- Synthesis and cytotoxicity evaluation of [(2,4-dichlorophenoxy)methyl]-5-aryl-1,3,4-oxadiazole/4H-1,2,4-triazole analogues
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We report herein the synthesis, characterization, and cytotoxicity evaluations of some newer oxadiazole and triazole analogues (5a-j). The cytotoxicity of all the title compounds were evaluated as per the National Cancer Institute protocol in a one-dose assay (10M) on nine different panels of 59 cancer cell lines. 2-f5-[(2,4-Dichlorophenoxy)methyl]-1,3,4-oxadiazol-2-ylgphenol (5e) showed the maximum cytotoxicity among the series of ten compounds. The cytotoxicity of 5e was comparable to that of the standard anticancer drug, 5-fluorouracil, and better than that of imatinib. The structure activity relationship was also discussed.
- Ahsan, Mohamed Jawed
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- (2,4-Dichlorophenoxy)acetohydrazide
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The title compound, C8H8Cl2N2O2, is an intermediate compound in the synthesis of one of the important 1,2,4-triazoles that possess diverse pharmacological activities.
- Lokanath,Sridhar,Shashidhara Prasad,Nagaraja,Mohan Rao
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- Design, synthesis and molecular modelling of phenoxyacetohydrazide derivatives as Staphylococcus aureus MurD inhibitors
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In the present work we synthesized a new series of phenoxyacetohydrazide functional compounds 4a-k and characterized by spectral data. Synthesized compounds were screened in vitro for their antibacterial activity. Compounds 4a, 4j and 4k exhibited inhibitory activity against S. aureus NCIM 5022 with MIC value of 64?μg/ml These compounds also exhibited activity against methicillin resistant S. aureus ATCC 43300 with MIC of 128?μg/ml. Among all the tested compounds 4c and 4j showed highest activity, respectively against B. subtilis NCIM 2545 and K. pneumoniae NCIM 2706. Only one compound i.e. 4d showed activity against another Gram-negative bacteria P. aeruginosa NCIM 2036 with MIC value of 64?μg/ml. Among three tested compounds, 4k exhibited highest inhibitory activity against S. aureus MurD enzyme with IC50 value of 35.80?μM. Further binding interactions of 4a-k with the modelled S. aureus MurD catalytic pocket residues is investigated with the extra-precision molecular docking and binding free energy calculation by MM-GBSA approach. The van der Waals energy term was observed to be the driving force for binding. Further, 50?ns molecular dynamics simulations were performed to validate the stabilities of 4j- and 4k-modelled S. aureus MurD. Graphic abstract: [Figure not available: see fulltext.]
- Jupudi, Srikanth,Azam, Mohammed Afzal,Wadhwani, Ashish
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p. 1221 - 1235
(2020/10/09)
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- Design, synthesis, in vitro and in silico studies of some novel triazoles as anticancer agents for breast cancer
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Against the increasing incidence of breast cancer in postmenopausal women in recent years, a few clinically approved inhibitors and their side-effect profiles indicate the need for the development of new aromatase inhibitors. In this study, carried out to develop a new aromatase inhibitor, the triazole ring system was preferred because of its known activity in the field. The triazole ring, which is in the structure of the most commonly used aromatase inhibitors such as anastrazole and letrazole, was synthesized from the thiourea residue. Inhibitor structures were elucidated using the 1H-NMR, 13C-NMR, 2D-NMR, and HRMS spectroscopic methods. A cytotoxicity (MTT) test was performed to determine the anticancer activity of the compounds on breast (MCF7) carcinoma cell type. In addition, to determine selectivity of their action, the final compounds were screened against a healthy NIH3T3 cell line (mouse embryonic fibroblast cells). In terms of the MTT assay, it was observed that the calculated IC50 values of compound 5e for the NIH3T3 cell line were found to be higher than for the MCF7 cell lines. Considering the viability results, it was found that the selected compound 5e showed a favorable safety profile and that it has anticancer activities. It was determined by in vitro studies that compound 5e showed inhibition potential on the aromatase enzyme with an IC50 = 0.028 μM value. The docking study of compound 5e revealed that there is a strong interaction between the active sites of the human aromatase enzyme and the analyzed compound.
