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Structure-Based Drug Design of New Cinnamic Acid Derivatives As Tyrosinase Inhibitors Publisher



F Yousefnejad FAEZE ; Mh Sayahi Mohammad HOSEIN ; A Moazzam ALI ; F Gholami FATEMEH ; N Tanideh NADER ; C Irajie CAMBYZ ; H Tayebi HELIA ; F Rasekh FATEMEH ; Ba Larijani Bagher A ; Mh Barazandeh Tehrani Maliheh HOSSEINPOUR
Authors

Source: Letters in Organic Chemistry Published:2024


Abstract

Tyrosinase is a critical enzyme responsible for pigmentation disorders, and tyrosinase inhibition is an established strategy to treat hyperpigmentation. In the current study, cinnamic acid-based derivatives were designed and synthesized. All synthesized compounds were confirmed using IR, 1HNMR, 13CNMR, and CNH analysis. The inhibitory potencies of all derivatives against tyrosinase were determined, and it was shown that 5m bearing parachloro moiety exhibits an IC50 value of 77.62 μmol/L. Analysis of enzyme kinetic studies revealed that 5m is an uncompetitive inhibitor. In silico studies against tyrosinase predicted possible binding mode in the pocket such that 5m formed critical interactions with both Cu co-factors within the binding site. This study presents the potential of aryl-substituted cinnamic acids that can benefit various cosmetic formulations as depigmentation agents. © 2024 Elsevier B.V., All rights reserved.
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