- Synthesis, in vitro thymidine phosphorylase activity and molecular docking study of thiadiazole bearing isatin analogs
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A series of seventeen analogs (1─17) were synthesized and characterized through different spectroscopic techniques such as 1H, 13CNMR, HR-EI-MS and were evaluated for in vitro thymidine phosphorylase inhibition. All compounds showed excellent to good thymidine phosphorylase activity having IC50 value ranging between 4.10 ± 0.20 and 54.60 ± 1.40?μM when compared with standard drug 7-deazaxanthine (IC50 = 38.68 ± 1.12?μM). Among the series, compounds 1 (IC50 = 8.30 ± 0.30?μM), 6 (IC50 = 6.30 ± 0.10?μM), 11 (IC50 = 8.40 ± 0.30?μM) and 16 (IC50 = 4.10 ± 0.20?μM) were found more potent. Potent compounds were further subjected to molecular docking study to identify their interactions with the active site of amino acid. Structure activity relationship was done for all analogs mostly based on substitution pattern on phenyl and isatin rings. Graphic abstract: [Figure not available: see fulltext.]
- Ullah, Hayat,Liaqat, Anjum,Khan, Qudrat Ullah,Taha, Muhammad,Khan, Fahad,Rahim, Fazal,Uddin, Imad,Rehman, Zia Ur
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p. 213 - 224
(2021/09/09)
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- Synthesis and antimicrobial activities of thiadiazole containing quinoline derivatives
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A novel series of 1-[(substituted 2-chloroquinolin-3-yl)methylidene]-3-[substituted-5-phenyl-1,3,4-thiadiazol-2-yl] thioureas have been synthesized by acid catalyzed reaction between the 1-(5-substitued phenyl-1,3,4-thiadiazol-2-yl) thioureas and 6-substi
- D'Souza, Vineetha Telma,Dayananda, P.,Nayak, Janardhana
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p. 633 - 638
(2021/09/28)
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- Diversity-Oriented Synthesis of 1,2,4-Triazols, 1,3,4-Thiadiazols, and 1,3,4-Selenadiazoles from N-Tosylhydrazones
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The diversity-oriented synthesis of 1,2,4-triazols, 1,3,4-thiadiazols, and 1,3,4-selenadiazoles from N-tosylhydrazones was developed, and the reactions were general for a wide range of substrates, in which NH2CN, KOCN, KSCN, and KSeCN were used as odorless sources. Two different pathways were proposed, and N-tosylhydrazonoyl chlorides were formed in situ in the presence of NCS.
- Wei, Zeyang,Zhang, Qi,Tang, Meng,Zhang, Siyu,Zhang, Qian
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supporting information
p. 4436 - 4440
(2021/05/26)
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- N-(5-phenyl-1, 3, 4-thiadiazole-2-yl) benzamide compound
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The invention belongs to the technical field of medicines, relates to a compound with antitumor activity and a specific chemical structure, and in particular relates to an N-((6, 7-dimethoxyquinoline-4-yl) oxy) methyl)-N-(5-phenyl-1, 3, 4-thiadiazole-2-yl) benzamide compound and a preparation method and an application thereof. The structural general formula of the compound is shown in the specification, wherein an R group is mono-substituted or double-substituted phenyl, fluorophenyl, chlorphenyl, bromophenyl, benzyl, benzyloxy, benzene nitro or trifluoromethyl substituted at 2-position, 3-position or 4-position. Pharmacological studies show that the compound provided by the invention has a relatively remarkable proliferation inhibition effect on HER-2 positive breast cancer cells SK-Br-3, the effect is obviously superior to that of HER-2 negative breast cancer cells MCF-7, the compound can be used for preparing antitumor drugs, and a new way is opened up for deep research and development of tumor drugs in the future. The preparation method provided by the invention is simple and feasible, relatively high in yield and easy for large-scale production.
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Paragraph 0051; 0057; 0111-0113
(2021/06/09)
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- 1,2,4-Triazole-conjugated 1,3,4-thiadiazole hybrid scaffolds: A potent ameliorant of carrageenan-induced inflammation by lessening proinflammatory mediators
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Inflammation acts as an alarming signal for the progression of various biological complications. Various reports in the literature have revealed that heterocycle-containing synthetic compounds have a restorative capability against acute and chronic inflammatory stages. In the current study, we synthesized a series of 1,2,4-triazole-conjugated 1,3,4-thiadiazole hybrid scaffolds and evaluated their impacts against carrageenan-induced paw edema and proinflammatory markers in Wistar rats. Further, 3D QSAR study (three-dimensional quantitative structure–activity relationships), ADMET (absorption, distribution, metabolism, and excretion) profiling, and docking studies were performed to determine the possible mechanism of the action of the derivatives. The study shows that the most active derivatives, 13f and 13g, have optimal logP, a higher anti-inflammatory activity score, and poor metabolism at various sites of cytochrome P450. The docking studies recommended that the synthesized compounds have a similar affinity as the ligands A307, 63X, and S58 to interact with tumor necrosis factor-α, COX-1, and COX-2. So, these molecules will definitely hold a promise for the future drug development initiative.
- Pathak, Prateek,Shukla, Parjanya K.,Naumovich, Vladislav,Grishina, Maria,Verma, Amita,Potemkin, Vladimir
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- 1,3,4-Thiadiazole-Containing Azo Dyes: Synthesis, Spectroscopic Properties and Molecular Structure
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Three series of azo dyes derived from 2-amino-5-aryl-1,3,4-thiadiazoles and aniline, N,N-dimethylaniline and phenol were synthesized in high yields by a conventional diazotization-coupling sequence. The chemical structures of the prepared compounds were confirmed by 1H-NMR, 13C-NMR, IR, UV-Vis spectroscopy, mass spectrometry and elemental analysis. In addition, the X-ray single crystal structure of a representative azo dye was presented. For explicit determination of the influence of a substituent on radiation absorption in UV-Vis range, time-dependent density functional theory calculations were performed.
