacted with residues His239, His279, Glu304, Gly306, and Arg312.
- Bakherad, Zohreh,Mohammadi-Khanaposhtani, Maryam,Sadeghi-Aliabadi, Hojjat,Rezaei, Sepideh,Fassihi, Afshin,Bakherad, Mohammad,Rastegar, Hossein,Biglar, Mahmood,Saghaie, Lotfollah,Larijani, Bagher,Mahdavi, Mohammad
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- Oxadiazol-based mTOR inhibitors with potent antiproliferative activities: synthetic and computational modeling
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Series of N-aryl-1,3,4-oxadiazole-2-amines and 3-aryl-1,2,4-oxadiazole-5-carboxamides derivatives were synthesized as novel chemotherapeutic agents. Synthesized compounds were evaluated for their anticancer activities against several cancer cell lines. Many analogues of 1,3,4-oxadiazole scaffold showed potent antiproliferative activities against breast cancer cell lines, with higher activities toward the metastatic breast cancer cell line (MDA-MB-231). Active analogues were profiled using in-house pharmacophore database in search for molecular target. Active analogues (2j and 2k) were found to fit the pharmacophoric map of ATP-competitive inhibitors of mTOR. The mTOR inhibitory activities of the most active compounds were confirmed with IC50 values in nanomolar range. The N-aryl-1,3,4-oxadiazole-2-amines linked to a basic head is a novel ATP-competitive inhibitors of mTOR with potential activities for treatment of different types of cancer. Graphical abstract: [Figure not available: see fulltext.].
- Khanfar, Mohammad A.
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- Diaryl-substituted thiosemicarbazone: A potent scaffold for the development of New Delhi metallo-β-lactamase-1 inhibitors
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The superbug infection caused by New Delhi metallo-β-lactamase (NDM-1) has become an emerging public health threat. Inhibition of NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. A potent scaffold, diaryl-substituted thiosemicarbazone, was constructed and assayed with metallo-β-lactamases (MβLs). The obtained twenty-six molecules specifically inhibited NDM-1 with IC50 0.038–34.7 μM range (except 1e, 2e, and 3d), and 1c is the most potent inhibitor (IC50 = 0.038 μM). The structure-activity relationship of synthetic thiosemicarbazones revealed that the diaryl-substitutes, specifically 2-pyridine and 2-hydroxylbenzene improved inhibitory activities of the inhibitors. The thiosemicarbazones exhibited synergistic antimycobacterial actions against E. coli-NDM-1, resulted a 2–512-fold reduction in MIC of meropenem, while 1c restored 16–256-, 16-, and 2-fold activity of the antibiotic on clinical isolates ECs, K. pneumonia and P. aeruginosa harboring NDM-1, respectively. Also, mice experiments showed that 1c had a synergistic antibacterial ability with meropenem, reduced the bacterial load clinical isolate EC08 in the spleen and liver. This work provided a highly promising scaffold for the development of NDM-1 inhibitors.
- Li, Jia-Qi,Sun, Le-Yun,Jiang, Zhihui,Chen, Cheng,Gao, Han,Chigan, Jia-Zhu,Ding, Huan-Huan,Yang, Ke-Wu
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- Synthesis and antimicrobial activities of new thiosemicarbazones and thiazolidinones in indole series
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Abstract: New thiosemicarbazones were synthesized in excellent yield reaction of indole derivatives with thiosemicarbazides. These thiosemicarbazones were reacted with ethyl bromoacetate to produce original heterocyclic-substituted indole derivatives possessing a 4-oxo-thiazolidine group. Analytical IR and NMR spectra and elemental analysis were performed to reveal their structures. The antimicrobial activity of all synthesized compounds was evaluated for antibacterial activity in vitro against Gram-positive and Gram-negative bacteria. Antibacterial screening data showed that two compounds demonstrated activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. These preliminary results indicate that some of these newly synthesized compounds show a promising antibacterial potency. Graphic abstract: [Figure not available: see fulltext.].
- Benmohammed, Abdelmadjid,Djafri, Ayada,Kadiri, Mokhtaria,Khoumeri, Omar,Louail, Ahmed Amine,Rekiba, Nawel,Sehanine, Yassine,Terme, Thierry,Vanelle, Patrice
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p. 977 - 986
(2021/08/13)
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- Synthesis and Antiproliferative Activity of New Thiosemicarboxamide Derivatives
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To discover new anticancer agents, two series of thiosemicarboxamide derivatives were synthesized and evaluated for their antiproliferative activity against human cancer cells in vitro. Most target compounds (especially 3f, 3g, and 3h) exhibit potent antiproliferative activity against HeLa cells. Importantly, compound 3h, bearing a 4-methylphenyl substituent at N position of thiourea moiety, has significant and broad-spectrum inhibitory activities against cancer cells (HepG2, HeLa, MDA-MB231, A875, and H460 cells) with low IC50 values (5.0 μM) and shows low toxicity to normal LO2 and MRC-5 cells. Further studies show that compound 3h exerts high inhibitory activity in cancer cells by inducing the G2/M-phase arrest of cancer cells. Collectively, this study presents compound 3h as a new entity for the development of cell cycle arrest inducers for the treatment of cancer.
- Chen, Jun,Fang, Meijuan,Guo, Yafei,Hu, Hongyu,Hu, Sangsang,Sun, Ke,Wu, Jun,Xue, Yuhua
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- Preparation and application of thiosemicarbazone compound
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The invention discloses a thiosemicarbazone compound, and biological activity analysis is carried out on the thiosemicarbazone compound. The invention also discloses application of the thiosemicarbazone compound in preparation of antibacterial drugs. According to the invention, important intermediates 6a-6h are synthesized from hydrazine hydrate and react with adamantane benzaldehyde respectivelyto synthesize eight adamantane aromatic aldehyde thiosemicarbazone compounds, the structures of the compounds can be confirmed by infrared, nuclear magnetic hydrogen spectrum, carbon spectrum and massspectrum methods, and the antibacterial activity of the compounds is tested in vitro. The result shows that the compound has a good antibacterial effect on escherichia coli and bacillus subtilis.
