  Structures and minimum molecular electrostatic potential (MEP) distributions
in anacardic acid and some of its derivatives have been studied by full
geometry optimization at the M06-2X/6-31G(d,p), WB97XD/6-31G(d,p) and
B3LYP/6-31G(d,p) levels of density functional theory (DFT) in gas phase as well
as in DMSO and aqueous solutions. Solvent effect was treated employing the
integral equation formalism of the polarizable continuum model. Effects of
modifications of the C1-side chain on the minimum MEP values in various regions
were studied. Minimum MEP values near the oxygen atoms of the C2-OH group,
oxygen or sulfur atoms of the C1-attached urea or thiourea groups and above or
below the ring plane considered to be involved in interaction with the receptor
were used to perform multiple linear regression. Experimentally observed
anti-bacterial activities of these molecules against S. aureus are thus shown
to be related to minimum MEP values in the above mentioned regions. Among the
three DFT functionals used in the study, the M06-2X functional is found to
yield most reliable results. Anti-bacterial activities have been predicted for
certain molecules of the class which need to be verified experimentally.
