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

Abstract

The 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.

Exploration of novel non-purine xanthine oxidase inhibitors based on oxadiazolones by an integrated simulation study

“…The amino or nitrogen-containing heterocycles of febuxostat analogues form stable hydrogen bonds with the surrounding residues in the binding pocket, with Glu802 playing a crucial role. 45,46 The backbone length of compound 45 was significantly shorter compared to that of compound 09 , resulting in a pronounced disruption of hydrogen bonding interactions between compound 45 and the key amino acids Asn768, Leu648, and Lys771 upon its entry into the binding pocket. Despite the presence of crucial hydrogen bonding interactions with amino acids Arg880 and Thr1010 (Arg880–N–H⋯OC, 2.0 Å) and (Thr1010–N–H⋯OC, 2.2 Å), the absence of interactions with specific essential amino acids still led to a noticeable decline in activity.…”