MOLECULAR STRUCTURAL PARAMETERS IN TUBERCULOSTATIC ACTIVITY OF POLYHYDROXYXANTHONES

Document Type : Original Article

Authors

Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt

Abstract

This investigation was undertaken to test the correlation of the observed tuberculostatic activity of a series of 7(2)-polyhydroxyxanthones 1a-j with their lipophilic parameters (Rm) as well as molecular orbital descriptors such as; dipole moment (dp); electro density (D); heat of formation (hf), torsion angle (tor); van der Waal forces (vdw), bond length (str) and bond angle (bnd). The Rm-values were calculated from the corresponding Rf­-values, determined using polyamide plates. The molecular orbital regressors were derived through semi-empirical calculations using MMX-computer program.
QSAR analysis of the activity parameters (Ka, Log Ka, Ka* and logKa*) as dependent variables and Rm or combination of Rm and dummy parameters representing the substitution pattern of hydroxyl groups on ring C of the xanthone nucleus demonstrated an increase in the lipophilic character by itself which did not correlate (r» -0.42) with increased potency against Mycobacterium lufu. Permeability study using standard cellophane membrane showed that, the synthesized compounds were poorly penetrating and may act directly on the cell wall. On the contrary higher correlation (r= 0.91) was observed between the activity parameter (log Ka*) and the electron density at C-4.

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