Premium
Pharmacophore Identification and Validation Study of CK2 Inhibitors Using CoMFA/CoMSIA
Author(s) -
Morshed Mohammad Neaz,
Muddassar Muhammad,
Pasha Farhan Ahmad,
Cho Seung Joo
Publication year - 2009
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2009.00841.x
Subject(s) - pharmacophore , quantitative structure–activity relationship , chemistry , stereochemistry , computational biology , similarity (geometry) , casein kinase 1 , molecular model , kinase , biology , biochemistry , protein kinase a , computer science , artificial intelligence , image (mathematics)
Protein kinase CK2, also known as casein kinase‐2, has been found to be involved in cell growth, proliferation and suppression of apoptosis, which is related to human cancers. The series of compounds were identified as casein kinase‐2 inhibitors and their inhibitory activities are a function of a variation of their structures. The current study deals with the pharmacophore identification and, accordingly, the three‐dimensional quantitative structure–activity relationship model development using Pharmacophore Alignment and Scoring Engine. Several hypotheses were developed for the molecular alignments. On the basis of statistical values, the best‐fitted model was identified and the same alignment was used for 3D‐QSAR using comparative molecular field analysis/comparative molecular similarity index analysis. Both the CoMFA ( R 2 CV = 0.58, R 2 = 0.82 and r 2 pred = 0.62) and the comparative molecular similarity index analysis ( R 2 CV = 0.74, R 2 = 0.98 and r 2 pred = 0.81) gave reasonable results. Besides pharmacophore‐based alignment, the maximum common substructure‐based alignment was also used for the comparative molecular field analysis and comparative molecular similarity index analysis. The pharmacophore‐based alignment was more prominent and it has provided important information for the modelling of potent inhibitors. The overall study implies that a highly positive and bulky group with H‐bond donating property is desirable around the nitrogen atom adjacent to the pyrrolidine ring.