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Paragraph 0010; 0014; 0015
(2021/02/20)
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- Carbazole-based semicarbazones and hydrazones as multifunctional anti-Alzheimer agents
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With the aim to combat a multi-faceted neurodegenerative Alzheimer’s disease (AD), a series of carbazole-based semicarbazide and hydrazide derivatives were designed, synthesized and assessed for their cholinesterase (ChE) inhibitory, antioxidant and biometal chelating activity. Among them, (E)-2-((9-ethyl-9H-carbazol-3-yl)methylene)-N-(pyridin-2-yl)hydrazinecarbothioamide (62) and (E)-2-((9-ethyl-9H-carbazol-3-yl)methylene)-N-(5-chloropyridin-2-yl)hydrazinecarbothioamide (63) emerged as the premier candidates with good ChE inhibitory activities (IC50 values of 1.37 μM and 1.18 μM for hAChE, IC50 values of 2.69 μM and 3.31 μM for EqBuChE, respectively). All the test compounds displayed excellent antioxidant activity (reduction percentage of DPPH values for compounds (62) and (63) were 85.67% and 84.49%, respectively at 100 μM concentration). Compounds (62) and (63) conferred specific copper ion chelating property in metal chelation study. Molecular docking studies of compounds (62) and (63) indicate strong interactions within the active sites of both the ChE enzymes. Besides that, these compounds also exhibited significant in silico drug-like pharmacokinetic properties. Thus, taken together, they can serve as a starting point in the designing of multifunctional ligands in pursuit of potential anti-AD agents that might further prevent the progression of ADs. Communicated by Ramaswamy H. Sarma.
- Chaudhary, Bharat N.,Gandhi, Bhumi,Kanhed, Ashish M.,Patel, Dushyant V.,Patel, Kirti V.,Patel, Kishan B.,Patel, Nirav R.,Prajapati, Navnit K.,Shah, Bhavik S.,Teli, Divya M.,Yadav, Mange Ram
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- Synthesis and antibacterial activity of novel Schiff bases of thiosemicarbazone derivatives with adamantane moiety
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Increased bacterial resistance to antibiotics is a major threat to human health, and it is particularly important to develop novel antibiotic drugs. Here, we designed a series of Schiff base thiosemicarbazone derivatives containing an adamantane moiety, and carried out the structural characterization of the compounds and in vitro antibacterial activity tests. Compound 7e was as effective as the commonly used antibiotic ampicillin against the Gram-negative bacterium Escherichia coli, and compound 7g had a good inhibitory effect against Gram-positive Bacillus subtilis. These findings provide data for the development of better thiosemicarbazone antibacterial agents.
- Zhu, Jiahui,Teng, Guosheng,Li, Dongfeng,Hou, Ruibin,Xia, Yan
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p. 1534 - 1540
(2021/06/16)
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- Thiosemicarbazone-based lead optimization to discover high-efficiency and low-toxicity anti-gastric cancer agents
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In this paper, a series of thiosemicarbazone derivatives containing different aromatic heterocyclic groups were synthesized and the tridentate donor system of the lead compound was optimized. Most of the target compounds showed improved antiproliferative activity against MGC803 cells. SAR studies revealed that compound 5d displayed significant advantages in inhibition effect with an IC50 value of 0.031 μM, and better selectivity between cancer and normal cells than 3-AP and DpC (about 15- and 5-fold improved respectively). Besides, compound 5d showed selective antiproliferative activity in not only other cancer cells but also different gastric cancer cell lines. In-depth mechanism studies showed that compound 5d could induce mitochondria-related apoptosis which might be related to the elevation of intracellular ROS level, and cause cell cycle arrest at S phase. Moreover, 5d could evidently suppress the cell migration and invasion by blocking the EMT (epithelial–mesenchymal transition) process. Consequently, our studies provided a lead optimization strategy of thiosemicarbazone derivatives which would contribute to discover high-efficiency and low-toxicity agents for the treatment of gastric cancer.
- Bo-Wang,He, Zhang-Xu,Li, Yi-Han,Liu, Hong-Min,Ma, Li-Ying,Ma, Qin,Tao, Yuan-Yuan,Wang, Hao-Jie,Wu, Hui-Pan,Zhang, Xin-Hui,Zhao, Bing
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- 1,3,4-thiadiazine compound and application thereof
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The invention relates to a 1,3,4-thiadiazine compound, and the chemical structure of the compound is shown as a formula (I). The provided compound has a remarkable inhibition effect on human cervicalcancer cells Hela and human colon cancer cells HCT116, a
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Paragraph 0023; 0026-0027
(2020/08/06)
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- Novel indol-3-yl-thiosemicarbazone derivatives: Obtaining, evaluation of in vitro leishmanicidal activity and ultrastructural studies
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Parasitic diseases still represent serious public health problems, since the high and steady emergence of resistant strains is evident. Because parasitic infections are distributed predominantly in developing countries, less toxic, more efficient, safer and more accessible drugs have become desirable in the treatment of the infected population. This is the case of leishmaniasis, an infectious disease caused by a protozoan of the genus Leishmania sp., responsible for triggering pathological processes from the simplest to the most severe forms leading to high rates of morbidity and mortality throughout the world. In the search for new leishmanicidal drugs, the thiosemicarbazones and the indole fragments have been identified as promising structures for leishmanicidal activity. The present study proposes the synthesis and structural characterization of new indole-thiosemicarbazone derivatives (2a-j), in addition to performing in vitro evaluations through cytotoxicity assays using macrophages (J774) activity against forms of Leishmania infantum and Leishmania amazonensis promastigote as well as ultrastructural analyzes in promastigotes of L. infantum. Results show that the indole-thiosemicarbazone derivatives were obtained with yield values varying from 32.09 to 94.64%. In the evaluation of cytotoxicity, the indole-thiosemicarbazone compounds presented CC50 values between 53.23 and 357.97 μM. Concerning the evaluation against L. amazonensis promastigote forms, IC50 values ranged between 12.31 and > 481.52 μM, while the activity against L. infantum promastigotes obtained IC50 values between 4.36 and 23.35 μM. The compounds 2d and 2i tested against L. infantum were the most promising in the series, as they showed the lowest IC50 values: 5.60 and 4.36 respectively. The parasites treated with the compounds 2d and 2i showed several structural alterations, such as shrinkage of the cell body, shortening and loss of the flagellum, intense mitochondrial swelling and vacuolization of the cytoplasm leading the parasite to cellular unviability. Therefore, the indole-thiosemicarbazone compounds are promising because they yield considerable synthesis, have low cytotoxicity to mammalian cells and act as leishmanicidal agents.