- Kudelko, Agnieszka,Olesiejuk, Monika,Luczynski, Marcin,Swiatkowski, Marcin,Sieranski, Tomasz,Kruszynski, Rafal
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- Design and development of 1,3,5-triazine-thiadiazole hybrids as potent adenosine A2A receptor (A2AR) antagonist for benefit in Parkinson's disease
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Various studies showed adenosine A2A receptors (A2ARs) antagonists have profound therapeutic efficacy in Parkinsons Disease (PD) by improving dopamine transmission, thus being active in reversing motor deficits and extrapyramidal symptoms related to the disease. Therefore, in the presents study, we have showed the development of novel 1,3,5-triazine-thiadiazole derivative as potent A2ARs antagonist. In the radioligand binding assay, these molecules showed excellent binding affinity with A2AR compared to A1R, with significant selectivity. Results suggest, compound 7e as most potent antagonist of A2AR among the tested series. In docking analysis with A2AR protein model, compound 7e found to be deeply buried into the cavity of receptor lined via making numerous interatomic contacts with His264, Tyr271, His278, Glu169, Ala63, Val84, Ile274, Met270, Phe169. Collectively, our study demonstrated 1,3,5-triazine-thiadiazole hybrid as a highly effective scaffold for the design of new A2A antagonists.
- Agnihotri, Amol Kumar,Bhat, Hans Raj,Giri, Sabeena,Masih, Anup,Pandey, Nidhi,Shrivastava, Jitendra Kumar,Singh, Saumya,Singh, Udaya Pratap
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- N-thiadiazole-4-hydroxy-2-quinolone-3-carboxamides bearing heteroaromatic rings as novel antibacterial agents: Design, synthesis, biological evaluation and target identification
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Due to the occurrence of antibiotic resistance, bacterial infectious diseases have become a serious threat to public health. To overcome antibiotic resistance, novel antibiotics are urgently needed. N-thiadiazole-4-hydroxy-2-quinolone-3-carboxamides are a potential new class of antibacterial agents, as one of its derivatives was identified as an antibacterial agent against S. aureus. However, no potency-directed structural optimization has been performed. In this study, we designed and synthesized 37 derivatives, and evaluated their antibacterial activity against S. aureus ATCC29213, which led to the identification of ten potent antibacterial agents with minimum inhibitory concentration (MIC) values below 1 μg/mL. Next, we performed bacterial growth inhibition assays against a panel of drug-resistant clinical isolates, including methicillin-resistant S. aureus, and cytotoxicity assays with HepG2 and HUVEC cells. One of the tested compounds named 1-ethyl-4-hydroxy-2-oxo-N-(5-(thiazol-2-yl)-1,3,4-thiadiazol-2-yl)-1,2-dihydroquinoline-3-carboxamide (g37) showed 2 to 128-times improvement compared with vancomycin in term of antibacterial potency against the tested strains (MICs: 0.25–1 μg/mL vs. 1–64 μg/mL) and an optimal selective toxicity (HepG2/MRSA, 110.6 to 221.2; HUVEC/MRSA, 77.6–155.2). Further, comprehensive evaluation indicated that g37 did not induce resistance development of MRSA over 20 passages, and it has been confirmed as a bactericidal, metabolically stable, orally active antibacterial agent. More importantly, we have identified the S. aureus DNA gyrase B as its potential target and proposed a potential binding mode by molecular docking. Taken together, the present work reports the most potent derivative of this chemical series (g37) and uncovers its potential target, which lays a solid foundation for further lead optimization facilitated by the structure-based drug design technique.
- Xue, Wenjie,Li, Xueyao,Ma, Guixing,Zhang, Hongmin,Chen, Ya,Kirchmair, Johannes,Xia, Jie,Wu, Song
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- Pyridine and nitro-phenyl linked 1,3,4-thiadiazoles as MDR-TB inhibitors
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In the present study, a series of substituted 1,3,4-thiadiazole derivatives 4(a–o), 5(a–m) and 6(a–j) were synthesized and characterized by IR, 1H NMR, 13C NMR and mass spectroscopic technique. The synthesized compounds were evaluate
- Patel, Harun,Jadhav, Harsha,Ansari, Iqrar,Pawara, Rahul,Surana, Sanjay
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- Synthesis and antiviral activity of some imidazo[1,2-b][1,3,4]thiadiazole carbohydrate derivatives
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Herein we describe the synthesis of imidazo[2,1-b][1,3,4]thiadiazoles from carbohydrates with D-ribo and D-xylo configuration. The antiviral activity of these compounds was tested against Junín virus (the etiological agent of Argentine hemorrhagic fever). The p-chlorophenyl derivatives showed antiviral activity in a range of micromolar concentration.
- Fascio, Mirta L.,Sepúlveda, Claudia S.,Damonte, Elsa B.,D'Accorso, Norma B.
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- Synthesis, structural characterization and computational study of NLO-responsive chromophores and second-order coefficients of thermally crosslinked polymers
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This paper emphasizes the preparation of nonlinear optical (NLO) responsive chromophores and their corresponding polymers. Initially, the carboxyl acid group-based precursors of the chromophores containing strong acceptors such as nitro-substituted thiazo
- Doddamani, Radha V.,Rachipudi, Padmeshwary S.,Pattanashetti, Nandini A.,Kariduraganavar, Mahadevappa Y.
