In continuing our programme aimed to use
Petra, Osiris and Molinspiration (POM) analyses to search
for potent drugs against multidrug-resistant pathogens
(bacteria and fungi), a series of thirteen peptide alkaloids
from Zizyphus species (PAZ) were POM analysed and
evaluated for their calmodulin-dependent protein kinase-II
(CDPK) inhibition. Results showed that lipophilicity and
presence of (NH-CO) pharmacophore site are the major
factors that governed the orientation in determining antiKinase-II
activity. Furthermore, it was also found that
some of the POM analysed PAZ have a closed pharmacophore
sites which might be responsible for low bioactivity.
To confirm the electronic, steric and hydrophobic
requirements for future modifications, we have also carried
out receptor based electrostatic analysis. Therefore, we
conclude that POM analyses may prove to be a suitable
method to correlate structural features of PAZ with their
promising anti-Kinase-II activity and may contribute to the
development of novel rigid natural analogs of most bioactive
hits 13 (IC
= 2.9 lM) against drug resistant
human cancers.
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