TY - JOUR AU - Samuel Metibemu, Damilohun TI - vHTS and 3D-QSAR for the Identification of Novel Phyto-inhibitors of Farnesyltransferase: Validation of Ascorbic Acid inhibition of Farnesyltransferase in an Animal Model of Breast Cancer SN - 2194-9379 SN - 2194-9387 PY - 2021 JO - Drug Res (Stuttg) JF - Drug Research LA - EN VL - 71 IS - 06 SP - 341 EP - 347 DA - 2021/04/16 KW - Farnesyltransferase KW - Virtual high throughput screening KW - 3D-QSAR KW - Ascorbic acid KW - 7 KW - 12-dimethylbenz(a)anthracene (DMBA) AB - Farnesyltransferase (FTase) is a zinc enzyme that has been the subject of attention in anti-cancer research over the past. In this study, phytochemicals from Curcuma longa L., Taraxacum officinale, and Spondias mombin plants were screened for their inhibitory potentials on the human farnesyltransferase. A three-dimensional quantitative structure-activity relationship (3D-QSAR) model for the inhibition of farnesyltransferase was generated and the inhibition of farnesyltransferase by the hit, ascorbic acid was validated in an animal model of breast cancer. The lead compound, ascorbic acid makes extensive hydrogen bond interactions with key residues, lys-353, tyr-300, gly-290, leu-290 within the active site of farnesyltransferase. It downregulated the expression of FNTA mRNA in an animal model of breast cancer. The 3D-QSAR generated herein is robust, thoroughly validated, and should be employed in the pipelining of novel farnesyltransferase inhibitors. Ascorbic acid demonstrates its anticancer potentials through the inhibition of farnesyltransferase. PB - Georg Thieme Verlag KG DO - 10.1055/a-1422-1885 UR - http://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-1422-1885 ER -