Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase Inhibitors

Abstract

In the current study, a series of dihydropyrimidinone derivatives were rationally designed as β-glucuronidase inhibitors. These designed compounds were successfully synthesized and characterized through various spectroscopic techniques such as IR, 1H-NMR, 13C-NMR, and EI-MS. A structure-activity relationship (SAR) of synthesized derivatives to inhibit β-glucuronidase was also established. In vitro biological evaluations revealed that 4i as the most potent compound in this series has an IC50 value of 31.52 ± 2.54 μM compared to the standard D-saccharic acid 1,4-lactone (IC50 = 41.32 ± 1.82 µM). Also, molecular docking and dynamics studies of the most potent compound are performed to evaluate interactions between the active compound and binding site.

Investigation of anti-diabetic potential and molecular simulation studies of dihydropyrimidinone derivatives

“…Karimian and co-workers also designed, synthesized and characterized a series of dihydropyrimidinone derivatives as β-glucuronidase inhibitor. Their study also revealed potent activity of one of these derivatives with IC 50 of 31.52 ± 2.5 µM ( 27 ). Our results also revealed potential inhibitory activity of active compound against α-glucosidase.…”

Chiến lược nhắm mục tiêu vào DNA dựa trên cấu trúc các dẫn xuất chalcone mang dị vòng như là tác nhân chống ung thư tiềm năng

“…Đã có nhiều nghiên cứu về dược lý và cải thiện hiệu quả của các loại thuốc chống ung thư cho các mục tiêu điều trị khác nhau (Malik et al, 2021;Nguyen et al, 2021;Phuong et al, 2022). Các phân tử đa dạng, mới lạ, được nhắm mục tiêu để giải quyết các vấn đề về kháng thuốc và tăng hiệu lực hoặc giảm tác dụng phụ của các loại thuốc Daoui et al, 2023;Karimian et al, 2021).…”