- da Silva, Paula Roberta,de Oliveira, Jamerson Ferreira,da Silva, Anekécia Lauro,Queiroz, Camila Marques,Feitosa, Ana Paula Sampaio,Duarte, Denise Maria Figueiredo Araújo,da Silva, Aline Caroline,de Castro, Maria Carolina Accioly Brelaz,Pereira, Valéria Rêgo Alves,da Silva, Rosali Maria Ferreira,Alves, Luiz Carlos,dos Santos, Fábio André Brayner,de Lima, Maria do Carmo Alves
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- Synthesis, characterization, and antioxidant activity of some new N 4-arylsubstituted-5-methoxyisatin-β-thiosemicarbazone derivatives
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Abstract: Firstly, thiosemicarbazides were prepared by the reaction of hydrazine monohydrate with isothiocyanates in cold dry ethanol at 0?°C for 1?h. After that, new isatin-β-thiosemicarbazones were synthesized by treatment of 5-methoxyisatin with thiose
- Mu?lu, Halit
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p. 2083 - 2098
(2020/01/13)
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- Synthesis of novel quinoline-thiosemicarbazide hybrids and evaluation of their biological activities, molecular docking, molecular dynamics, pharmacophore model studies, and ADME-Tox properties
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In the present study, a novel series of N-((substituted)carbamothioyl)-2,4-dimethylquinoline-3-carboxamide (7a-7s) was synthesized by microwave-assisted method. Structure of these derivatives was examined by spectroscopic techniques such as 1H NMR, 13C NMR, FT-IR, and ESI-MS. Further, the novel synthesized compounds were evaluated for their in-vitro biological activities against antibacterial, antifungal, antimalarial, and antituberculosis activity as well as for in-silico study. The antimalarial results demonstrated that compounds 7c and 7q (0.02 μg/mL) have notable potency against Plasmodium falciparum compared with chloroquine (0.02 μg/mL); compounds 7l (0.10 μg/mL), 7e, 7s (0.19 μg/mL), 7b, 7p (0.15 μg/mL), 7a, 7f, and 7f (0.25 μg/mL) also exhibited good activity against P. falciparum compared with quinine (0.26 μg/mL) as standard drug. Docking was performed on PFDHFR-TS, given the effect of compounds against the P. falciparum strain was excellent in comparison with standard drug. Molecular docking suggested that compounds 7b, 7i and 7c, 7e, and 7l closely bind with the active site of protein 3JSU and 4DP3, respectively, and compared with biological activity. We have also carried out molecular dynamics simulation on the best dock compound 7e complex with PDB: 3JSU to check the stability of docked complex and their molecular interaction. The calculated ADME-Tox descriptors for the synthesized compounds validated good pharmacokinetics properties, suggesting that these compounds could be used as hit for the development of the new active agents.
- Darji, Drashti G.,Patel, Dhaval B.,Patel, Hitesh D.,Patel, Krupa R.,Rajani, Dhanji P.,Rajani, Smita D.
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- Synthesis, molecular modeling and antiviral activity of novel 5-fluoro-1H-indole-2,3-dione 3-thiosemicarbazones
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In this work, novel 5-fluoro-1-methyl/ethyl-1H-indole-2,3-dione 3-[4-(substituted phenyl)-thiosemicarbazones] 6a-n and 7a-n were synthesized. The antiviral effects of the compounds were tested against HSV-1 (KOS), HSV-2 (G) HSV-1 TK- KOS ACVr and VV in HEL cell cultures using acyclovir and ganciclovir as standards, and Coxsackie B4 virus in Vero cell cultures using ribavirin and mycophenolic acid as standards. R2 ethyl substituted 7 derivatives were found effective against viruses tested. R1 4-CF3 substituted 7d, R1 4-OCH3 substituted 7 g and R1 3-Cl substituted 7 l showed activity against HSV-1 (KOS), HSV-2 (G) HSV-1 TK- KOS ACVr and VV. Whereas only R1 4-Br substituted 7n has selective activity against coxsackie B4 virus. Molecular modeling studies of 7d and 7l were performed to determine binding side on HSV-1 glycoprotein B and D, HSV-2 glycoprotein B structures.
- ?zbil, Mehmet,Duran, Gizem Nur,Karal?, Nilgün,Sevin?li, Zekiye ?eyma
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- Functionalized Oxoindolin Hydrazine Carbothioamide Derivatives as Highly Potent Inhibitors of Nucleoside Triphosphate Diphosphohydrolases
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Ectonucleoside triphosphate diphosphohydrolases (NTPDases) are ectoenzymes that play an important role in the hydrolysis of nucleoside triphosphate and diphosphate to nucleoside monophosphate. NTPDase1, -2, -3 and -8 are the membrane bound members of this enzyme family that are responsible for regulating the levels of nucleotides in extracellular environment. However, the pathophysiological functions of these enzymes are not fully understood due to lack of potent and selective NTPDase inhibitors. Herein, a series of oxoindolin hydrazine carbothioamide derivatives is synthesized and screened for NTPDase inhibitory activity. Four compounds were identified as selective inhibitors of h-NTPDase1 having IC50 values in lower micromolar range, these include compounds 8b (IC50 = 0.29 ± 0.02 μM), 8e (IC50 = 0.15 ± 0.009 μM), 8f (IC50 = 0.24 ± 0.01 μM) and 8l (IC50 = 0.30 ± 0.03 μM). Similarly, compound 8k (IC50 = 0.16 ± 0.01 μM) was found to be a selective h-NTPDase2 inhibitor. In case of h-NTPDase3, most potent inhibitors were compounds 8c (IC50 = 0.19 ± 0.02 μM) and 8m (IC50 = 0.38 ± 0.03 μM). Since NTPDase3 has been reported to be associated with the regulation of insulin secretion, we evaluated our synthesized NTPDase3 inhibitors for their ability to stimulate insulin secretion in isolated mice islets. Promising results were obtained showing that compound 8m potently stimulated insulin secretion without affecting the NTPDase3 gene expression. Molecular docking studies of the most potent compounds were also carried out to rationalize binding site interactions. Hence, these compounds are useful tools to study the role of NTPDase3 in insulin secretion.
