Abstract
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 anti-Kinase-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
50
= 2.9 µM) against drug resistant human cancers.