Structure-based Drug Design of New Cinnamic Acid Derivatives as Tyrosinase Inhibitors

Title:Structure-based Drug Design of New Cinnamic Acid Derivatives as Tyrosinase Inhibitors

Volume: 21 Issue: 8

Author(s): Fayezeh Yousefnejad, Mohammad Hossein Sayahi, Ali Moazzam, Fatemeh Gholami, Nader Tanideh, Cambyz Irajie, Helia Tayebi, Fatemeh Rasekh, Bagher Larijani, Maliheh Barazandeh Tehrani, Mohammad Mahdavi*Aida Iraji*

Affiliation:

• Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

• Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
• Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran

Keywords: Tyrosinase inhibition, cinnamic acid, synthesis, molecular docking, kinetic study, melanin.

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 acidbased 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 para-chloro 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.

Cite this article as:

Yousefnejad Fayezeh, Sayahi Hossein Mohammad, Moazzam Ali, Gholami Fatemeh, Tanideh Nader, Irajie Cambyz, Tayebi Helia, Rasekh Fatemeh, Larijani Bagher, Tehrani Barazandeh Maliheh, Mahdavi Mohammad*, Iraji Aida*, Structure-based Drug Design of New Cinnamic Acid Derivatives as Tyrosinase Inhibitors, Letters in Organic Chemistry 2024; 21 (8) . https://dx.doi.org/10.2174/0115701786263337231227113513