Elucidating bis-pyrimidines as new and efficient mushroom tyrosinase inhibitors: synthesis, SAR, kinetics and computational studies
Manazza Afzal, Rabia Mehmood, Ehsan Ullah Mughal, Nafeesa Naeem, Zaman Ashraf, Yasir Nazir, Fatma Mohsen Shalaby, Amal El-Sayed Abd El Hady, Amina Sadiq
Abstract
values ranging from 12.36 ± 1.24 to 86.67 ± 3.08 μM. To further elucidate the binding interactions, molecular docking simulations were performed, identifying key residues in the active site responsible for binding affinity. Furthermore, molecular dynamics (MD) simulations were conducted to assess the dynamic behavior, stability, and binding affinity of the most potent inhibitor, compound 6P. Quantitative Structure-Activity Relationship (QSAR) models were developed to correlate the structural features of the bis-pyrimidines with their inhibitory activity, providing insights into the structure-activity relationships (SAR) that govern their potency. The experimental and theoretical findings demonstrated excellent agreement. These findings pave the way for the development of novel bis-pyrimidine-based therapeutic agents for treating hyperpigmentation and related conditions.