In silico pharmacokinetic, molecular docking and molecular dynamics simulation studies of n-cinnamoyltetraketide derivatives as inhibitors of cyclooxygenase-2 enzyme
| dc.contributor.author | Nyandoro, Stephen S. | |
| dc.contributor.author | Shadrack, Daniel M | |
| dc.contributor.author | Munissi, Joan J.E | |
| dc.contributor.author | Mubofu, Egid B. | |
| dc.date.accessioned | 2018-11-08T10:10:06Z | |
| dc.date.available | 2018-11-08T10:10:06Z | |
| dc.date.issued | 2018-06 | |
| dc.description.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 | en_US |
| dc.identifier.citation | Stephen S. Nyandoro, Daniel M. Shadrack, Joan J.E. Munissi, Egid B. Mubofu, In silico pharmacokinetic, molecular docking and molecular dynamics simulation studies of n-cinnamoyltetraketide derivatives as inhibitors of cyclooxygenase-2 enzyme, Tanzania Journal of Science. 2018, 44, (2), 1-15 | en_US |
| dc.identifier.issn | 0856-1761 | |
| dc.identifier.uri | http://hdl.handle.net/20.500.11810/4966 | |
| dc.language.iso | en | en_US |
| dc.publisher | Dar es Salaam University Press | en_US |
| dc.subject | N-cinnamoyltetraketide derivatives; molecular docking, ADMET, in silico, COX-2. | en_US |
| dc.title | In silico pharmacokinetic, molecular docking and molecular dynamics simulation studies of n-cinnamoyltetraketide derivatives as inhibitors of cyclooxygenase-2 enzyme | en_US |
| dc.type | Journal Article | en_US |