- Afzal, Saira,Hameed, Abdul,Iqbal, Jamshed,Pelletier, Julie,Sévigny, Jean,al-Rashida, Mariya
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- Synthesis, cytotoxicity, and in vivo antitumor activity study of parthenolide semicarbazones and thiosemicarbazones
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Parthenolide is an important sesquiterpene lactone with potent anticancer activities. In order to further improve its biological activity, a series of parthenolide semicarbazone or thiosemicarbazone derivatives was synthesized and evaluated for their anti
- Du, Guohua,Jia, Xinxin,Li, Yan,Liu, Qi,Wang, Shiyi,Zeng, Binglin,Zhang, Chen
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- Design and Synthesis of Novel Cytotoxic Indole-Thiosemicarbazone Derivatives: Biological Evaluation and Docking Study
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In this work, two novel series of indole-thiosemicarbazone derivatives were designed, synthesized, and evaluated for their cytotoxic activity against MCF-7, A-549, and Hep-G2 cell lines in comparison to etoposide and colchicine as the reference drugs. Generally, the synthesized compounds showed better cytotoxicity towards A-549 and Hep-G2 than MCF-7. Among them, (2E)-2-{[2-(4-chlorophenyl)-1H-indol-3-yl]methylidene}-N-(4-methoxyphenyl)hydrazinecarbothioamide (8l) was found to be the most potent compound against A-549 and Hep-G2, at least three times more potent than etoposide. The morphological analysis by the acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that compound 8l induced apoptosis in A-549 cells. Moreover, molecular docking methodology was exploited to elucidate the details of molecular interactions of the studied compounds with putative targets.
- Bakherad, Zohreh,Safavi, Maliheh,Fassihi, Afshin,Sadeghi-Aliabadi, Hojjat,Bakherad, Mohammad,Rastegar, Hossein,Saeedi, Mina,Ghasemi, Jahan B,Saghaie, Lotfollah,Mahdavi, Mohammad
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- Novel 4-quinoline-thiosemicarbazone derivatives: Synthesis, antiproliferative activity, in vitro and in silico biomacromolecule interaction studies and topoisomerase inhibition
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Twelve 2-(quinolin-4-ylmethylene) hydrazinecarbothioamide derivatives were synthetized and their biological properties were investigated, among which, the ability to interact with DNA and BSA through UV–Vis absorption, fluorescence, Circular Dichroism, molecular docking and relative viscosity, antiproliferative activity against MCF-7 and T-47D mammary tumor cells and RAW-264.7 macrophages and inhibitory capacity of the enzyme topoisomerase IIα. In the binding study with DNA and BSA, all the compounds displayed affinity for interaction with both biomolecules, especially JF-92 (p-ethyl-substituted), with binding constant of 1.62 × 106 and 1.43 × 105, respectively, and DNA binding mode by intercalation. The IC50 values were obtained between 0.81 and 1.48 μM and topoisomerase inhibition results in 10 μM. Thus, we conclude that the reduction of the acridine to quinoline ring did not disrupt the antitumor action and that substitution patterns are important for biomolecule interaction affinity as they demonstrate the potential of these compounds for anticancer therapy.
- Ribeiro, Amélia Galdino,Almeida, Sinara M?nica Vitalino de,de Oliveira, Jamerson Ferreira,Souza, Tulio Ricardo Couto de Lima,Santos, Keriolaine Lima dos,Albuquerque, Amanda Pinheiro de Barros,Nogueira, Mariane Cajuba de Britto Lira,Carvalho Junior, Luiz Bezerra de,Moura, Ricardo Olímpio de,da Silva, Aline Caroline,Pereira, Valéria Rêgo Alves,Castro, Maria Carolina Accioly Brelaz de,Lima, Maria do Carmo Alves de
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- Thiazolyl-thiadiazines as Beta Site Amyloid Precursor Protein Cleaving Enzyme-1 (BACE-1) Inhibitors and Anti-inflammatory Agents: Multitarget-Directed Ligands for the Efficient Management of Alzheimer's Disease
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Alzheimer's disease (AD) is associated with multiple neuropathological events including β-site amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibition and neuronal inflammation, ensuing degeneracy, and death to neuronal cells. Targeting such a complex disease via a single target directed treatment was found to be inefficacious. Hence, with an intention to incorporate multiple therapeutic effects within a single molecule, multitarget-directed ligands (MTDLs) have been evolved. Herein, for the first time, we report the discovery of novel thiazolyl-thiadiazines that can serve as MTDLs as evident from the in vitro and in vivo studies. These MTDLs exhibited BACE-1 inhibition down to micromolar range, and results from the in vivo studies demonstrated efficient anti-inflammatory activity with inherent gastrointestinal safety. Moreover, compound 6d unveiled noteworthy antioxidant, antiamyloid, neuroprotective, and antiamnesic properties. Overall, results of the present study manifest the potential outcome of thiazolyl-thiadiazines for AD treatment.
- Sagar, Sneha R.,Singh, Devendra Pratap,Panchal, Nirupa B.,Das, Rajesh D.,Pandya, Dhaivat H.,Sudarsanam, Vasudevan,Nivsarkar, Manish,Vasu, Kamala K.
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p. 1663 - 1679
(2018/05/14)
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- Design, synthesis, and biological evaluation of novel oxadiazole- and thiazole-based histamine H3R ligands
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Histamine H3 receptor (H3R) is largely expressed in the CNS and modulation of the H3R function can affect histamine synthesis and liberation, and modulate the release of many other neurotransmitters. Targeting H3R with antagonists/inverse agonists may have therapeutic applications in neurodegenerative disorders, gastrointestinal and inflammatory diseases. This prompted us to design and synthesize azole-based H3R ligands, i.e. having oxadiazole- or thiazole-based core structures. While ligands of oxadiazole scaffold were almost inactive, thiazole-based ligands were very potent and several exhibited binding affinities in a nanomolar concentration range. Ligands combining 4-cyanophenyl moiety as arbitrary region, para-xylene or piperidine carbamoyl linkers, and/or pyrrolidine or piperidine basic heads were found to be the most active within this series of thiazole-based H3R ligands. The most active ligands were in silico screened for ADMET properties and drug-likeness. They fulfilled Lipinski's and Veber's rules and exhibited potential activities for oral administration, blood–brain barrier penetration, low hepatotoxicity, combined with an overall good toxicity profile.
- Khanfar, Mohammad A.,Reiner, David,Hagenow, Stefanie,Stark, Holger
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supporting information
p. 4034 - 4046
(2018/06/30)
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- Synthetic thiosemicarbazones as a new class of Mycobacterium tuberculosis protein tyrosine phosphatase A inhibitors
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Mycobacterium tuberculosis secretes two protein tyrosine phosphatases as virulence factors, PtpA and PtpB. Inhibition studies of these enzymes have shown significant attenuation of the M. tuberculosis growth in vivo. As PtpA mediates many effects on the r
- Sens, Larissa,de Souza, Ana Caroline Arruda,Pacheco, Lucas Antonio,Menegatti, Angela Camila Orbem,Mori, Mattia,Mascarello, Alessandra,Nunes, Ricardo José,Terenzi, Hernán
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p. 5742 - 5750
(2018/11/03)
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- Aromatic amine substituted - 1, 2, 3, 4 - thiadiazole and triazole derivatives, their preparation and use
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The invention relates to synthesis of a novel arylamine substituted-1,2,3,4-thiatriazole derivative (I) and an application of the derivative as a disease-resistant plant activator. As proved by activity study, the series of compounds has good prevention and control effects on various plant diseases.
