Comparative molecular docking of antitrypanosomal natural products into multiple Trypanosoma brucei drug targets.
Antitrypanosomal natural products with different structural motifs previously shown to have growth inhibitory activity against Trypanosoma brucei were docked into validated drug targets of the parasite, which include trypanothione reductase, rhodesain, farnesyl diphosphate synthase, and triosephosphate isomerase. The in-silico calculations predicted that lowest energy docked poses of a number of the compounds can interact with catalysis-dependent residues, thus making them possible catalytic inhibitors and of course physiologically active. Compounds that possess a number of hydrogen-bond-accepting and/or -donating groups like phenolics and quinones show extensive interactions with the targets. Compounds like cissampeloflavone, 3-geranylemodin and ningpogenin thus offer profound promise.
Ogungbe
Ifedayo V
IV
Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA. dayovictor2000@yahoo.com
Setzer
William N
WN
D000818:Animals; D001665:Binding Sites; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D003198:Computer Simulation; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D055808:Drug Discovery; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry / Q000378:metabolism; D051228:Geranyltranstransferase / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D015394:Molecular Structure; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D014305:Triose-Phosphate Isomerase / Q000737:chemistry / Q000378:metabolism; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei / Q000737:chemistry / Q000187:drug effects; D014353:Trypanosomiasis, African / Q000188:drug therapy
D001688:Biological Products; D014344:Trypanocidal Agents; D005182:Flavin-Adenine Dinucleotide; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D051228:Geranyltranstransferase; D003546:Cysteine Endopeptidases; C446033:rhodesain; D014305:Triose-Phosphate Isomerase