Synthesis and structure-activity relationship of elastase inhibiting novel ethylated thiazole-triazole acetamide hybrids: Mechanistic insights through kinetics and computational contemplations

• Published in: Bioorganic Chemistry
• Main Author: Butt A.R.S.; Abbasi M.A.; Aziz-ur-Rehman; Siddiqui S.Z.; Hassan M.; Raza H.; Shah S.A.A.; Seo S.-Y.
• Format: Review
• Language: English
• Published: Academic Press Inc. 2019
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060856533&doi=10.1016%2fj.bioorg.2019.01.040&partnerID=40&md5=b1b89e8217b618d2cfdce588785cad50

Keeping in mind the pharmacological importance of 2-aminothiazole and 1,2,4-triazole heterocyclic moieties, a series of novel ethylated bi-heterocyclic acetamide hybrids, 9a–p, was synthesized in a multi-step protocol. The structures of newly synthesized compounds were characterized by 1 H NMR, 13 C NMR, IR and EI-MS spectral studies. The inhibitory effects of these bi-heterocyclic acetamides (9a–n) were evaluated against elastase and all these molecules were identified as potent inhibitors relative to the standard used. The Kinetics mechanism was analyzed by Lineweaver-Burk plots which revealed that, 9h, inhibited elastase competitively by forming an enzyme-inhibitor complex. The inhibition constants K i calculated from Dixon plots for this compound was 0.9 µM. The computational study was articulate with the experimental results and these ligands unveiled good binding energy values (kcal/mol). So, these molecules can be considered as promising medicinal scaffolds for the treatment of skin melanoma, wrinkle formation, uneven pigmentation, and solar elastosis. © 2019 Elsevier Inc.