Anti-inflammatory biomolecular activity of chlorinated-phenyldiazenyl-naphthalene-2-sulfonic acid derivatives: perception from DFT, molecular docking, and molecular dynamic simulation
Akaninyene D. Udoikono, Ernest C. Agwamba, Hitler Louis, Innocent Benjamin, Iqrar Ahmad, Emmanuel U. Ejiofor, Eze Frank Ahuekwe, Kelechi Chukwuemeka, Adedapo S. Adeyinka, Harun Patel, Amanda‐Lee E. Manicum, Moses M. Edim
Abstract
In this study, two novel derivatives of naphthalene-2-sulfonic acid: 6-(((1S,5R)-3,5-dichloro-2,4,6-triazabicyclo [z3.1.0]hex-3-en-1-yl)amino)-5-((E)-phenyldiazenyl)naphthalene-2-sulfonic acid (DTPS1) and (E)-6-((4,6-dichloro-1,3,5-triazine2-yl)amino)-4-hydroxy-3-(phenyldiazenyl)naphthalene-2-sulfonic acid (DTPS2) have been synthesized and characterized using FT-IR, UV-vis, and NMR spectroscopic techniques. Applying density functional theory (DFT) at the B3LYP, APFD, PBEPBE, HCTH, TPSSTPSS, and ωB97XD/aug-cc-pVDZ level of theories for the electronic structural properties. In-vitro analysis, molecular docking, molecular dynamic (MD) simulation of the compounds was conducted to investigate the anti-inflammatory potential using COXs enzymes. Docking indicates binding affinity of −9.57, −9.60, −6.77 and −7.37 kcal/mol for DTPS1, DTPS2, Ibuprofen and Diclofenac which agrees with in-vitro assay. Results of MD simulation, indicates sulphonic group in DTPS1 has > 30% interaction with the hydroxyl and oxygen atoms in amino acid residues, but > 35% interaction with the DTPS2. It can be said that the DTPS1 and DTPS2 can induce inhibitory effect on COXs to halt biosynthesis of prostaglandins (PGs), a chief mediator of inflammation and pain in mammals.Communicated by Ramaswamy H. Sarma