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p. 15723 - 15735
(2019/10/19)
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- Silica catalyzed one pot synthesis of hybrid thiazolidin-4-one derivatives as anti-tubercular and anti-inflammatory agent by attenuating COX-2 pathway
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A novel series of a hybrid class of hybrid thiazolidin-4-one derivatives were designed and synthesized through one-pot catalytic synthesis. The reaction was catalyzed in the presence of silica-H2SO4(+6). The derivatives computational
- Pathak, Prateek,Shukla, Parjanya Kumar,Naumovich, Vladislav,Grishina, Maria,Potemkin, Vladimir,Verma, Amita
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p. 2725 - 2759
(2019/08/08)
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- Synthesis, in vitro and in silico Anti-Proliferative Studies of Novel Piperiene-Oxadiazole and Thiadiazole Analogs
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Piperine is a component of pepper which has earlier been reported as anticancer active compound. This work is emphasized on the design and synthesis of new hybrid piperine analogs by coupling piperine with the amine group of oxadiazoles and thiadiazoles.
- Amperayani,Parimi
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p. 2301 - 2307
(2020/01/08)
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- I2 Promoted Synthesis of 2-Aminothiadiazoles Employing KSCN as a Sulfur Source Under Metal-Free Conditions
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A new three-component strategy from aldehyde, p-toluenesulfonyl hydrazide and potassium thiocyanate for the synthesis of 2-aminothiadiazoles promoted by I2 under metal-free conditions has been described. Potassium thiocyanate was used as an odo
- Zhu, Fuyuan,Yan, Zhaohua,Ai, Chengmei,Wang, Yanmei,Lin, Sen
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supporting information
p. 6561 - 6565
(2019/10/22)
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- Synthesis and molecular simulation study of furoic peptidomimetic derivatives as potent aminopeptodase N inhibitors
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The aminopeptidase N (APN) plays a critical role in angiogenesis and is over-expressed in tumor cells. In this paper, we report the synthesis and enzyme inhibition assay of furoic peptidomimetic compounds. These new compounds exhibit potent inhibitory ability toward APN with IC50 values lying in the micromolar level. The binding mode of inhibitors in APN active site was explained by a molecular simulation study. These data reveal that ligand coordinating with the catalytic Zn-ion is very important for inhibitory activities.
- Gao, Min,He, Junhua,Xu, Weidong,Lai, Xiaoping,Liu, Fen,Tu, Guogang
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p. 123 - 127
(2018/03/25)
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- Spiro-heterocyclics: A convenient synthesis and antimicrobial activity of 3-(5- substituted phenyl-l,3,4-thiadiazole-2-yl)-5,8-dithiaspiro[3,4]octan-2-ones and 1,4-dithia-6-azaspiro[4,4]-nonan-7-ones
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A new series of novel 3-(5-substituted phenyl-l,3,4-thiadiazole-2-yl)-5,8-dithiaspiro[3,4]octan-2-ones and l,4-dithia-6- - azaspiro[4,4]nonan-7-ones have been synthesized from a common intermediate, in good yields. These compounds have been screened for t
- Tiwari, Shailendra
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p. 1416 - 1420
(2019/05/22)
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- Synthesis, in vitro α-glucosidase inhibitory potential and molecular docking study of thiadiazole analogs
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α-Glucosidase is a catabolic enzyme that regulates the body's plasma glucose levels by providing energy sources to maintain healthy functioning. 2-Amino-thiadiazole (1–13) and 2-amino-thiadiazole based Schiff bases (14–22) were synthesized, characterized by 1H NMR and HREI-MS and screened for α-glucosidase inhibitory activity. All twenty-two (22) analogs exhibit varied degree of α-glucosidase inhibitory potential with IC50 values ranging between 2.30 ± 0.1 to 38.30 ± 0.7 μM, when compare with standard drug acarbose having IC50 value of 39.60 ± 0.70 μM. Among the series eight derivatives 1, 2, 6, 7, 14, 17, 19 and 20 showed outstanding α-glucosidase inhibitory potential with IC50 values of 3.30 ± 0.1, 5.80 ± 0.2, 2.30 ± 0.1, 2.70 ± 0.1, 2.30 ± 0.1, 5.50 ± 0.1, 4.70 ± 0.2, and 5.50 ± 0.2 μM respectively, which is many fold better than the standard drug acarbose. The remaining analogs showed good to excellent α-glucosidase inhibition. Structure activity relationship has been established for all compounds. The binding interactions of these compounds were confirmed through molecular docking.
- Javid, Muhammad Tariq,Rahim, Fazal,Taha, Muhammad,Rehman, Haseeb Ur,Nawaz, Mohsan,wadood, Abdul,Imran, Syahrul,Uddin, Imad,Mosaddik, Ashik,Khan, Khalid Mohammed
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p. 201 - 209
(2018/04/02)
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- PhI-Catalyzed Intramolecular Oxidative Coupling Toward Synthesis of 2-Amino-1,3,4-Thiadizoles
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A highly efficient method for the synthesis of thiadiazole derivatives via intramolecular oxidative coupling of thiosemicarbazide, using the in situ generated hypervalent iodine(III) reagents is developed. The protocol can be carried out smoothly and provides a variety of thiadiazole derivatives in moderate to excellent yields. Graphical Abstract: A highly efficient method for the synthesis of thiadiazole derivatives via PhI-catalyzed intramolecular oxidative coupling of thiosemicarbazide has been developed.
- Han, Yingzhi,Sun, Yadong,Abdukader, Ablimit,Liu, Bifu,Wang, Duozhi
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p. 3486 - 3491
(2018/09/27)
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- Metal-free synthesis of 2-aminothiadiazoles via TBHP-Mediated oxidative C-S bond formation
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An efficient one-pot synthesis of 2-amino-1,3,4-thiadiazoles from easily available aldehydes and thiosemicarbazide using TBHP as an oxidant has been described. Notably, these reactions were carried out at room temperature using ethanol as solvent. This is the first example for one-pot synthesis of 2-amino-1,3,4-thiadiazole derivatives from aldehydes. This new synthetic methodology provides a simple procedure utilizing a safer oxidizing system that affords the target products in mild reaction condition with satisfactory yields and wide substrate scope.
