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QSAR STUDIES ON ANTIMICROBIAL ACTIVITY OF BENZOXAZINDIONE ANALOGUES

Recently, different benzoxazindione analogues were investigated for their antiviral, tocolytic oxytocin receptor activity, and in treatment of allergic condition. Antiretroviral drug, efavirenz, approved as a non-nucleoside reverse transcriptase inhibitor is also analogue of benzoxazinone, i.e. 6-chloro-4-(cyclopropylethynyl)-1, 4-dihydro-4-(trifluoromethyl)-2H-3, 1-benzoxazin-2-one. The progress in chemical graph theory and topology has revealed their applicability to practically all areas of chemistry, particularly medicinal chemistry, by successful predictions of physico-chemical properties and biological activities of molecules proceeding from molecular structure. As an extension of our earlier studies in attempting the role of the use of topological indices (TIs) for QSAR studies, the quantitative structure-activity relationship (QSAR) of 1, 4-benzoxazin-2, 3-dione and 3, 1-benzoxazin-2, 4-dione analogues were studied using computed molecular descriptors (MDs) and experimentally obtained parameters for antimicrobial activity (MIC). Biological activity were evaluated using 7 test microorganisms, i.e. three G(+), three G(-) bacteria, and Candida monosa. Previous QSAR studies with involvement of only topological indices, TIs (W, X1, J) have shown significant correlation between antimicrobial activity (MIC) and TIs. In this study additional TIs and other MDs were explored (CID, X1, XMOD, VRA1, BID, Sv, Se and ALOGP) using multiple linear regression techniques. Present results are in good agreement with previously obtained and give the preference of biological predictability on the basis of two or more TIs. This approach allows investigation of influence more than one TI on particular system such as combination of constitutional descriptors (Sv, Se, ..), topological descriptors (ISIZ, MV1, … ), molecular properties (ALOGP, MLOGP) and other known descriptors. Good correlation was observed using constitutional (Sv) and topological (ZM1V) descriptors and antimicrobial activity (MIC) towards Klebsiella pneumoniae. References: 1. F. R. Calabri, et al., Eur. J. Med. Chem. 40 (2005) 897-907. USP 7, 056, 914 (J. Torrens, et al., 2006) 2. EP1122245, http://www.freepatentsonline.com/EP1122245B1.html 3. M. Movrin, M. Jadrijević-Mladar, D. Maysinger ; Acta Pharm. Jugosl. 35 (1985) 193-202. 4. M. Movrin, M. Jadrijević-Mladar ; Pharmazie 38 (H. 12) (1983) 883-885.

QSAR; benzoxazindiones; antimicrobial activity; molecular descriptors; topological descriptors; 2D and 3D correlations

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