2-Aminothiazole-Oxadiazole Bearing N-Arylated Butanamides: Convergent Synthesis, Tyrosinase Inhibition, Kinetics, Structure-Activity Relationship, and Binding Conformations

• Published in: Chemistry and Biodiversity
• Main Author: Raza H.; Rehman Sadiq Butt A.; Athar Abbasi M.; Aziz-ur-Rehman; Zahra Siddiqui S.; Hassan M.; Adnan Ali Shah S.; Ja Kim S.
• Format: Article
• Language: English
• Published: John Wiley and Sons Inc 2023
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85146447713&doi=10.1002%2fcbdv.202201019&partnerID=40&md5=98c0f4a01d5482f9a3e94ed5bee9d376

A multi-step synthesis of novel bi-heterocyclic N-arylated butanamides was consummated through a convergent strategy and the structures of these medicinal scaffolds, 7a–h, were corroborated using spectral techniques. The in vitro analysis of these hybrid molecules revealed their potent tyrosinase inhibition as compared to the standard used. The kinetics mechanism was investigated through Lineweaver-Burk plots which exposed that, 7f, inhibited tyrosinase enzyme non-competitively by forming the enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.025 μM. Their binding conformations were ascertained by in silico computational studies whereby these molecules disclosed good binding energy values (kcal/mol). So, it was anticipated from the current research that these bi-heterocyclic butanamides might be probed as imperative therapeutic agents for melanogenesis. © 2023 Wiley-VHCA AG, Zurich, Switzerland.