- Hatvate, Navnath T.,Ghodse, Shrikant M.,Telvekar, Vikas N.
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supporting information
p. 285 - 290
(2018/02/09)
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- 2-(4-nitrophenyl)-6-ferrocenyl-imidazo[2,1-b]-1,3,4-thiadiazole preparation method
-
The present invention discloses a 2-(4-nitrophenyl)-6-ferrocenyl-imidazo[2,1-b]-1,3,4-thiadiazole preparation method, which comprises: carrying out stirring mixing on 2-amino-5-(4-nitrophenyl)-1,3,4-thiadiazole, alpha-bromo-acetylferrocene and ethanol; pl
- -
-
Paragraph 0021; 0025; 0026; 0036; 0046
(2018/01/12)
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- Efficient three-component synthesis of N-alkyl-3, 6-diaryl-[1, 2, 4]triazolo[4, 3-b][1, 2, 4]triazin-7-amines under solvent-free condition
-
A simple, efficient and environment-friendly approach is described for the synthesis of N-alkyl-3, 6-diaryl-[1, 2, 4]triazolo[4, 3-b][1, 2, 4]triazin-7-amines based on three-component reaction between 5-aryl-4H-1, 2, 4-triazole-3, 4-diamine, isocyanide and aldeyhde under solvent-free condition. The products are obtained in moderate to good yields and are in a state of high purity.
- Azimi, Sara,Soheilizad, Mehdi,Zonouzi, Afsaneh,Mahdavi, Mohammad
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p. 293 - 300
(2017/12/06)
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- Cyclization–oxidation of Benzylidenehydrazinecarbothioamides by FeCl3.6H2O or ZnCl2.6H2O Catalysts and Synthesis of New 1,3,4-Thiadiazolo-[3,2- α]Pyrimidines
-
We report new method for preparation of 2-amino-5-aryl-1,3,4-thiadiazoles by reaction of arylaldehyde with thiosemicarbazide and in the next step via cyclization of 2-aryl hydrazinecarbothioamide in the presence of ZnCl2.6H2O or FeCl3.6H2O. Also, in this research, new substituted 1,3,4-thiadiazolo-[3,2-α]pyrimidines were synthesized by the reaction of 2-amino-5-aryl-1,3,4-thiadiazoles derivatives with DMAD or DEAD in the presence of K2CO3 under reflux conditions. The FT-IR, 1H-NMR, 13C-NMR, elemental analysis and single- crystal X-ray analysis confirm the structures of the products.
- Darehkordi, Ali,Zarezadeh Abarqouei, Behnam,Rahmani, Fariba
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p. 1872 - 1879
(2017/05/29)
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- Thiadiazolodiazepine analogues as a new class of neuromuscular blocking agents: Synthesis, biological evaluation and molecular modeling study
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The synthesis, biological evaluation and molecular modeling study of 6,7-dihydro-[1,3,4] thiadiazolo[3,2-a][1,3]diazepine analogues as new class of neuromuscular blocking agents are described. The new compounds act via competitive mechanism with ACh which
- El-Subbagh, Hussein I.,El-Azab, Adel S.,Hassan, Ghada S.,El-Messery, Shahenda M.,Abdel-Aziz, Alaa A.-M.,El-Taher, Kamal E.H.
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- Facile synthesis, spectral studies, DFT calculations and biological activities of novel NI (II), CU (II), and PD (II) complexes of thiadiazole analogs
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Objective: A facile synthesis of some novel Schiff base derivatives of 2-substituted-5-amino-thiadiazoles along with their Ni (II), Cu (II), and Pd (II) complexes were achieved by sonication and the conventional method. In addition to establish the structure by DFT studies and to explore antimicrobial and anticancer activities of these novel compounds. Methods: The precursor 2-substituted-5-amino-thiadiazoles (T1-T3), target ligands and their metal complexes were synthesized by ultrasonication and conventional means. The isolated products were thoroughly characterized by physical and spectroscopic techniques including1H-NMR,13C-NMR and IR spectroscopy. All characterized compounds were screened for antimicrobial activities using well diffusion method, and MTT assay was performed for cytotoxicity. Results: All novel compounds were synthesized by a green route i.e. ultra sonication and a noticeable improvement in yield with shorter reaction time than the conventional method were observed. The octahedral geometry was proposed for Ni (II)/Cu (II) complexes whereas square planar for Pd (II) complexes on the basis of the spectral techniques which were supported by DFT analysis by Gaussian03. On the analysis of antimicrobial activities, the compound T7 and T10 showed maximum antibacterial and antifungal activities respectively. However, compounds T25, T37, T31 found to be a potential cytotoxic compound with IC50 value 0.469, 0.865 and 1.131 μM respectively. Conclusion: Analysis of synthetic protocol, it could be concluded that ultra-sonication is the better method to synthesize these potential biological active moiety. On the whole Cu (II) and Ni (II) complexes showed promising activity towards all microorganisms while Pd (II) complex emerged an excellent moiety in carcinoma cell line.
- Bhatt, Priyanka,Deepthi,Ravi Shankar Kumar, Ch,Jha, Anjali
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p. 185 - 192
(2017/04/10)
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- Synthesis and evaluation of the trypanocidal activity of a series of 1,3,4-thiadiazoles derivatives of R-(+)-limonene benzaldehyde-thiosemicarbazones
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In this study, we synthesized a series of 1,3,4-thiadiazole derivatives of R-(+)-limonene benzaldehyde-thiosemicarbazones (2a–k). We also determined the cytotoxicity in LLCMK2 cells and the activity against epimastigote and trypomastigote forms
- Martins, Solange C.,Desoti, Vania C.,Lazarin-Bidóia, Danielle,Vandresen, Fábio,da Silva, Cleuza C.,Ueda-Nakamura, Tania,Silva, Sueli de O.,Nakamura, Celso V.
