Akademik Veri Yönetim Sistemi
ChemistrySelect, cilt.9, sa.37, 2024 (SCI-Expanded)
In the present work, we performed a computational study on hydroxamic acid containing compounds as acid sphingomyelinase (ASM) inhibitors. The study starts from the development of 3D-QSAR and pharmacophore models, which were further taken as a source for the enumeration and virtual screening study. The 3D-QSAR results showed the best statistical model with Q2, R2, and R2 scrambling values of 0.7175, 0.9019, and 0.7128, respectively. The pharmacophore hypothesis generated one of the best hypotheses including five features such as 2 aromatic rings, 2 hydrogen bond donors, and 1 hydrogen bond acceptor. The enumeration study paved the path in the discovery of novel compounds where pharmacophore hypothesis and 3D QSAR study data was used for the identification of novel compounds. Compound 9f_20 showed good docking score −11.399 and binding interactions with amino acids HIP317, ASN316, GLH386, Zn701, Zn702, HIP317, and HIP280 required for ASM inhibitory activity. The virtual screening study was performed on the basis of developed pharmacophore ADDRR_1 where ZINC000013941849 showed good binding interactions with receptor including amino acids Zn701, Zn702, HIP280, LYS103, HIP317, ASN316, and ILE487. ZINC000013941849 with docking score −13.101. The screened compounds may be taken for the further development of novel antidepressant agents.