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- 3-[(E)-(acridin-9′-ylmethylidene)amino]-1-substituted thioureas and their biological activity
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This paper describes the synthesis of a novel series of acridine thiosemicarbazones through a two-step reaction between various isothiocyanates and hydrazine followed by treatment with acridin-9-carbaldehyde. The properties of this series of seven new derivatives are studied using NMR and biochemical techniques, and the DNA-binding properties of the compounds are determined using spectrophotometric studies (UV–vis absorption, fluorescence, and circular/linear dichroism) and viscometry. The binding constants K are estimated as being in the range of 2.2 to 7.8?×?104?M??1 and the percentage of hypochromism was found to be 22.11–49.75% (from UV–vis spectral titration). Electrophoretic experiments prove that the novel compounds demonstrate moderate inhibitory effects against Topo I activity at a concentration of 60?×?10??6?M.
- Be?ka, Michal,Vilková, Mária,Salem, Othman,Ka?párková, Jana,Brabec, Viktor,Ko?urková, Mária
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p. 234 - 241
(2017/03/23)
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- PH-Regulated Nonelectrogenic Anion Transport by Phenylthiosemicarbazones
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Gated ion transport across biological membranes is an intrinsic process regulated by protein channels. Synthetic anion carriers (anionophores) have potential applications in biological research; however, previously reported examples are mostly nonspecific
- Howe, Ethan N. W.,Busschaert, Nathalie,Wu, Xin,Berry, Stuart N.,Ho, Junming,Light, Mark E.,Czech, Dawid D.,Klein, Harry A.,Kitchen, Jonathan A.,Gale, Philip A.
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supporting information
p. 8301 - 8308
(2016/07/16)
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- Design, synthesis and biological evaluation of thiosemicarbazones, hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance
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There is a constant need for new therapies against multidrug resistant (MDR) cancer. An attractive strategy is to develop chelators that display significant antitumor activity in multidrug resistant cancer cell lines overexpressing the drug efflux pump P-glycoprotein. In this study we used a panel of sensitive and MDR cancer cell lines to evaluate the toxicity of picolinylidene and salicylidene thiosemicarbazone, arylhydrazone, as well as picolinylidene and salicylidene hydrazino-benzothiazole derivatives. Our results confirm the collateral sensitivity of MDR cells to isatin-β-thiosemicarbazones, and identify several chelator scaffolds with a potential to overcome multidrug resistance. Analysis of structure-activity-relationships within the investigated compound library indicates that NNS and NNN donor chelators show superior toxicity as compared to ONS derivatives regardless of the resistance status of the cells.
- Pape, Veronika F.S.,Tóth, Szilárd,Füredi, András,Szebényi, Kornélia,Lovrics, Anna,Szabó, Pál,Wiese, Michael,Szakács, Gergely
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p. 335 - 354
(2016/05/19)
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- Synthesis of thiophene-thiosemicarbazone derivatives and evaluation of their in vitro and in vivo antitumor activities
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A series of thiophene-2-thiosemicarbazones derivatives (5-14) was synthesized, characterized and evaluated for their antitumor activity. They were tested in vitro against human tumor cell lines through the colorimetric method. The results revealed that compounds 7 and 9 were the most effective in inhibiting 50% of the cell growth after 48 h of treatment. As compound 7 showed a potent antiproliferative profile, it has been chosen for further studies in 786-0 cell line by flow cytometry. Treatments with compound 7 (50 μM) induced early phosphatidylserine exposure after 18 h of exposure and this process progressed phosphatidylserine exposure with loss of cell membrane integrity after 24 h of treatment, suggesting a time-dependent cell death process. Regarding the cell cycle profile, no changes were observed after treatment with compound 7 (25 μM), suggesting a mechanism of cell death independent on the cell cycle. The in vivo studies show that compound 7 possess low acute toxicity, being the doses of 30-300 mgKg-1 chosen for studies in Ehrlich solid tumor model in mice. All doses were able to inhibit tumor development being the lowest one the most effective. Our findings highlight thiophene-2-thiosemicarbazones as a promising class of compounds for further studies concerning new anticancer therapies.
- De Oliveira, Jamerson Ferreira,Da Silva, Anekécia Lauro,Vendramini-Costa, Débora Barbosa,Da Cruz Amorim, Cezar Augusto,Campos, Júlia Furtado,Ribeiro, Amélia Galdino,De Moura, Ricardo Olímpio,Neves, Jorge Luiz,Ruiz, Ana Lúcia Tasca Gois,De Carvalho, Jo?o Ernesto,Alves De Lima, Maria Do Carmo
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p. 148 - 156
(2015/10/29)
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- Thiosemicarbazide, a fragment with promising indolamine-2,3-dioxygenase (IDO) inhibition properties
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With the aim to explore the interest of the thiosemicarbazide scaffold for the inhibition of the indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target for anticancer immunotherapy, a series of 32 phenylthiosemicarbazide derivatives was prepared and their IDO inhibition evaluated. Our study demonstrated that among these derivatives, compound 14 characterized with a 4-cyanophenyl group on the thiosemicarbazide was the more potent IDO inhibitor in this series being endowed with an IC50 of 1.2 μM. The SAR depicted showed that substitution in the 3- and 4-position relative to the phenylthiosemicarbazide are very promising whereas substitution in the 2-position always leads to less potent or inactive derivatives. In fact the study highlighted a novel interesting scaffold for IDO inhibition for further development.
- Serra, Silvia,Moineaux, Laurence,Vancraeynest, Christelle,Masereel, Bernard,Wouters, Johan,Pochet, Lionel,Frédérick, Rapha?l
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- Synthesis and fungicidal activities of some 2-substituted arylamino-5-(2′-furyl)-1,3,4-thiadiazolo[3,2-c]thiazoles and 5-substituted aryl-2-substituted arylamino-1,3,4-thiadiazolo[3,2-c]thiazoles
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Several 2-substituted arylamino-5-(2′-furyl)-1,3,4-thiadiazolo[3,2-c] thiazoles have been synthesised by cyclisation of 3-substituted aryl thiocarbanilido-2-(2′-furyl)thiazolidin-4-ones with cone. H 2SO4 with constant stirring in cold and 5-substituted aryl-2-substituted arylamino-1,3,4-thiadiazolo[3,2-c]thiazoles have been synthesised by the cyclisation of 2-substituted aryl-3-substituted arylthiourido-thiazolidin-4-ones with cone. H2SO4 with constant stirring in cold and screened for their antifungal activities against Helminthosporium oryzae and Cephalosporium sacchari.