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p. 1193 - 1203
(2016/07/06)
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- Synthesis, biological evaluation and molecular modeling study of thiadiazolo[3,2-a][1,3]diazepine analogues of HIE-124 as a new class of short acting hypnotics
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A new series of 6,7-dihydro-[1,3,4]thiadiazolo[3,2-a][1,3]diazepine analogues were synthesized, and biological evaluated. Compound GS-62 (33) exhibited potent in?vivo short acting hypnotic activity with onset time, duration of sleep and therapeutic index of 6.4?±?0.2, 94.8?±?5.3?min, 6.62, respectively), in comparison to thiopental sodium (6). Compounds 33 did not show any sign of acute tolerance reported with the maintenance dose of 6. Meanwhile 33 potentiated the in?vivo hypnotic effect of 6 in an equimolar amounts (0.06?mmol) combination showing an onset and duration of 7.5?±?1.3, 62.5?±?5.9?min, respectively. This combination allowed the use of lower doses of both drugs to avoid the undesirable side effects. Docking studies revealed favorable interactions and binding to BDZ binding site of the GABAAreceptor especially with Arg87, Arg149, and Thr151 amino acid residues.
- El-Subbagh, Hussein I.,Hassan, Ghada S.,El-Taher, Kamal E.H.,El-Messery, Shahenda M.,El-Azab, Adel S.,Abdelaziz, Alaa A.-M.,Hefnawy, Mohamed M.
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p. 237 - 247
(2016/09/09)
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- Natural product-inspired rational design, synthesis and biological evaluation of 2,3-dihydropyrano[2,3-f]chromen-4(8H)-one based hybrids as potential mitochondrial apoptosis inducers
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Synthesis of novel pyranochromanone amide hybrids, by combining pyranochromanone pharmacophore and privileged scaffolds such as 2-amino-1,3,4-thiadiaole/2-aminothiazole/aminopyridine/aminonaphthalene and anti-cancer evaluation of a series led us to discover a series of new chemical entities (NCEs) showing broad spectrum of anti-cancer activity against three different human cancer cell lines (MCF-7, A549 and HeLa), at IC50values ranging from 14.3 to 97.8?μM. Among them, some compounds such as 15b, 15d, 20a and 20b displayed excellent activity against breast cancer cell line MCF-7. Detailed biological studies such as AO/EB dual staining, Hoechst 33342 staining, FACS analysis of mitochondrial membrane potential (Δψm) using JC-1 dye and DNA fragmentation confirmed the apoptosis induced by the hybrids. Gene expression studies by Real time RT-PCR has shown that these compounds are efficient regulator of anti-apoptotic gene Bcl-2. Western blot analysis also revealed that these compounds persuade apoptosis through intrinsic pathway by up-regulating the pro-apoptotic protein Bax and down-regulating the anti-apoptotic protein Bcl-2. Molecular docking studies reveal that compounds 15b and 20b binds efficiently with Bcl-2 promoter G-quadruplex.
- Sakthivel, Palaniappan,Ilangovan, Andivelu,Kaushik, Mahabir Prasad
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p. 302 - 318
(2016/07/11)
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- Molecular sieves promoted, ultrasound-mediated synthesis, biological evaluation and docking study of 3-(5-substituted-1,3,4-thiadiazol-2-ylimino)indolin-2-ones as a potential anticonvulsant agents
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In this work, the combined use of ultrasonic energy and molecular sieves was investigated for synthesis of 3-(5-substituted-1,3,4-thiadiazol-2-ylimino)indolin-2-one derivatives 5(a-j). The equimolar quantities of 5-substituted-1,3,4-thiadiazol-2-amine and
- Nikalje, Anna Pratima G.,Shaikh, Sameer I.,Kalam Khan, Firoz A.,Shaikh, Shoaib,Sangshetti, Jaiprakash N.
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p. 4058 - 4069
(2015/11/02)
-
- Synthesis and anti-inflammatory activity of some new thiadiazole linked pyrazole benzene sulphonamides as cyclooxygenase inhibitors
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A new series of thiadiazole linked pyrazole benzenesulfonamide derivatives were synthesized by the condensation of aldehydic pyrazole with aryl substituted thiadiazole amine followed by Schiff base reaction. The synthesized compounds (6a-o) were characterized by IR, NMR, and Mass spectral data, further evaluated their in-vivo anti-inflammatory, analgesic and invitro COX-II inhibition assay. The compounds 6b and 6m showed most significant in-vivo antiinflammatory with 72.33 &71.17% inhibition along analgesic activity having 67.89% and 71.37 % respectively. Their selectivity against COX-II enzyme with selectivity index 67.81 and 66.38 was established for 6b and 6m, which is compared with Celecoxib. During the gastric ulceration study, selected compounds couldn't observed any ulcerogenic effect on gastric mucosa. The in-silico pharmacokinetic profile and molecular docking study exposed very good binding affinity towards the Cyclooxygenase (COX-II) enzyme (PDB Id: 3PGH), therefore the compounds 6b and 6m are used as promising lead candidates for the support of drug development.
- Alam, Md. Jahangir,Alam, Ozair,Ali, Md. Rahmat,Naim, Mohd. Javed,Khan, Suroor Ahmad
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p. 1873 - 1885
(2016/02/27)
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- Photoredox catalysis of intramolecular cyclizations with a reusable silica-bound ruthenium complex
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Photoredox catalysis with the use of a stable, reusable silica-bound chromophore was applied to the intramolecular cyclization of a series of 2-benzylidenehydrazinecarbothioamides to give 5-phenyl-1,3,4-thiadiazol-2-amines. The catalyst was readily prepar
- Barbante, Gregory J.,Ashton, Trent D.,Doeven, Egan H.,Pfeffer, Frederick M.,Wilson, David J. D.,Henderson, Luke C.,Francis, Paul S.
