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 αIIbβIII 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.
Department of Biotechnology, Punjab University, Chandigarh, India.
Sajad
S
Shahbazi
Centre for System Biology and Bioinformatics, Punjab University, Chandigarh, India.
Tammanna R
TR
Sahrawat
Centre of Biotechnology, Siksha O Anusandhan University, Khandagiri, Bhubaneswar, Odisha, India.
Monalisa
M
Ray
Centre of Biotechnology, Siksha O Anusandhan University, Khandagiri, Bhubaneswar, Odisha, India.
Swagatika
S
Dash
Centre of Biotechnology, Siksha O Anusandhan University, Khandagiri, Bhubaneswar, Odisha, India.
Dattatreya
D
Kar
Centre of Biotechnology, Siksha O Anusandhan University, Khandagiri, Bhubaneswar, Odisha, India.
Shikha
S
Singh
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D001665:Binding Sites; D002109:Caffeic Acids / Q000627:therapeutic use; D000068579:Celecoxib / Q000627:therapeutic use; D003373:Coumaric Acids / Q000627:therapeutic use; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D000072237:ERG1 Potassium Channel / Q000378:metabolism; D005054:Eugenol / Q000031:analogs & derivatives / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D039421:Integrin alpha2 / Q000378:metabolism; D017434:Protein Structure, Tertiary; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D002109:Caffeic Acids; D003373:Coumaric Acids; D000072237:ERG1 Potassium Channel; C056564:ITGA2B protein, human; D039421:Integrin alpha2; C000606913:KCNH2 protein, human; D005054:Eugenol; D014443:Tyrosine; C036643:isoeugenol; C004999:ferulic acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000077466:Tirofiban; D000068579:Celecoxib; D001241:Aspirin; C040048:caffeic acid