Water‐Promoted Synthesis of Pyrazole‐Thiazole‐Derivatives as Potent Antioxidants And their Anti‐cancer Activity: ADMET and SAR Studies

Abstract

AbstractThe hybridization of two drugs crizotinib and febuxostat was used for designing the molecules which were synthesized using the Hantzsch thiazole synthetic method. The reaction was improved using a variety of solvents. Nonetheless, the product was developed in aqueous conditions with a high yield (87 %). The explored approach has various benefits, including catalyst‐free synthesis, purification without column chromatography, and a greener solvent. The antioxidant potential was assessed by DPPH (1,1‐diphenyl‐2‐picrilhydrazyl) radical scavenging activity for compounds 7 a, 7 e, 7 g, 7 i, 7 j. The percentage of DPPH radical scavenging activity ranged from 20.674 to 59.083. The best antioxidant capacity was shown by 7 a (IC50=8.46); In addition, bioavailability was predicted for compound 7 a by in‐silico calculations of ADMET (absorption, distribution, metabolism, excretion, and toxicity) and pharmacokinetic parameters. A total of 10 thiazole derivatives were synthesized and out of which 05 compounds were evaluated for their anti‐cancer activity against 60 distinct human tumor cell lines. Most of the synthesised compounds show moderate to good anti‐cancer activity.