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p. 1655 - 1658
(2015/06/08)
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- Synthesis of 2-amino-1,3,4-oxadiazoles and 2-Amino-1,3,4-thiadiazoles via sequential condensation and I2-mediated oxidative C-O/C-S bond formation
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2-Amino-substituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles were synthesized via condensation of semicarbazide/thiosemicarbazide and the corresponding aldehydes followed by I2-mediated oxidative C-O/C-S bond formation. This transition-metal-free sequential synthesis process is compatible with aromatic, aliphatic, and cinnamic aldehydes, providing facile access to a variety of diazole derivatives bearing a 2-amino substituent in an efficient and scalable fashion.
- Niu, Pengfei,Kang, Jinfeng,Tian, Xianhai,Song, Lina,Liu, Hongxu,Wu, Jie,Yu, Wenquan,Chang, Junbiao
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p. 1018 - 1024
(2015/01/30)
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- A Highly Efficient Diversification of 2-Amino/Amido-1,3,4-oxadiazole and 1,3,4-Thiadiazole Derivatives via Reagent-Based Cyclization of Thiosemicarbazide Intermediate on Solid-Phase
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A 2-amino/amido-1,3,4-oxadiazole and 1,3,4-thiadiazole library has been constructed on solid-phase organic synthesis. The key step on this solid-phase synthesis involves the preparation of polymer-bound 2-amino-1,3,4-oxadiazole and 1,3,4-thiadiazole core
- Yang, Seung-Ju,Choe, Ji-Hye,Abdildinova, Aizhan,Gong, Young-Dae
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p. 732 - 741
(2015/12/23)
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- Synthesis and antiproliferative assay of norcantharidin derivatives in cancer cells
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Diels-Alder reaction between furan and maleic anhydride resulted in 5,6-dehydro norcantharidin, then norcantharidin was obtained by reduction. The substituted-carboxylic acid was condensed with N-aminothiourea in presence of phosphorus oxychloride, yielding 2-amino-1,3,4-thiadiazole derivatives. Novel norcantharidin derivatives were synthesized with acylation, then intramolecular condensation using norcantharidin (or 5,6-dehydro norcantharidin) and 2-amino-1,3,4-thiadiazole derivatives. All the target compounds were confirmed by IR, 1HNMR, ESI-MS and were reported for the first time. Norcantharidin derivatives antiproliferative assay was tested by MTT method against A549 and PC-3 cell lines. The results showed that all the norcantharidin derivatives displayed moderate inhibitory activities.
- Tu, Guo Gang,Zhan, Jian Feng,Lv, Qiao Li,Wang, Jia Qi,Kuang, Bin Hai,Li, Shao Hua
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p. 376 - 381
(2014/05/20)
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- Improved antiproliferative activity of 1,3,4-thiadiazole-containing histone deacetylase (HDAC) inhibitors by introduction of the heteroaromatic surface recognition motif
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A series of 1,3,4-thiadiazole-containing hydroxamic acids, in accord with the common pharmacophore of histone deacetylase (HDAC) inhibitors (a Zn2+ binding moiety-a linker-a surface recognition motif), was identified as submicromolar HDAC inhibitors by our group. In this study, we continued our efforts to develop 1,3,4-thiadiazole bearing hydroxamate analogues by modifying the surface recognition motif. We found that 1,3,4-thiadiazoles having a heteroaromatic substituent showed better HDAC inhibitory activity in enzymatic assay and higher antiproliferative potency in cellular assay compared to SAHA.
- Guan, Peng,Wang, Lei,Hou, Xuben,Wan, Yichao,Xu, Wenfang,Tang, Weiping,Fang, Hao
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p. 5766 - 5775
(2015/02/02)
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- Synthesis, bioevaluation and docking study of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents
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Since the first histone deacetylase (HDAC) inhibitor (Zolinza, widely known as suberoylanilide hydroxamic acid; SAHA) was approved by the Food and Drug Administration for the treatment of T-cell lymphoma in 2006, the search for newer HDAC inhibitors has attracted a great deal of interest of medicinal chemists worldwide. As a continuity of our ongoing research in this area, we designed and synthesized a series of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as analogues of SAHA and evaluated their biological activities. A number of compounds in this series, for example, N1-hydroxy-N8-(5-(2-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (5b), N1-hydroxy-N8-(5-(3-chlorophenyl-1,3,4-thiadiazol-2-yl)octandiamide (5c) and N1-hydroxy-N8-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (5d), were found to possess potent anticancer cytotoxicity and HDAC inhibition effects. Compounds 5b-d were generally two- to five-fold more potent in terms of cytotoxicity compared to SAHA against five cancer cell lines tested. Docking studies revealed that these hydroxamic acid displayed higher affinities than SAHA toward HDAC8.
