On thorough literature search, it was found that this scaffold was never utilized for any exploration towards anti-inflammation studies. Therefore, the cyclooxygenase-2 (COX-2) (the most prominent enzyme responsible for aggravating inflammation) inhibitory potential of a few well-known compounds of cyclopenta[a]phenanthrene scaffold were in-silico studied. The present study involved exploration of anti-inflammatory potentials of some of the 10,13-dimethyl-6-methylheptan-2-yl)-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl) derivatives; (R,3E,7E)-((3R,10R,13R,14R)-10,13-dimethyl-17-((S)-6-methylheptan-2-yl)- 2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl) -5-hydroxy-3-methyl-9-methyleneundeca-3,7-dienoate (1), (E)-((3R,10R,13R,14R)-10,13-dimethyl-17-((S)-6-methylheptan-2-yl)-2,3,4,7,8,9, 10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-6-oxooct-4-enoate (2) and (S)-1-((3R,10R,13R,14R) -10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a] phenanthren -3-yl)-5-methyl-3-((R,E)-1-amino-3-ethyl-6-oxohept-3-enyl)pentanedioate (3) by molecular docking technique utilizing the Glide module of Maestro 9.1 software using the celecoxib bound PDB file of COX-2 (PDB ID: 3LN1). All the three derivatives have a higher perspective of acting as potent COX-2 inhibitor as revealed by high Glide Score. The IFD results showed that inhibitor 1 had the highest Glide score of -9.13 Kcal/mol compared to other inhibitors. The good binding affinity of this inhibitor may be due to the various interactions such as hydrogen bonding, interactions of hydrophobic, hydrophilic, electrostatic and steric origin. The compound significantly demonstrated hydrogen bonding with four amino acid residues of the active site; His183, Gln423, Asn351 and Thr181. This study opened several avenues of research, betterment and future directions of upbringing the scaffold based inhibitors in the near future.
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