In silico pharmacokinetic and molecular docking studies of n-cinnamoyltetraketide derivatives as inhibitors of cyclooxygenase-2 enzyme

Authors

Stephen S. Nyandoro, Chemistry Department, College of Natural and Applied Sciences, University of Dar es Salaam, P.O.Box 35061, Dar es Salaam, Tanzania.Follow
Daniel M. Shadrack, St. John’s University of Tanzania, Chemistry Department, P.O.Box 47, Dodoma, Tanzania.Follow
Joan J. E. Munissi, Chemistry Department, College of Natural and Applied Sciences, University of Dar es Salaam, P.O.Box 35061, Dar es Salaam, Tanzania.Follow
Egid B. Mubofu, Chemistry Department, College of Natural and Applied Sciences, University of Dar es Salaam, P.O.Box 35061, Dar es Salaam, Tanzania.Follow

Section

Biological Sciences

Abstract

Recent phytochemical analysis of Toussaintia orientalis leaves yielded series of novel bioactive N-cinnamoyltetraketide derivatives namely toussaintines A-G (t_1 - t_8) some portraying cytotoxicity against the triple negative aggressive human breast cancer cell line (MDA-MB-231) among other potencies. Despite having broad bioactivity spectrum, their general drug-likeness profiles and mode of action (simulated or actual) targeting any enzyme remains uninvestigated. In silico pharmacokinetic, drug-likeness descriptors and molecular docking of the compounds t_1-t_8 targeting inhibition of cyclooxygenase-2 (COX-2) enzyme were evaluated. The Lipinski Rule of Five heralded the pharmacokinetic properties of the studied metabolites. The studied compounds were docked with COX-2 following already established protocol. ADMET descriptors fell within the recommended range, except for compound t_3 that was predicted to potentially have positive blood brain barrier (BBB+) penetration. Docking studies indicated N-cinnamoyltetraketide derivatives as potential inhibitors of COX-2 enzyme.  Compounds t_3 and t_5 showed lower binding energy of -13 and -12.3 kcal/mol, respectively, being closely comparable to celecoxib (-12.3 kcal/mol) indicating compatibility with the protein receptor. The findings provide baseline information on drug or lead-likeness and potential mode of action of the studied molecules towards inhibition of COX-2 enzyme.

Recommended Citation

Nyandoro, Stephen S.; Shadrack, Daniel M.; Munissi, Joan J. E.; and Mubofu, Egid B. (2018) "In silico pharmacokinetic and molecular docking studies of n-cinnamoyltetraketide derivatives as inhibitors of cyclooxygenase-2 enzyme," Tanzania Journal of Science: Vol. 44: Iss. 2, Article 1.
Available at:https://doi.org/10.65085/2507-7961.1743