Design and QSAR study of analogs of gamma-tocotrienol with enhanced anti proliferative activity against human breast cancer cells
Abstract
Quantitative structure-activity relationships (QSAR) study has been performed for two sets of the antitumor drugs against human breast cancer MCF-7 cell lines, alpha-tocopherol and cholesterol derivatives. Constitutional, geometrical, physico-chemical and electronic descriptors (using the density functional theory, B3LYP/6-31G (d,p) basis set) were computed and analyzed. The most relevant of these descriptors were grouped and multiple linear regressions have been carried out. Optimal QSAR models with three and four variables, R-2 > 0.95 and cross-validation parameter q(pre)(2) > 0.88, were selected. Based on the QSAR study, novel vitamin-E derivatives (compounds D-1 and D-2) were designed and their antiproliferative activities were evaluated using the proposed regression models. Calculated antiproliferative activities of the designed compounds, IC50 (D-1): 3.09 mu M and IC50 (D-2): 3.54 mu M, were significantly stronger than anticancer effect of the other analyzed compounds IC50: 4-146...1 mu M.
Keywords:
QSAR / alpha-Tocopherol / gamma-Tocotrienol / Cholesterol / Lysine / Human breast cancerSource:
Journal of Molecular Graphics & Modelling, 2009, 27, 7, 777-783Publisher:
- Elsevier Science Inc, New York
Funding / projects:
- Sinteza, kvantitativni odnosi između strukture/osobina i aktivnosti, fizičko-hemijska karakterizacija i analiza farmakološki aktivnih supstanci (RS-MESTD-MPN2006-2010-142071)
DOI: 10.1016/j.jmgm.2008.11.007
ISSN: 1093-3263
PubMed: 19117779
WoS: 000265008500003
Scopus: 2-s2.0-61549132609
Collections
Institution/Community
PharmacyTY - JOUR AU - Nikolić, Katarina AU - Agbaba, Danica PY - 2009 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1224 AB - Quantitative structure-activity relationships (QSAR) study has been performed for two sets of the antitumor drugs against human breast cancer MCF-7 cell lines, alpha-tocopherol and cholesterol derivatives. Constitutional, geometrical, physico-chemical and electronic descriptors (using the density functional theory, B3LYP/6-31G (d,p) basis set) were computed and analyzed. The most relevant of these descriptors were grouped and multiple linear regressions have been carried out. Optimal QSAR models with three and four variables, R-2 > 0.95 and cross-validation parameter q(pre)(2) > 0.88, were selected. Based on the QSAR study, novel vitamin-E derivatives (compounds D-1 and D-2) were designed and their antiproliferative activities were evaluated using the proposed regression models. Calculated antiproliferative activities of the designed compounds, IC50 (D-1): 3.09 mu M and IC50 (D-2): 3.54 mu M, were significantly stronger than anticancer effect of the other analyzed compounds IC50: 4-1461 mu M. PB - Elsevier Science Inc, New York T2 - Journal of Molecular Graphics & Modelling T1 - Design and QSAR study of analogs of gamma-tocotrienol with enhanced anti proliferative activity against human breast cancer cells VL - 27 IS - 7 SP - 777 EP - 783 DO - 10.1016/j.jmgm.2008.11.007 ER -
@article{ author = "Nikolić, Katarina and Agbaba, Danica", year = "2009", abstract = "Quantitative structure-activity relationships (QSAR) study has been performed for two sets of the antitumor drugs against human breast cancer MCF-7 cell lines, alpha-tocopherol and cholesterol derivatives. Constitutional, geometrical, physico-chemical and electronic descriptors (using the density functional theory, B3LYP/6-31G (d,p) basis set) were computed and analyzed. The most relevant of these descriptors were grouped and multiple linear regressions have been carried out. Optimal QSAR models with three and four variables, R-2 > 0.95 and cross-validation parameter q(pre)(2) > 0.88, were selected. Based on the QSAR study, novel vitamin-E derivatives (compounds D-1 and D-2) were designed and their antiproliferative activities were evaluated using the proposed regression models. Calculated antiproliferative activities of the designed compounds, IC50 (D-1): 3.09 mu M and IC50 (D-2): 3.54 mu M, were significantly stronger than anticancer effect of the other analyzed compounds IC50: 4-1461 mu M.", publisher = "Elsevier Science Inc, New York", journal = "Journal of Molecular Graphics & Modelling", title = "Design and QSAR study of analogs of gamma-tocotrienol with enhanced anti proliferative activity against human breast cancer cells", volume = "27", number = "7", pages = "777-783", doi = "10.1016/j.jmgm.2008.11.007" }
Nikolić, K.,& Agbaba, D.. (2009). Design and QSAR study of analogs of gamma-tocotrienol with enhanced anti proliferative activity against human breast cancer cells. in Journal of Molecular Graphics & Modelling Elsevier Science Inc, New York., 27(7), 777-783. https://doi.org/10.1016/j.jmgm.2008.11.007
Nikolić K, Agbaba D. Design and QSAR study of analogs of gamma-tocotrienol with enhanced anti proliferative activity against human breast cancer cells. in Journal of Molecular Graphics & Modelling. 2009;27(7):777-783. doi:10.1016/j.jmgm.2008.11.007 .
Nikolić, Katarina, Agbaba, Danica, "Design and QSAR study of analogs of gamma-tocotrienol with enhanced anti proliferative activity against human breast cancer cells" in Journal of Molecular Graphics & Modelling, 27, no. 7 (2009):777-783, https://doi.org/10.1016/j.jmgm.2008.11.007 . .