- ?zkay, Yusuf,Ilg?n, Sinem,Kaplanc?kl?, Zafer As?m,Levent, Serkan,Osmaniye, Derya,Sa?l?k, Begüm Nurpelin
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- Expedient discovery for novel antifungal leads: 1,3,4-Oxadiazole derivatives bearing a quinazolin-4(3H)-one fragment
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Developing novel fungicide candidates are intensively promoted by the rapid emergences of resistant fungi that outbreak on agricultural production. Aiming to discovery novel antifungal leads, a series of 1,3,4-oxadiazole derivatives bearing a quinazolin-4(3H)-one fragment were constructed for evaluating their inhibition effects against phytopathogenic fungi in vitro and in vivo. Systematically structural optimizations generated the bioactive molecule I32 that was identified as a promising inhibitor against Rhizoctonia solani with the in vivo preventative effect of 58.63% at 200 μg/mL. The observations that were captured by scanning electron microscopy and transmission electron microscopy demonstrated that the bioactive molecule I32 could induce the sprawling growth of hyphae, the local shrinkage and rupture on hyphal surfaces, the extreme swelling of vacuoles, the striking distortions on cell walls, and the reduction of mitochondria numbers. The above results provided an indispensable complement for the discovery of antifungal lead bearing a quinazolin-4(3H)-one and 1,3,4-oxadiazole fragment.
- Chai, Jianqi,Chen, Min,Jin, Fei,Kong, Xiangyi,Wang, Xiaobin,Xue, Wei,Yang, Chunlong
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- Synthesis and Insecticidal Evaluation of Novel N-pyridylpyrazole Derivatives Containing Diacylhydrazine/1,3,4-Oxadiazole Moieties
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Two series of novel N-pyridylpyrazole derivatives containing diacylhydrazine/1,3,4-oxadiazole moieties were designed and synthesized based on the structure of chlorantraniliprole and characterized via 1H-NMR, 13C-NMR, IR, MS, and elemental analysis. The preliminary bioassay indicated that some of the title compounds I and II exhibited larvicidal activities against Mythimna separata with 90–100% death rates at 500?mg/L. The further test showed that these compounds had weak insecticidal activity against Mythimna separata and Plutella xylostella at 200?mg/L and might be not suitable as insecticide lead compound for further optimization.
- Wang, Wei,Zheng, Xiao-Rui,Huang, Xiao-Ying,Mao, Ming-Zhen,Liu, Kang-Yun,Xue, Chao,Wang, Lie-Ping,Ning, Bin-Ke
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p. 1330 - 1336
(2019/01/30)
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- Synthesis and biological evaluation of some new furoxan derivatives as anti-inflammatory agents
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A new series of furoxan derivatives (3a-k) have been synthesized and characterized by their IR, 1H NMR and mass spectral data. All the compounds have been screened for their anti-inflammatory activity. The compounds 3a, 3b, 3f, 3g, and 3i which show significant anti-inflammatory activity have been further studied for their ulcerogenic activities and nitric oxide releasing properties. Furoxan derivative 3-memyl-4-[{2-(2-phenylacetyl)hydrazono}memyl]-furoxan 3f showed greater anti-inflammatory activity comparable to standard drug ibuprofen. The compound also showed reduced, ulcerogenicity and high nitric oxide releasing properties.
- Amir, Mohd,Verma, Jeevan S.,Tariq, Sana,Somakala,Ehtaishamul Haq
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p. 955 - 959
(2019/05/21)
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- Synthesis and antibacterial evaluation of new sulfone derivatives containing 2-aroxymethyl-1,3,4-oxadiazole/thiadiazole moiety
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Sulfones are one of the most important classes of agricultural fungicides. To discover new lead compounds with high antibacterial activity, a series of new sulfone derivatives were designed and synthesized by introducing the aroxymethyl moiety into the scaffold of 1,3,4-oxadiazole/thiadiazole sulfones. Antibacterial activities against three phytopathogens (Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, Xanthomonas axonopodis pv. citri.) were assayed in vitro. As compared to the control of commercial fungicides and some reported sulfone fungicides, seven compounds 5I-1-5I-7 exerted remarkably higher activities with EC50 values ranging from 0.45-1.86 μg/mL against X. oryzae and 1.97-20.15 μg/mL against R. solanacearum. Exhilaratingly, 5I-1, 5I-2 and 5I-4 displayed significant in vivo activity against X. oryzae with protective effect of 90.4%, 77.7%, and 81.1% at 200 μg/mL, respectively, much higher than that exhibited by Bismerthiazol (25.6%) and Thiadiazole-copper (32.0%). And the differential phytotoxicity of active derivatives was preliminarily checked. The results demonstrated that derivative of 2-aroxymethyl-1,3,4-oxadiazole/thiadiazole sulfone can serve as potential alternative bactericides for the management of plant bacterial diseases.