- Tiwari, Shailendra,Nizamuddin
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p. 679 - 683
(2013/07/26)
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- Augmentation of GABAergic neurotransmission by novel N-(substituted)-2-[4- (substituted)benzylidene]hydrazinecarbothioamides - A potential anticonvulsant approach
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New N-(substituted)-2-[4-(substituted)benzylidene]hydrazinecarbothioamides were designed, synthesized and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity was established in three seizure models i.e. MES, scMET and 6 Hz model. The most active compound was N-(4-methoxyphenyl)-2-[4-(4-methylphenoxy) benzylidene]hydrazinecarbothioamide PT 30 which showed 100% protection in both MES and 6 Hz test. Compound PT 30 showed protection at three different time points in 6 Hz test at a dose of 100 mg/kg. Compound 2-[4-(4-Chlorophenoxy)benzylidene]-N-cyclohexylhydrazine carbothioamide PT 4 was also found to be active in both MES and 6 Hz test. Titled compounds exhibited good binding properties with epilepsy molecular targets GABA (A) delta and GABA (A) alpha-1 receptors, in LGA based flexible docking studies. Compounds PT 30 and PT 4 were found to elevate γ-aminobutyric acid (GABA) levels in the midbrain and medulla oblongata regions of rat brain. A computational study was carried out for calculation of pharmacophore pattern and prediction of pharmacokinetic properties.
- Tripathi, Laxmi,Kumar, Praveen
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p. 477 - 487
(2013/07/19)
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- Synthesis and biological activities of novel artemisinin derivatives as cysteine protease falcipain-2 inhibitors
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A series of novel artemisinin derivatives were synthesized from artemisinin and different anilines. All compounds were obtained as β-isomers. The target compounds were evaluated for inhibition activity against Plasmodium falciparum falcipain-2 in vitro, and most of them exhibited potent inhibition in the low micromolar range and proved to be new types of falcipain-2 inhibitors.
- Liu, Yang,Lu, Wei-Qiang,Cui, Kun-Qiang,Luo, Wei,Wang, Jian,Guo, Chun
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p. 1525 - 1531
(2013/03/14)
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- Metal self-recognition: A pathway to control the formation of dihelicates and mesocates
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We have studied the factors that affect the formation of different metallosupramolecular architectures by metal direct self-assembly. A synthetic route has been developed to obtain mesocates or dihelicates selectively. For this purpose a series of five bi
- Martinez-Calvo, Miguel,Romero, Maria J.,Pedrido, Rosa,Gonzalez-Noya, Ana M.,Zaragoza, Guillermo,Bermejo, Manuel R.
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supporting information
p. 13395 - 13404
(2013/01/15)
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- Discovery of orally active pyrazoloquinolines as potent PDE10 inhibitors for the management of schizophrenia
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A series of pyrazoloquinoline analogs have been synthesized and shown to bind to PDE10 with high affinity. From the SAR study and our lead optimization efforts, compounds 16 and 27 were found to possess potent oral antipsychotic activity in the MK-801 induced hyperactive rat model.
- Yang, Shu-Wei,Smotryski, Jennifer,McElroy, William T.,Tan, Zheng,Ho, Ginny,Tulshian, Deen,Greenlee, William J.,Guzzi, Mario,Zhang, Xiaoping,Mullins, Deborra,Xiao, Li,Hruza, Alan,Chan, Tze-Ming,Rindgen, Diane,Bleickardt, Carina,Hodgson, Robert
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scheme or table
p. 235 - 239
(2012/02/16)
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- Microwave-assisted synthesis and antibacterial activity of novel chenodeoxycholic acid thiosemicarbazone derivatives
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A rapid and efficient method for the synthesis of novel chenodeoxycholic acid thiosemicarbazone derivatives under solvent-free conditions using microwave irradiation is reported. Ten novel compounds have been synthesised in good yields. Their structures were elucidated by 1H NMR, IR, ESI-MS spectra and elemental analysis. Preliminary results showed that some of these compounds possess inhibitory effects against S. typhimurium and E. coli.
- Qiu, Liying,Shi, Zhichuan,Mei, Qinggang,Zhao, Zhigang
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experimental part
p. 456 - 459
(2011/11/06)
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- Synthesis of new hyodeoxycholic acid thiosemicarbazone derivatives under solvent-free conditions using microwave
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An efficient and simple method for synthesis of new hyodeoxycholic acid thiosemicarbazone derivatives under solvent-free conditions using microwave has been developed. Its main advantages are short reaction times, good conversions and the environmentally friendly nature of the process. The preliminary results indicate that some of these compounds possess inhibitory effects against E. coli.
- Shi, Zhi Chuan,Zhao, Zhi Gang,Liu, Xing Li,Chen, Yu
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experimental part
p. 405 - 408
(2012/01/05)
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- Synthesis, anticonvulsant and toxicity screening of thiazolyl-thiadiazole derivatives
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Various thiazole-substituted thiadiazole derivatives (7a-t) were designed and synthesized using substituted acetophenones and substituted anilines as starting materials. Thiazole and thiadiazole moieties being anticonvulsants were clubbed together to get the titled compounds and their in vivo anticonvulsant screening were performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Three compounds 7i, 7l and 7n were found to be potent in both the screens with comparable ED50 and better TD50 values than some standard drugs. These compounds were also found to exert lesser toxic effects on liver.
- Siddiqui, Nadeem,Ahsan, Waquar
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experimental part
p. 261 - 268
(2012/02/13)
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- Isatin-β-thiosemicarbazones as potent herpes simplex virus inhibitors
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A series of isatin-β-thiosemicarbazones have been designed and evaluated for antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in a plaque reduction assay. Their cytotoxicity was examined using human rhabdomyosarcoma cells (RD cells). Several derivatives of isatin-β-thiosemicarbazone exhibited significant and selective antiviral activity with low cytotoxicity. It was found that the thiourea group at thiosemicarbazone and the NH functionality at isatin were essential for their antiherpetic activity. The synthesis and structure-activity relationship studies are presented.
