QSAR study on antibacterial and antifungal activities of some 3,4- disubstituted-1,2,4-oxa(thia)-diazole-5(4 H)-ones(thiones) using physicochemical, quantumchemical and structural parameters

This work demonstrated the quantitative structure-activity relationships of 3,4-disubstituted-1,2,4-oxa(thia)-diazole-5(4 H)-ones (thiones) using quantum chemical parameter R(I), hydrophobicity descriptor and structural parameters. Semiempirical molecular orbital calculations were used to determine the quantum chemical parameter R(I), which is the electron density of HOMO at the sulfur and oxygen in position 1 of the compounds investigated, divided by the orbital energy of HOMO. It was shown that the electron density of HOMO at the sulfur and oxygen of the molecules was strongly related to the biological activities of these molecules. The results obtained from the QSAR application indicated that there was a parabolic dependence between the biological activities and the R(I) index. The structural factor I(Y) which shows the presence of a sulfur atom in position 1 was the dominant predictor for the antibacterial and antifungal activities. On the other hand, the other structural variable I(X) which shows the presence of a sulfur atom double bonded to the C atom in position 5 caused a decrease, but the hydrophobicity of the whole molecule (Σ) caused an increase in activity.