- Su, Shihu,Zhou, Xia,Liao, Guoping,Qi, Puying,Jin, Linhong
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- Synthesis and Herbicidal Activity of Some Novel Pyrazole Derivatives
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Some novel pyrazole derivatives were designed and synthesized through multi-step reactions from substituted phenol as starting material. Their structures were confirmed by 1H NMR, FTIR, MS and elemental analysis. All these compounds were evaluated their herbicidal activity. The preliminary bioassay results indicated that some of title compounds displayed moderate herbicidal activity at 200 μg/mL. Among them, compounds 4-chloro-N'-(2-(2,5-dimethyl-phenoxy) acetyl)-3-ethyl-1-methyl-1H-pyrazole-5-carbohydrazide, 4-chloro-N'-(2-(2,4-dichlorophenoxy)acetyl)- 3-ethyl-1-methyl-1H-pyrazole-5-carbohydrazide, 4-chloro-3-ethyl-1-methyl-N'-(2-(m-tolyloxy) acetyl)-1H-pyrazole-5-carbohydrazide and 4-chloro-3-ethyl-1-methyl-N'-(2-(3-nitrophenoxy)acetyl)- 1H-pyrazole-5-car-bohydrazide possessed 95%, 100%, 95% and 95% inhibition against Brassica campestris respectively. In the further bioassay, the compound 6l exhibited excellent herbicidal activity either monocotyledon or dicotyledon plant at 150 g/ha.
- He, Hai-Qin,Liu, Xing-Hai,Weng, Jian-Quan,Tan, Cheng-Xia
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p. 195 - 200
(2017/07/22)
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- Synthesis of acylhydrazines and, symmetrical and asymmetrical diacylhydrazines from carboxylic acid via the Vilsmeier reagent mediated process
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(Chloromethylene)dimethylammonium chloride (Vilsmeier reagent) has been used as an efficient and convenient reagent for the one-pot synthesis of acylhydrazines and symmetrical and asymmetrical diacylhydrazines from carboxylic acids. This reaction proceeded smoothly under mild conditions and it is quite practical, since the starting carboxylic acids can be easily handled and stored. Cleanliness, simplicity of the method and good to excellent yield of products are other advantages of this method.
- Zarei, Maaroof,Nakhli, Maliheh Eslami
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p. 1909 - 1918
(2017/02/15)
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- One-pot synthesis of 1,3,4-thiadiazoles using Vilsmeier reagent as a versatile cyclodehydration agent
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A simple and efficient synthetic method for the one-pot synthesis of 1,3,4-thiadiazoles utilizing Vilsmeier reagent was developed. In this method carboxylic acids and hydrazine were converted to 1,3,4-thiadiazoles in the presence of Vilsmeier reagent and Lawesson's reagent. The influence of the thionation reagent, solvent, temperature and time, in this reaction was discussed. The developed methodology for 1,3,4-thiadiazole synthesis has the advantage of simplicity, ambient reaction conditions, easy purification and good to excellent yield of products.
- Zarei, Maaroof
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p. 1867 - 1872
(2017/03/11)
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- Novel 2,4-dichlorophenoxy acetic acid substituted thiazolidin-4-ones as anti-inflammatory agents: Design, synthesis and biological screening
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A library of fourteen 2-imino-4-thiazolidinone derivatives (1a-1n) has been synthesized and evaluated for in vivo anti-inflammatory activity and effect on ex-vivo COX-2 and TNF–α expression. Compounds 1k (5-(2,4-dichloro-phenooxy)-acetic acid (3-benzyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) and 1m (5-(2,4-dichloro-phenooxy)-acetic acid (3-cyclohexyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) exhibited in vivo inhibition of 81.14% and 78.80% respectively after 5 h in comparison to indomethacin which showed 76.36% inhibition of inflammation without causing any damage to the stomach. Compound 1k showed a reduction of 68.32% in the level of COX-2 as compared to the indomethacin which exhibited 66.23% inhibition of COX-2. The selectivity index of compound 1k was found to be 29.00 in comparison to indomethacin showing selectivity index of 0.476. Compounds 1k and 1m were also found to significantly suppress TNF-α concentration to 70.10% and 68.43% in comparison to indomethacin which exhibited 66.45% suppression.
