Abstract
In this work, a new and efficient strategy to identify pharmacophores and anti-pharmacophores sites in thienopyrimidinone derivatives for antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses is described. We carried out receptor based electrostatic analysis to confirm the electronic, steric and hydrophobic requirements for further modifications. Results showed that the major factors that govern the orientation to antibacterial/antiviral activity were of lipophilicity and presence of tautomerism. In addition, POM analyzed compounds constitute different supplementary attractive active sites that possess significant bioactivity and qualify them as promising candidates that might be responsible to inhibit kinase enzymes. Furthermore, the POM analyses provide substantial idea about the structural features of thienopyrimidinone derivatives in relation to biological activities against disease causing agents. Our results suggest future work on these POM assessed derivatives to evaluate their toxicity in human cells and selectivity which improve activity against cancer causing kinase enzymes by developing target oriented new drugs to save humanity.
The identification of potential combined antibacterial/ antifungal and antitumor pharmacophores sites of 4-12, using POM analyses, is the crucial step in optimization of hits. The POM analyses of thienopyrimidinones 4-12 provide substantial idea about the structural features responsible for their combined antibacterial/antifungal activity and provide guidelines for further modifications, with the aim of improving the activity and selectivity of designed drugs targeting potentially the kinase enzyme responsible of cancer.