z-logo
Premium
3D‐QSAR Studies on C24‐Monoalkylated Vitamin D 3 26,23‐Lactones and their C2 α ‐Modified Derivatives with Inhibitory Activity to Vitamin D Receptor
Author(s) -
Wang Jinhu,
Tang Ke,
Hou Qianqian,
Cheng Xueli,
Dong Lihua,
Liu Yongjun,
Liu Chengbu
Publication year - 2010
Publication title -
molecular informatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.481
H-Index - 68
eISSN - 1868-1751
pISSN - 1868-1743
DOI - 10.1002/minf.201000071
Subject(s) - quantitative structure–activity relationship , stereochemistry , chemistry , training set , lactone , calcitriol receptor , ligand (biochemistry) , receptor , biochemistry , artificial intelligence , computer science
The ligand‐based three‐dimensional quantitative structure‐activity relationship (3D‐QSAR) for 82 inhibitors of 25‐dehydro‐1 α ‐hydroxyvitamin D 3 ‐26,23‐lactone analogs has been studied by using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. The established CoMFA model in training set gives a cross‐validated q 2 value of 0.516 and a non‐cross‐validated r ncv 2 value of 0.667, while the CoMSIA model results in q 2 =0.517 and r ncv 2 =0.632. In general, the predictive ability of the CoMFA model is superior to that of the CoMSIA model, with r pred 2 =0.639 for the CoMFA and r pred 2 =0.619 for the CoMSIA model. Based on the CoMFA contour maps, some key structural characters of vitamin D 3 analogs responsible for inhibitory activity are identified, and some new C2 α ‐modified 24‐alkylvitamin D 3 lactone analogs with high predicted p IC 50 values are designed. The ligand functional group mutations by FEP simulation and docking studies reveal the rationality of the molecular design.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here