- Nam, Nguyen-Hai,Huong, Tran Lan,Dung, Do Thi Mai,Dung, Phan Thi Phuong,Oanh, Dao Thi Kim,Park, Sang Ho,Kim, Kyungrok,Han, Byung Woo,Yun, Jieun,Kang, Jong Soon,Kim, Youngsoo,Han, Sang-Bae
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p. 611 - 618
(2015/02/18)
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- Application of pocket modeling and k-nearest neighbor molecular field analysis (kNN-MFA) for designing of some anticoagulants: Potential factor IXa inhibitors
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The present communication deals with pharmacophore modeling, pocket modeling of the target site, and 3D QSAR analysis of 23 molecules of pyrazole-5-carboxamide from reported literature as factor IX inhibitors. The 3D QSAR analysis was carried out using k-
- Choudhari,Bhatia,Bhatia
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p. 976 - 985
(2013/04/10)
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- Design of benzothiazole-1,3,4-thiadiazole conjugates: Synthesis and anticonvulsant evaluation
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Various 2-[(6-substituted-1,3-benzothiazol-2-yl)amino]-N-[5-substituted- phenyl-1,3,4-thiadiazol-2-yl]acetamides were synthesized with a prospective exploration of "lead hopping", using pharmacophoric elements for in vivo anticonvulsant activity. This yielded three potent candidates (5i, 5t, and 5u) in the preliminary screening employing the maximal electroshock seizure (MES) and the subcutaneous pentylenetetrazole (scPTZ) test, showing minimal neurotoxicity. Their quantitative study indicated an increase of nearly 2-10 times for the MES test and 7- to 67-fold for the scPTZ test in the protective index, the keystone in drug discovery for anticonvulsant activity. Various 2-[(6-substituted-1,3-benzothiazol-2-yl)amino]-N-[5-substituted-phenyl-1,3, 4-thiadiazol-2-yl]acetamides were synthesized with a prospective exploration of "lead hopping", using pharmacophoric elements for in vivo anticonvulsant activity. Three potent candidates (5i, 5t, and 5u) with minimal neurotoxicity were identified in the MES and scPTZ tests.
- Siddiqui, Nadeem,Ahuja, Priya,Malik, Sachin,Arya, Satish K.
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p. 819 - 831
(2013/12/04)
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- Synthesis, characterization and preliminary in vitro antibacterial screening activity of metal complexes derivatives of 2-{[5-(4-nitrophenyl)-1,3, 4-thiadiazol-2-ylimino]methyl}phenol
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A total of five new metal complexes derivatives of 2-{[5-(4-nitrophenyl)-1, 3,4-thiadiazol-2-ylimino]methyl}phenol (HL) with the metal ions [Ni(II), Cu(II), Zn(II), Cd(II) and Sn(II)] have been successfully prepared in alcoholic medium. The complexes obtained are characterized quantitatively and qualitatively by using microelemental analysis, FTIR spectroscopy, UV-visible spectroscopy, mass spectroscopy, 1H and 13C NMR, magnetic susceptibility and conductivity measurements. From the spectral study, all the complexes obtained as monomeric structure and the metals centre moieties are four-coordinated with distorted tetrahedral geometry except Cu(II) complex which existed as a distorted square planar geometry. The preliminary in vitro antibacterial screening activity revealed that complexes 1-5 showed moderate activity against tested bacterial strains and slightly higher compared to the parent ligand.
- Win, Yip-Foo,Yousif, Emad,Ha,Majeed, Ahmed
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p. 4203 - 4206
(2013/07/19)
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- Mild and convenient one-pot synthesis of 2-amino-1,3,4-thiadiazoles using trimethylsilyl isothiocyanate (TMSNCS)
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A novel and efficient one-pot method has been developed for the synthesis of 2-amino-1,3,4-thiadiazoles using various carboxylic acid hydrazides with trimethylsilyl isothiocyanate (TMSNCS). In situ preparation of various thiosemicarbazides by the reaction
- Guda, Dinneswara Reddy,Cho, Hyeon Mo,Lee, Myong Euy
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p. 6813 - 6816
(2013/05/22)
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- New thiazolidinedione-5-acetic acid amide derivatives: Synthesis, characterization and investigation of antimicrobial and cytotoxic properties
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The present work describes the synthesis, antimicrobial and cytotoxic activity of 2,4-thiazolidinedione- 5-acetic acid amides 3a-n. The structures of the compounds were confirmed by IR, 1H, 13C NMR and elemental analysis. All compounds were tested for antimicrobial activity by twofold serial dilution technique. The preliminary results revealed that the compound 3d exhibits promising antibacterial and antifungal activity. The cytotoxic (MTT) activity of 2,4-thiazolidinedione-5-acetic acid amides were tested in four tumour cell lines. We found that compound 3j inhibited proliferation of HeLa, HT29, A549 and MCF-7 cell lines with IC50 values of 33, 35, 30 and 36 μM, respectively. Springer Science+Business Media, LLC 2011.
- Alegaon, Shankar G.,Alagawadi, Kallanagouda R.
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experimental part
p. 816 - 824
(2012/10/07)
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- An efficient synthesis of novel bis-1,3,4-thiadiazolyl-carbamate derivatives based on deoxycholic acid under microwave irradiation
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An easy and efficient method for the synthesis of novel deoxycholic acid bis-1,3,4-thiadiazol-carbamate derivatives under microwave irradiation has been developed. Twelve new methyl 3α,12α-bis-[(5-aryl-1,3,4-thiadiazol-2- yl) carbamoyloxy]-cholan-24-oates
- Zhao, Zhigang,Li, Lin,Liu, Min,Mei, Qinggang
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experimental part
p. 218 - 221
(2012/10/08)
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- Synthesis, docking and biological evaluation of some novel 5-bromo-2-(5-aryl-1,3,4-thiadiazol-2-yl)isoindoline-1,3-dione derivatives targeting ATP-binding site of topoisomerase II
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Human Topoisomerase IIα (htopoIIα) is an approved and validated target for designing anticancer agents. Among the various methods to block the functions of htopoIIα, targeting ATP site for its competitive inhibition has been relatively less investigated.
