330978-60-4Relevant articles and documents
Thiazole-5-carboxylic acid derivatives as potent xanthine oxidase inhibitors: design, synthesis, in vitro evaluation, and molecular modeling studies
Kaur, Gurinder,Singh, Jatinder V.,Gupta, Manish K.,Bhagat, Kavita,Gulati, Harmandeep K.,Singh, Atamjit,Bedi, Preet Mohinder S.,Singh, Harbinder,Sharma, Sahil
, p. 83 - 93 (2020)
A series of 22 compounds of thiazole-5-carboxylic acid derivatives was rationally designed and synthesized. All the compounds were characterized by using 1H and 13C NMR and tested against xanthine oxidase enzyme by spectrophotometric assay. Majority of the compounds were found active against the enzyme amongst which GK-20 with an IC50 value of 0.45 μM was found to be most potent. Structure-activity relationship obtained from the biological results revealed that the di-substituted compounds as Ring B were more potent than that of mono-substituted derivatives. Para-substitution on Ring B is crucial for the xanthine oxidase inhibitory potential. Enzyme kinetic studies further revealed their mixed type inhibition behavior. Moreover, the binding pattern of the most potent compound GK-20 within the febuxostat binding site of the enzyme was further analyzed by using docking studies which revealed that it sufficiently block the catalytic active site, which prevents the substrate to bind.
2-Benzamido-4-methylthiazole-5-carboxylic Acid Derivatives as Potential Xanthine Oxidase Inhibitors and Free Radical Scavengers
Ali, Md. Rahmat,Kumar, Suresh,Afzal, Obaid,Shalmali, Nishtha,Ali, Wazid,Sharma, Manju,Bawa, Sandhya
, (2017/02/15)
The new chemical entities febuxostat and topiroxostat have been approved by the US Food and Drug Administration, opening new avenues for exploiting different heterocycles other than purines as xanthine oxidase (XO) inhibitors. A different series of substituted 2-benzamido-4-methylthiazole-5-carboxylic acid derivatives (5a–r) was synthesized and characterized by the collective use of IR, 1H and 13C NMR, and mass spectroscopy, for the treatment of gout and hyperuricemia. In vitro studies of the synthesized derivatives revealed that the presence of a fluoro group at the para position in 5b (IC50 = 0.57 μm) and a chloro group in 5c (IC50 = 0.91 μm) signifies excellent XO inhibitory activity among the series, along with their DPPH free radial scavenging activity. In vivo serum uric acid inhibition studies established that 5b and 5c displayed 62 and 53% uric acid inhibition, respectively. Studies on enzyme kinetics indicated that 5b acts as a mixed type inhibitor. In silico prediction by various softwares also helped in the recognition of potent XO inhibitors.
Microwave induced synthesis of fluorobenzamides containing thiazole and thiazolidine as promising antimicrobial analogs
Desai,Rajpara,Joshi
, p. 102 - 111 (2013/04/10)
New 5-arylidene derivatives, which bear a fluorine atom in the 4th position of the benzoyl group as starting compound, have been synthesized by the condensation of 4-fluoro-N-(4-methyl-5-(2-(4-oxo-3-phenylthiazolidin-2-ylidene) hydrazinecarbonyl)thiazol-2-yl)benzamide and Knoevenagel condensation with aromatic aldehydes to form N-(5-(2-(5-(arylidene)-4-oxo-3-phenylthiazolidin-2- ylidene)hydrazinecarbonyl)-4-methylthiazol-2-yl)-4-fluorobenzamides (6a-o) through conventional and microwave methods. The structures of synthesized compounds were established by spectroscopic as well as spectrometric techniques (IR, 1H NMR, 13C NMR, 19F NMR spectroscopy and mass spectrometry). Antimicrobial screening of 5-arylidene derivatives 6a-o was done against Gram-positive bacteria (Staphylococcus aureus and Streptococcus pyogenes), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and fungi (Candida albicans, Aspergillus niger, and Aspergillus clavatus) using serial broth dilution method. Compounds 6g and 6j were found to be most active at MIC 12.5 μg/mL against selected bacterial strains and compound 6e was found to be most active at MIC 25 μg/mL against selected fungal strains. It has been further observed that the presence of fluorine atom at the 4th position of the benzoyl group in the final compounds is essential for enhancing the antimicrobial activity.
