194-201A series of griseofulvin analogues has been
examined to determine the structural requirements of antifungal activity by three-dimensional
quantitative structure-activity relationship studies using comparative molecular
field analysis (CoMFA) and comparative molecular similarity indices analysis
(CoMSIA ) methods. Evaluation of 22 compounds (training set) has established the
CoMFA and CoMSIA models, which have been validated by evaluation of a set of four
compounds (test set). The lowest energy conformer of the most active molecule
obtained from systematic search has been used as the template structure for the
alignment. In this study, the superimposition of molecules was carried out by atom-based
fit (rms), multi fit and field fit. Along with steric and electronic fields, ClogP
has been taken as additional descriptor to account for lipophilicity. Further,
a QSAR analysis has been carried out using Tools for Structure-Activity Relationship
software. For this study, various chemical descriptors such as electronic, steric,
lipophilic, topological have been calculated and multiple regression carried out.
The QSAR models from these three methods exhibit considerable correlative and predictive
properties. The models obtained from the present study may be useful for the development
of new griseofulvin analogues as potential antifungals