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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/24018

Title: Pharmacophore modeling and in silico toxicity assessment of potential anticancer agents from African medicinal plants
Authors: Ntie-Kang, Fidele
Simoben, Conrad Veranso
Karaman, Berin
Ngwa, Valery Fuh
Judson, Philip Neville
Sippl, Wolfgang
Mbaze, Luc Meva'a
Issue Date: 2016
Citation: DRUG DESIGN DEVELOPMENT AND THERAPY, 10, p. 2137-2154
Abstract: Molecular modeling has been employed in the search for lead compounds of chemotherapy to fight cancer. In this study, pharmacophore models have been generated and validated for use in virtual screening protocols for eight known anticancer drug targets, including tyrosine kinase, protein kinase B beta, cyclin-dependent kinase, protein farnesyltransferase, human protein kinase, glycogen synthase kinase, and indoleamine 2,3-dioxygenase 1. Pharmacophore models were validated through receiver operating characteristic and Guner-Henry scoring methods, indicating that several of the models generated could be useful for the identification of potential anticancer agents from natural product databases. The validated pharmacophore models were used as three-dimensional search queries for virtual screening of the newly developed AfroCancer database (similar to 400 compounds from African medicinal plants), along with the Naturally Occurring Plant-based Anticancer Compound-Activity-Target dataset (comprising similar to 1,500 published naturally occurring plant-based compounds from around the world). Additionally, an in silico assessment of toxicity of the two datasets was carried out by the use of 88 toxicity end points predicted by the Lhasa's expert knowledge-based system (Derek), showing that only an insignificant proportion of the promising anticancer agents would be likely showing high toxicity profiles. A diversity study of the two datasets, carried out using the analysis of principal components from the most important physicochemical properties often used to access drug-likeness of compound datasets, showed that the two datasets do not occupy the same chemical space.
URI: http://hdl.handle.net/1942/24018
DOI: 10.2147/DDDT.S108118
ISI #: 000378919700002
ISSN: 1177-8881
Category: A1
Type: Journal Contribution
Validation: ecoom, 2017
Appears in Collections: Research publications

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