Structural exploration and study of the QSAR properties of several series of macrolide antibiotics.

Abstract

In this work a fundamental and original research on the 14- membered macrolide, the aim is to predict the reactivity and biological activity of the compound studied and its derivatives. The molecular modeling methods used in our work are: MM+, PM3 and ab initio/HF(STO- 3G). These methods were used to determine the structural parameters, electronics and energy associated with molecules studied. The nature of such substituent (donor, acceptor) affects the electronic and energy parameters of basic core of the 14- membered macrolide. Indeed, this qualitative study allows us to predict the chemical reactivity of derivatives of the 14- membered macrolide and also the ketolides. A study of structure - property relationships (SPR) forthe 14- membered macrolide derivatives has been carried out for a series of bioactive derivatives of the 14- membered macrolide. QSAR studies have been performed on fifty molecules of the 14- membered macrolide as the antibiotics, multiple linear regression analysis was performed to derive QSAR models which were further evaluated internally for the prediction of activity. The developed models were cross-validated by the ‘leave one out’ technique as well as by the calculation of statistical parameters LOO. High correlation between experimental and predicted activity values was observed, indicating the validation and the good quality of the derived QSAR models