- Kang, Iou-Jiun,Wang, Li-Wen,Hsu, Tsu-An,Yueh, Andrew,Lee, Chung-Chi,Lee, Yen-Chun,Lee, Ching-Yin,Chao, Yu-Sheng,Shih, Shin-Ru,Chern, Jyh-Haur
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p. 1948 - 1952
(2011/05/04)
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- A sequentially assembled grid composed of supramolecular meso-helical nodes
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A unique case of a grid-of-mesocates sequentially assembled by supramolecular cobalt(ii) meso-helical units connected through hydrogen bonding is reported. The Royal Society of Chemistry 2011.
- Martinez-Calvo, Miguel,Pedrido, Rosa,Gonzalez-Noya, Ana M.,Romero, Maria J.,Cwiklinska, Magdalena,Zaragoza, Guillermo,Bermejo, Manuel R.
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supporting information; experimental part
p. 9633 - 9635
(2011/10/09)
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- Solvent-free synthesis of indole-based thiosemicarbazones under microwave irradiation
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A rapid, effi cient and environmentally friendly methodology has been developed for the synthesis of indole-3-carboxaldehyde thiosemicarbazones by using aluminum oxide as the solid support under microwave assisted solvent-free conditions. Compared with the conventional heating method, this method gave the target products in good yield.
- Liu, Lingling,Yang, Jie,Zhao, Zhigang,Shi, Peiyu,Liu, Xingli
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experimental part
p. 57 - 60
(2010/05/19)
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- Triazole incorporated thiazoles as a new class of anticonvulsants: Design, synthesis and in vivo screening
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Various 3-[4-(substituted phenyl)-1,3-thiazol-2-ylamino]-4-(substituted phenyl)-4,5-dihydro-1H-1,2,4-triazole-5-thiones (7a-t) were designed keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity. Thiazole and triazole moieties being anticonvulsants were clubbed together to get the titled compounds and their in vivo anticonvulsant screening were performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Two compounds 7d and 7f showed significant anticonvulsant activity in both the screens with ED50 values 23.9?mg/kg and 13.4?mg/kg respectively in MES screen and 178.6?mg/kg and 81.6?mg/kg respectively in scPTZ test. They displayed a wide margin of safety with Protective index (PI), median hypnotic dose (HD50) and median lethal dose (LD50) much higher than the standard drugs.
- Siddiqui, Nadeem,Ahsan, Waquar
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experimental part
p. 1536 - 1543
(2010/06/16)
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- Microwave-assisted synthesis of new steroidal thiosemicarbazones derived from methyl 3-oxocholanate under solvent-free conditions
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A series of novel steroidal thiosemicarbazones derived from methyl 3-oxocholanate were synthesised in good yields via microwave irradiation under solvent-free conditions. The structures of the compounds were confirmed by spectroscopic data. Compared to the conventional method, microwave irradiation was a fast and simple method. These compounds were tested for antibacterial activity against S. aureus, S. pyogenes, and E. coli bacteria.
- Zhao, Zhigang,Liu, Xingli,Liu, Lingling,Li, Guohua
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experimental part
p. 455 - 458
(2010/12/24)
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- Synthesis of novel alkoxycarbonyl thiosemicarbazide molecular tweezers derived from deoxycholic acid under microwave irradiation
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A series of novel 12α-alkoxycarbonyl thiosemicarbazide molecular tweezers based on 3α-(1-naphthoyl) deoxycholic acid methyl ester were synthesised under microwave irradiation. Their structures were characterised by 1H NMR, IR, MS spectra and elemental analysis. Their chiral recognition properties for the methyl esters of amino acids were investigated. The preliminary results showed that these molecular tweezers have good enantioselective recognition for D/L-amino acid methyl esters.
- Chen, Yu,Zhao, Zhi Gang,Liu, Xing Li,Shi, Zhi Chuan
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scheme or table
p. 416 - 420
(2010/12/19)
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- A series of α-heterocyclic carboxaldehyde thiosemicarbazones inhibit topoisomerase IIα catalytic activity
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A series of novel thiosemicarbazone derivatives bearing condensed heterocyclic carboxaldehyde moieties were designed and synthesized. Among them, TSC24 exhibited broad antiproliferative activity in a panel of human tumor cells and suppressed tumor growth in mice. The mechanism research revealed that TSC24 was not only an iron chelator but also a topoisomerase IIα catalytic inhibitor. Its inhibition on topoisomerase IIα was due to direct interaction with the ATPase domain of topoisomerase IIα which led to the block of ATP hydrolysis. Molecular docking predicted that TSC24 might bind at the ATP binding site, which was confirmed by the competitive inhibition assay. These results about the mechanisms involved in the anticancer activities of thiosemicarbazones will aid in the rational design of novel topoisomerase II-targeted drugs and will provide insights into the discovery and development of novel cancer therapeutics based on the dual activity to chelate iron and to inhibit the catalytic activity of topoisomerase IIα.
- Huang, He,Chen, Qin,Ku, Xin,Meng, Linghua,Lin, Liping,Wang, Xiang,Zhu, Caihua,Wang, Yi,Chen, Zhi,Li, Ming,Jiang, Hualiang,Chen, Kaixian,Ding, Jian,Liu, Hong
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experimental part
p. 3048 - 3064
(2010/09/05)
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- Discovery of novel GSK-3β inhibitors with potent in vitro and in Vivo activities and excellent brain permeability using combined ligand- and structure-based virtual screening
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Dysregulation of glycogen synthase kinase (GSK-3β) is implicated in the pathophysiology of many diseases, including type-2 diabetes, stroke, Alzheimers, and others. A multistage virtual screening strategy designed so as to overcome known caveats arising from the considerable flexibility of GSK-3β yielded, from among compounds in our in-house database and two commercial databases, new GSK-3β inhibitors with novel scaffold structures. The two most potent and selective validated hits, a 2-anilino-5-phenyl-1,3,4- oxadiazole (24) and a phenylmethylene hydantoin (28), both exhibited nanomolar affinity and selectivity over CDK2 and were potent enough for direct in vivo validation. Both were able to cause significant increases in liver glycogen accumulation in dose-dependent fashion. One also exhibited excellent blood-brain barrier permeability, the other adequate for a lead compound. Analogues of the oxadiazole 24 were synthesized to experimentally corroborate or rule out ligand-bound structures arising from docking studies. SAR results supported one docking study among a number of alternatives.
- Khanfar, Mohammad A.,Hill, Ronald A.,Kaddoumi, Amal,El Sayed, Khalid A.
