STRUCTURE-ACTIVITY-RELATIONSHIPS OF SOME ANTIMICROBIAL 5-SUBSTITUTED 2-(3-PYRIDYL) BENZOXAZOLES USING QUANTUM-CHEMICAL CALCULATIONS

The synthesis and in vitro antimicrobial activity of 5-substituted 2-( 3-pyridyl)benzoxazoles (3-7) is described for some Gram-positive and G ram-negative bacteria and the yeast Candida albicans. The compounds 3- 7 exhibited significant activity against the screened microorganisms, having MIC values between 25 and 12.5 mu g/ml. Quantum-chemical calcul ations were performed for the compounds 1-10, in order to observe some feasible structure-activity relationships. These theoretical observat ions, calculated for the description of the mechanism of interactions at the molecular level, revealed that the electrophilic superdelocaliz ability of the nitrogen atom (S-N(E)) in the oxazolo moiety of the ben zoxazole ring is related to the activity. The results obtained from th e theoretical calculations and the observed MIC values shaw that 2-(3- pyridyl)- and 2-phenylbenzoxazole derivatives exhibit bio-isosteric ef fects for antimicrobial activity. Additionally, substituents at positi on 5 on the fused heterocyclic system contribute to the activity const ructively or destructively depending on the type of microorganism scre ened.