- Gupta, Ankur,Singh, Priya,Kamble, Bhagyashree,Kulkarni, Aditi,Chandrasekar, Moola Joghee Nanjan
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experimental part
p. 668 - 675
(2012/09/22)
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- Thiadiazole derivatives as potential anticonvulsant agents
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A series of thiadiazole derivatives were synthesized with differently substituted benzoic acids which were cyclized to give differently substituted thiazolidin-4-one. Elemental analysis, IR,1HNMR,13C NMR and mass spectral data confir
- Mullick, Pooja,Khan, Suroor A.,Verma, Surajpal,Alam, Ozair
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experimental part
p. 1011 - 1016
(2012/01/03)
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- Microwave-assisted synthesis of propesticides 1,3,4-thiadiazole aminophosphonates
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A novel and easy synthetic route to diethyl (5-substituted phenyl-1,3,4-thiadiazol-2-ylamino) (substituted phenyl) methylphosphonates has been achieved by the reaction of substituted benzylidene-5-(substituted phenyl)-1,3,4-thiadiazol-2-amines and diethyl phosphite under microwave irradiation. These 1,3,4-thiadiazole aminophosphonates were identified by infrared, 1H NMR, and elemental analyses. The target compounds were obtained in better yields (71-89%) and shorter time (10min) than with conventional heating.
- Wan, Rong,Wang, Peng,Han, Fen,Wang, Yao,Zhang, Jianqiang
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experimental part
p. 864 - 870
(2011/04/22)
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- Studies on nonlinear optical polyurethanes containing heterocyclic chromophores
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This paper presents the synthesis of highly stable nitro-substituted thiazole, benzothiazole and thiadiazole chromophores. With these, a series of second-order nonlinear optical (NLO) responsive polyurethanes were successfully synthesized from tolylene-2,
- Kariduraganavar,Tambe,Tasaganva,Kittur,Kulkarni,Inamdar
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experimental part
p. 158 - 165
(2011/04/14)
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- Synthesis and insecticidal activities of novel 1,3,4-thiadiazole 5-fluorouracil acetamides derivatives: An RNA interference insecticide
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A series of novel 1,3,4-thiadiazole 5-fluorouracil acetamides derivatives were designed and synthesized. Their structures were confirmed by infrared, 1H NMR spectroscopy, and elemental analysis. The insecticidal activities against Tetranychus cinnabarinus
- Wan, Rong,Zhang, Jian-Qiang,Han, Fen,Wang, Peng,Yu, Peng,He, Qiu
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experimental part
p. 280 - 292
(2012/02/03)
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- Synthesis and antimicrobial evaluation of 5-(p-substituted phenyl)-N-(3-(5-nitrofur-2-yl) allylidene)-1,3,4-thiadiazol-2-amine derivatives
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5-(p-Substituted phenyl)-N-(3-(5-nitrofur-2-yl)allylidene)-1,3,4- thiadiazol-2-amines 10-17 were prepared utilizing different p-substituted benzoic acid through two step reactions. Firstly, thiosemicarbzide was reacted with benzoic acid derivatives 1 in t
- Salih, Nadia,Salimon, Jumat,Yousif, Emad
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experimental part
p. 373 - 383
(2012/04/04)
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- Efficient synthesis of antifungal active 9-substituted-3-aryl-5H,13aH- quinolino[3,2-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines in ionic liquids
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The title compounds, 9-substituted-3-aryl-5H,13aH-quinolino[3,2-f][1,2,4] triazolo[4,3-b][1,2,4]triazepines 8, are synthesized from 5-aryl-3,4-diamino-1, 2,4-triazoles 5 and 2-chloro-3-formylquinolines 7 in ionic liquid as solvent under microwave heating as well as using oil-bath heating at 80 °C. The products are obtained in the good to moderate yields and in high purity. These compounds have been screened for antifungal activity. The screening data indicate that the compounds 8a, 8b, 8c and 8d show excellent activity against Aspergillus niger 1000 μg concentration and Pencillium notatum species at 500 μg as well as 1000 μg concentrations whereas, these compounds show good to moderate activity against Aspergillus flavus and Rhizopus species at both the concentrations. Moreover, ionic liquid is found to be recyclable for at least three consecutive runs what makes the process cost-effective and economic that lead to the area of Green Chemistry as recyclability is one of the most important feature of Green Chemistry.
- Gupta, Monika
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scheme or table
p. 4919 - 4923
(2011/09/16)
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- 2,5-Disubstituted-1,3,4-oxadiazoles/thiadiazole as surface recognition moiety: Design and synthesis of novel hydroxamic acid based histone deacetylase inhibitors
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The enzymatic inhibition of histone deacetylase activity has come out as a novel and effectual means for the treatment of cancer. Two novel series of 2-[5-(4-substitutedphenyl)-[1,3,4]-oxadiazol/thiadiazol-2-ylamino] -pyrimidine-5-carboxylic acid (tetrahydro-pyran-2-yloxy)-amides were designed and synthesized as novel hydroxamic acid based histone deacetylase inhibitors. The antiproliferative activities of the compounds were investigated in vitro using histone deacetylase inhibitory assay and MTT assay. The synthesized compounds were also tested for antitumor activity against Ehrlich ascites carcinoma cells in Swiss albino mice. The efforts were also made to establish structure-activity relationships among synthesized compounds. The results of the present studying indicates 2,5-disubstituted 1,3,4-oxadiazole/thiadiazole as promising surface recognition moiety for development of newer hydroxamic acid based histone deacetylase inhibitor.
- Rajak, Harish,Agarawal, Avantika,Parmar, Poonam,Thakur, Bhupendra Singh,Veerasamy, Ravichandran,Sharma, Prabodh Chander,Kharya, Murli Dhar
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supporting information; scheme or table
p. 5735 - 5738
(2011/10/09)
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- Synthesis of 2-N-salicylidene-5-(substituted)-1,3,4-thiadiazole as potential antimicrobial agents
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Several new 2,5-disubstituted derivatives of 1,3,4-thiadiazoles containing imine moiety were obtained from cyclization of thiosemicarbazide and corresponding p-substituted carboxylic acid in phosphorus oxychloride then the resulted products were reacted w
- Salimon, Jumat,Salih, Nadia,Ibraheem, Hanan,Yousif, Emad
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experimental part
p. 5289 - 5296
(2012/07/28)
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