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experimental part
p. 8534 - 8545
(2011/02/26)
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- Synthesis, characterization and spectral evaluation of some new substituted thiosemicarbazides and thiosemicarbazones
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A new series of substituted thiosemicarbazides and substituted thiosemicarbazones containing different functional groups, thiosemicarbazones have been synthesized by the condensation reaction between newly synthesized substituted thiosemicarbazides with s
- Pareek, Alok K.,Joseph,Seth, Daya S.
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experimental part
p. 1549 - 1552
(2011/10/12)
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- N-(Acetamido)thiourea based simple neutral hydrogen-bonding receptors for anions
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N-(Acetamido)-N′-phenylthioureas (4-6) were found to be efficient anion receptors with higher anion affinity than their N-benzamido-N′- phenylthiourea counterparts (1 and 2). The N′-phenylthiourea moiety in 4-6 was shown to be the chromophore with an absorption maximum at ca. 270 nm. It was found that, in the presence of anions, the absorption at ca. 270 nm of 4-6 (except 5f) in acetonitrile (MeCN) was blue shifted and enhanced while a red-shifted shoulder appeared at ca. 295 nm, together with an isosbestic point at ca. 240 nm. The 1:1 anion binding constants of 4-6, for example at 10 6-107 M-1 order of magnitude for AcO - in MeCN, were found to be higher than those of 1 and 2, although the acidity of the thioureido -NH protons in 4-6 is lower than that in 1 and 2. 1H NMR data indicates that the N-N single bond in 4-6 is twisted but less than that in 1 and 2. A conformation change at the N-N single bond of 4-6 was suggested to occur upon anion binding which leads to a planar hydrogen-bonding network in the anion binding complex in which a charge transfer takes place with the N-acyl moiety being the electron acceptor. Variations in the CD signals of a proline derivative 6 bearing a chiral center in the N-amido moiety provide direct evidence for this conformation change upon its binding with anions in MeCN. The amplified effect of substituent X at the N′-phenyl ring of 5 on the anion binding constant supports the conclusion of anion-binding switched charge transfer in the anion binding complex. 1H NMR and absorption titrations for 5 indicated that the anion-receptor interaction was of a hydrogen-bonding nature until the N′-phenyl substituent X is as electron-withdrawing as m-CF3 (5e). With X being the more electron-withdrawing p-NO2 (5f), deprotonation of the thioureido -NH occurs in the presence of anion. Results reported here confirm that N-amidothioureas derived from both N-aliphatic and N-aromatic amides can in general be a family of efficient hydrogen-bonding receptors, with the aliphatic N-amido derivatives being more efficient. This provides a wider structural diversity for designing thiourea-based functional molecules such as anion receptors and organocatalysts. Preliminary experiments confirm that 6 could catalyse efficiently the reduction of nitrostyrene in CH2Cl2 and MeCN.
- Liu, Wen-Xia,Yang, Rui,Li, Ai-Fang,Li, Zhao,Gao, Yu-Feng,Luo, Xing-Xing,Ruan, Yi-Bin,Jiang, Yun-Bao
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experimental part
p. 4021 - 4028
(2009/12/06)
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- Synthesis, activity, and pharmacophore development for isatin-β- thiosemicarbazones with selective activity toward multidrug-resistant cells
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We have recently identified a new class of compounds that selectively kill cells that express P-glycoprotein (P-gp, MDR1), the ATPase efflux pump that confers multidrug resistance on cancer cells. Several isatin-β- thiosemicarbazones from our initial stud
- Hall, Matthew D.,Salam, Noeris K.,Hellawell, Jennifer L.,Fales, Henry M.,Kensler, Caroline B.,Ludwig, Joseph A.,Szakács, Gergely,Hibbs, David E.,Gottesman, Michael M.
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scheme or table
p. 3191 - 3204
(2010/03/31)
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- 5-Nitrofuran-2-yl derivatives: Synthesis and inhibitory activities against growing and dormant mycobacterium species
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Eighteen 5-nitrofuran-2-yl derivatives were prepared by reacting 5-nitro-2-furfural with various (sub)phenyl/pyridyl thiosemicarbazide using microwave irradiation. The compounds were tested for their in vitro activity against tubercular and various non-tubercular mycobacterium species in log-phase and 6-week-starved cultures. Compound N-(3,5-dibromopyridin-2-yl)-2-((5-nitrofuran-2-yl)methylene)hydrazinecarbothioamide (4r) was found to be the most potent compound (MIC: 0.22 μM) and was 3 times more active than standard isoniazid (INH) and equally active as rifampicin (RIF) in log-phase culture of Mycobacterium tuberculosis H37Rv. In starved M. tuberculosis H37Rv, 4r inhibited with MIC of 13.9 μM and was found to be 50 times more active than INH and slightly more active than RIF.
- Sriram, Dharmarajan,Yogeeswari, Perumal,Dhakla, Prathiba,Senthilkumar, Palaniappan,Banerjee, Debjani,Manjashetty, Thimmappa H.
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body text
p. 1152 - 1154
(2009/08/07)
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- Synthesis and antituberculosis activity of 5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone derivatives
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New series of 5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones 3a-t, 1-methyl-5-methyl/trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones 4a-y and 5-trifluoromethoxy-1-morpholinomethyl-1H-indole-2,3-dione 3-thiosemicarbazones 5a-m were synthesized. The structures of the synthesized compounds were confirmed by spectral data and elemental analysis. The new 5-methyl/trifluoromethoxy-1H-indole-2,3-dione derivatives, along with previously synthesized 5-methyl-1H-indole-2,3-dione 3-thiosemicarbazones 6a-l, were evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv. 5-Methyl-1H-indole-2,3-dione 3-thiosemicarbazones (3b, 3d, 3f, 6c, 6d, and 6f), 5-trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazones (3q-s) and 5-trifluoromethoxy-1-morpholinomethyl-1H-indole-2,3-dione 3-thiosemicarbazones (5e and 5j-l) were found to be the most potent inhibitors of M. tuberculosis growth described in this study.
- Guezel, Oezlen,Karali, Nilguen,Salman, Aydin
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experimental part
p. 8976 - 8987
(2009/04/11)
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- NOVEL HSP90 INHIBITOR
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Disclosed is a triazole derivative represented by the general formula (1) below or a pharmacologically acceptable salt thereof. Also disclosed are a prodrug of such a triazole derivative and an HSP90 inhibitor containing any one of them as an active constituent. (1) (In the formula, X represents a halogen atom, an optionally substituted alkyl group, an optionally substituted alkenyl group or the like; Y represents a mercapto group, a hydroxyl group, an optionally substituted sulfonyl group, an optionally substituted amino group or the like; and R represents an optionally substituted aryl or amino group or the like.)
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