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QSAR studies and design of new analogs of vitamin E with enhanced antiproliferative activity on MCF-7 breast cancer cells

2015; Elsevier BV; Volume: 59; Linguagem: Inglês

10.1016/j.jtice.2015.07.019

1876-1089

Žarko Gagić, Katarina Nikolić, Branka Ivković, Slavica Filipić, Danica Agbaba,

Antioxidant Activity and Oxidative Stress

Vitamin E is group of natural antioxidants comprised of tocopherols and tocotrienols. Structural analogs of vitamin E exhibit selective antiproliferative activity that has been intensively studied over the last decade in various cancer cells (MCF-7, MDA-MB-231, LNCaP, PC-3, A549, K562, Jurkat). 2D- and 3D-QSAR studies were applied on a series of 30 derivatives of tocopherols, tocotrienols and chromane with antiproliferative activity in MCF-7 breast cancer cell line. All molecular structures were previously optimized using ab initio Hartree-Fock/3-21 G method. Partial Least Square Regression analysis was used to develop 2D- and 3D-QSAR model. Statistical parameters: R2 = 0.798, Q2 = 0.772, R2pred = 0.685 (2D-QSAR) and R2 = 0.960, Q2 = 0.830, R2pred = 0.649 (3D-QSAR) indicated on good predictive power of both models. Based on the applied QSAR studies were identified molecular determinant with the greatest influence on the antiproliferative activity and designed novel compounds with enhanced activity against MCF-7 breast cancer cells.