Synthesis, Molecular Docking and Molecular Dynamics Simulation Studies of Some Pyridazinone Derivatives as Lipase Inhibitors

Cumhuriyet Science Journal

article

Mehmet Abdullah ALAGÖZ¹  İnci Selin DOĞAN²  Sıla SENER³  Zeynep ÖZDEMİR⁴ 

[1] INONU UNIVERSITY;KARADENİZ TEKNİK ÜNİVERSİTESİ;SAĞLIK BİLİMLERİ ÜNİVERSİTESİ;İNÖNÜ ÜNİVERSİTESİ

关键词: Pyridazinone;    Molecular docking;    Molecular dynamics simulations studies;    Lipase inhibition.;   

DOI  :  10.17776/csj.1135400

学科分类：工程和技术（综合）

来源: Cumhuriyet University

【 摘 要 】

Human health and illness are dependent on lipases, which play a key role in maintaining cell integrity, storing fat for energy and serving as signaling molecules. In this study, 4 compounds that carry 6-phenylpyridazin-3(2H)-one main nucleus, which can be effective as lipase inhibitors, were synthesized and their structures were elucidated. The biological activity of synthesized compounds was evaluated via the porcine pancreatic lipase type II (PLL) inhibitor assay. Orlistat, a lipase inhibitor, was used as a positive control. Compound 8d was found to be the most effective compound, with an IC50 value of 32.66±2.8265 (μg/mL). In addition, molecular docking and molecular dynamics simulations studies were carried out to examine the interactions of the compounds with the target in detail. The results obtained as a result of these in silico studies were found to be compatible with the lipase inhibition effects of the compounds. It was observed that the compounds may have potential lipase inhibitory effects as a result of the substitutions of the 3-(6-oxo-3-phenylpyridazin-1(6H)-yl)propanehydrazide structure.

【 授权许可】

CC BY-NC-ND