- Ali, Yakub,Alam, Mohammad Sarwar,Hamid, Hinna,Husain, Asif,Dhulap, Abhijeet,Bano, Sameena,Kharbanda, Chetna
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p. 1017 - 1025
(2017/09/30)
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- Anthelmintic evaluation of some novel synthesized 1,2,4-triazole moiety clubbed with benzimidazole ring
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A series of N-[3-{(1H-benzo[d]imidazol-2-ylthio) methyl}-5-mercapto-4H-1,2, 4-triazol-4-yl]-2-substituted phenoxy acetamide 6(a-g) were synthesized by the mixture of the compound of potassium 2-(2-(1H-benzo[d]imidazol-2-ylthio) acetyl) hydrazinecarbodithioate (4) and arytoxy acid hydrazide (5) in presence of hydrochloric acid. The predicted structures of the synthesized compounds were confirmed by different spectral analysis studies. The title compounds 6(a-g) were screened for anthelmintic activity against Pheretima posthumous. The entire compounds were exhibited good anthelmintic activity when compared with standard drugs such as Albendazole and Piperazine.
- Kumar, P. Sudhir,Sahoo
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p. 211 - 217
(2014/06/23)
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- Aggrecanase-2 inhibitors based on the acylthiosemicarbazide zinc-binding group
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Osteoarthritis is a disabling disease characterized by the articular cartilage breakdown. Aggrecanases are potential therapeutic targets for the treatment of this pathology. At the starting point of this project, an acylthiosemicarbazide was discovered to inhibit aggrecanase-2. The acylthiosemicarbazide Zn binding group is also a convenient linker for library synthesis. A focused library of 920 analogs was thus prepared and screened to establish structure-activity relationships. The modification of the acylthiosemicarbazide was also explored. This strategy combining library design and discrete compounds synthesis yielded inhibitor 35, that is highly selective for aggrecanases over a panel of metalloproteases and inhibits the degradation of native fully glycosylated aggrecan. A docking study generated binding conformations explaining the structure-activity relationships.
- Maingot, Lucie,Elbakali, Jamal,Dumont, Julie,Bosc, Damien,Cousaert, Nicolas,Urban, Agathe,Deglane, Gaelle,Villoutreix, Bruno,Nagase, Hideaki,Sperandio, Olivier,Leroux, Florence,Deprez, Benoit,Deprez-Poulain, Rebecca
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p. 244 - 261
(2013/10/01)
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- Design, synthesis, biological activities and 3D-QSAR of new N,N′-diacylhydrazines containing 2,4-dichlorophenoxy moieties
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A series of new N,N′-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by 1H-NMR, MS and elemental analysis. The herbicidal activities and plant growth regulating activity of these N,N′-diacylhydrazines were evaluated. The herbicidal activity results showed that most of these N,N′-diacyl-hydrazines showed excellent in vivo activities against Echinochloa crus-galli, Digitaria sanguinalis, Brassica napus, Amaranthus retroflerus. Most of them exhibited higher herbicidal activities against dicotyledonous weeds than monocotyledonous weeds. To further investigate the structure-activity relationship, comparative molecular field analysis (CoMFA) was performed on the basis of herbicidal activity data. Both the steric and electronic field distributions of CoMFA are in good agreement in this work.
- Sun, Guo-Xiang,Sun, Zhao-Hui,Yang, Ming-Yan,Liu, Xing-Hai,Ma, Yi,Wei, Yun-Yang
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p. 14876 - 14891
(2014/01/17)
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- Biolabeling with 2,4-dichlorophenoxyacetic acid derivatives: The 2,4-D tag
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Many bioanalytic and diagnostic procedures rely on labels with which the molecule of interest can be tracked in or discriminated from accompanying like substances. Herein, we describe a new labeling and detection system based on derivatives of 2,4-dichlorophenoxyacetic acid (2,4-D) and anti-2,4-D antibodies. The 2,4-D system is highly sensitive witha KDof7×10 -11Mforthehapten-antibody pair, can be used on a large variety of biomolecules such as proteins, peptides, carbohydrates, and nucleic acids, is not hampered by endogenous backgrounds because 2,4-D is a xenobiotic, and is robust because 2,4-D is a very stable compound that withstands the conditions of most reactions usually performed on biomolecules. With this unique blend of properties, the 2,4-D system compares favorably with its rivals digoxigenin (DIG)/anti-DIG and biotin/(strept)avidin and provides an interesting and powerful tool in biomolecular labeling.
