Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies.

Cyclooxygenase-2 (COX-2) plays an important role in memory consolidation and synaptic activity, the most fundamental functions of the brain. It converts arachidonic acid to prostaglandin endoperoxide H2. In contrast, if over-expressed, it causes inflammation in response to cytokine, pro-inflammatory molecule, and growth factor. Anti-inflammatory agents, by allosteric or competitive inhibition of COX-2, alleviate the symptoms of inflammation. Coxib family drugs, particularly celecoxib, are the most famous anti-inflammatory agents available in the market showing significant inhibitory effect on COX-2 activity. Due to high cardiovascular risk of this drug group, recent researches are focused on the investigation of new safer drugs for anti-inflammatory diseases. Natural compounds, particularly, phytochemicals are found to be good candidates for drug designing and discovery. In the present study, we performed in silico studies to quantitatively scrutinize the molecular interaction of curcumin and its structural analogs with COX-2, COX-1, FXa and integrin αIIbßIII to investigate their therapeutic potential as a cardiovascular-safe anti-inflammatory medicine (CVSAIM). The results of both ADMET and docking study indicated that out of all the 39 compounds studied, caffeic acid had remarkable interaction with proteins involved in inflammatory response. It was also found to inhibit the proteins that are involved in thrombosis, thereby, having the potential to be developed as therapeutic agent.

Conformational study of poly-DeltaAbu peptides and construction of amphipathic nanostructure.

Generally, it is believed that alpha,beta-dehydroamino acid residues are most stable in the Z- form rather than in the E- form. In this study, it has been shown that poly-DeltaAbu exists in alternate Delta(E)Abu and Delta(Z)Abu form, with phi, psi values of approximately 0 degrees , 80 degrees and 35 degrees , 27 degrees for the E- and Z- forms, respectively, rather than the all Z- form. The conformational results for the peptides Ac-DeltaAbu(2)-NHMe and Ac-L/D-Ile-Delta(Z)Abu/Delta(E)Abu-NHMe suggest the incorporation of DeltaAbu in both the Z- and E- forms, which is consistent with the available observations in natural systems. Because of adoption of phi, psi values corresponding to the collagen type structure ( approximately -30 degrees , 120 degrees ) by Ile residue and with phi, psi values in the left-handed helical region for Delta(Z)Abu residue, the peptide Ac-(L-Ile-Delta(Z)Abu)(3)-NHMe adopts an amphipathic left-handed helical beta-sheet type structure. This structure is stabilized by network of hydrogen bonding, carbonyl-carbonyl, and CH-O interactions and can be exploited for the construction of antimicrobial peptides and nanomaterials.