Modeling studies on phospholipase A2-inhibitor complexes.

Phospholipase A2 (PLA2) is a ubiquitous enzyme that specifically catalyzes hydrolysis of membrane phospholipids to produce lysophospholipids and free fatty acid, namely arachidonic acid, which provides substrate for eicosanoids biosynthesis. Thus, the compounds inhibiting PLA2 have been implicated as potential therapeutic agents in treatment of inflammation related diseases. Plant and marine organisms serve as sources of compounds that act as potential therapeutic agents for treatment of various diseases. The present study reveals the relationship between the structure and function of the medicinally important herbal compounds (acalyphin, chlorogenic acid, stigmasterol, curcumin and tectoridin) and marine compounds (gracilin A and aplysulphurin A). To understand the binding mechanisms of these compounds, molecular modeling studies has been performed with Russell's viper and bovine pancreatic PLA2 as target molecules using molecular operating environment (MOE) software. These compounds show favorable interactions with the amino acid residues at the active site of Russell's viper and bovine pancreatic PLA2, thereby substantiating their proven efficacy as anti-inflammatory compounds and antidotes.

Quantitative structure-activity relationship of some pesticides.

Herbicides (benzodiazepinediones), insecticides (dioxatricyclododecenes) and larvicides (N-oxalyl derivatives of tebufenozide) have been quantitatively investigated to explore the relationship between the molecular structure and their biological activity using molecular operating environment (MOE) software. The study provides good predictive models, cross-validated by leave-out-one method (Loo). The positive contribution of the descriptor n-O (count of oxygen atom) suggests the additional oxygen atom substitution at R1 position, in addition to benzodiazepine moiety is favorable for herbicidal activity, whereas the negative contribution of y component of dipole moment (Dip(y)) indicates that electronic interactions are also crucial for the activity. The negative correlation of V(SA)2 and globularity (Glo) descriptors clearly indicates that the volume, shape, and rigidity of tebufenozide derivatives determine their larvicidal activity. The biparametric model for insecticides shows that the indicator variable l(CH-CH3) and R(PC) (negative partial charge) are detrimental for its activity. Most of the active compounds in the series have shown less value for these descriptors. The derived QSAR models also provide valuable insights to optimize their toxicity, which remains a major concern for environment safety.