- Bade, Steffen,Roeckendorf, Niels,Franek, Milan,Gorris, Hans H.,Lindner, Buko,Olivier, Verena,Schaper, Klaus-Juergen,Frey, Andreas
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p. 9695 - 9702
(2010/04/24)
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- Synthesis and antimicrobial studies on novel chloro-fluorine containing hydroxy pyrazolines
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A series of chloro-fluorine containing chalcones (3) were prepared by Claisen-Schmidt condensation. Chalcone dibromides (4) were obtained by the bromination of chalcones at room temperature. Treatment of chalcone dibromides (4) with aryloxy acid hydrazide
- Karthikeyan, Mari Sithambaram,Holla, Bantwal Shivarama,Kumari, Nalilu Suchetha
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- An expedient method for the synthesis of acylhydrazones under microwave irradiation in solvent-free medium
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A simple, efficient and eco-friendly method for the synthesis of acylhydrazones from acylhydrazides and aldehydes under microwave (MW) irradiation was reported, no solvent and catalyst was used. The method is combined with a combinatorial approach and fou
- Li, Jian-Ping,Zheng, Peng-Zhi,Zhu, Jun-Ge,Liu, Rui-Jie,Qu, Gui-Rong
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- A rapid and high-yield synthesis of aryloxyacetyl hydrazides under microwave irradiation and with phase transfer catalysis
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A series of aryloxyacetyl hydrazides 4a-l were synthesised under microwave irradiation and phase transfer catalysis conditions. By the optimisation of the reaction conditions, a rapid, high-yield and efficient method for the preparation of aryloxyacety hydrazide was given.
- Wei, Tai-Bao,Liu, Hong,Li, Man-Lin,Zhang, You-Ming
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p. 432 - 433
(2007/10/03)
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- Synthesis and anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities of 3,5-dimethyl pyrazoles, 3-methyl pyrazol-5-ones and 3,5-disubstituted pyrazolines
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3,5-Dimethyl pyrazole 3a-d and 3-methyl pyrazol-5-one 4a-d derivatives of diclofenac, ibuprofen, flurbiprofen and 2,4-dichlorophenoxy acetic acid have been synthesized. In addition, substituted pyrazoline derivatives of ibuprofen 6a-e have also been prepared by treating different chalcones 5a-e with ibuprofen hydrazide. Some of the newly synthesized compounds are screened for anti-inflammatory activity and few compounds showing 80% activity are selected for analgesic, ulcerogenic and lipid peroxidation activities.
- Amir, Mohd,Kumar, Shikha
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p. 2532 - 2537
(2007/10/03)
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- Synthesis and quantitative structure - Activity relationships of new 2,5-disubstituted-1,3,4-oxadiazoles
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Fourteen new 2,5-disubstituted-1,3,4-oxadiazoles, namely (i) six 2-[2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropyl]-5-substituted-1,3,4-oxadia zoles and (ii) eight 2-substituted-phenoxymethyl-5-substituted-aryl-1,3,4-oxadiazoles, were synthesized and evaluated for their insect growth regulatory activity against second-instar larvae of armyworm (Pseudaletia separata Walker). Two of these compounds (7 and 8) showed good insecticidal activities, with LC50 values of 14.33 and 15.85 μg/mL, respectively. Steric parameters (e.g., the molecular length d and the ratio of the nonpolar surface area and polar surface area V1/V2) and semiempirical quantum parameters (e.g., the molecular total energy Et and the lowest unoccupied molecular orbital energy ELUMO and so on) of these compounds, as well as those of six other 2,5-disubstituted-1,3,4-oxadiazoles reported, were acquired by the molecular modeling method and the PM3-SCF-MO method, respectively. With the help of the synthons' activity contribution method based on the Free-Wilson approach in its Fujita-Ban variant, quantitative structure-activity relationships were studied by regressing half-lethal concentrations against the above parameters.
- Shi, Wei,Qian, Xuhong,Zhang, Rong,Song, Gonghua
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p. 124 - 130
(2007/10/03)
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- Synthesis, Characterization, Spectral and Antifungal Properties of Some 5-Substituted-1,3,4-oxadiazole-2-thiones and Their Mannich Bases
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A series of 5-substituted aryloxymethyl-1,3,4-oxadiazole-2-thione (3a-e) and their Mannich bases 4-8 are synthesized and subjected to fungitoxic screening.The structures of these compounds are established on the basis of elemental analysis 1H-n.m.r. and mass spectral data.The mass spectral fragmentation pathways of these compounds are discussed.
- Holla, B. Shivarama,Kalluraya, Balakrishna,Nath, S. C.
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p. 549 - 557
(2007/10/02)
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