In-silico Investigation by Molecular Docking, DFT and Pharmacokinetic Studies of Some Synthesized 1,8-Naphthyridine Derivatives as Prospective Anti-Breast Cancer Agents

Abstract

Abstract Cancer, which has been identified as the second leading causes of health-related mortalities worldwide, is a disease in which some cells of the human body grow uncontrollably and spread to other parts of the body. The resistance of cancer (especially breast cancer) cells to known treatments as well as the adverse side effects associated with current anti-breast cancer drugs necessitates the discovery of novel and potent drug candidates. In this study, in-silico approaches such as DFT studies, Molecular Docking simulation and pharmacokinetic property predictions were used to examine the potency of seventeen (17) previously synthesized novel derivatives of 1,8-naphthyridine as potent anti-breast cancer agents using the Tamoxifen Standard drug (an FDA approved drug for the treatment of breast cancer) as reference. From the molecular docking studies, most of the compounds were found to have better binding energy to the human estrogen receptor (PDB ID: 1ERR) than the control drug (Tamoxifen, Mol. Dock score = −137.807, Re-rank score = −106.527 Kcalmol-1). Compounds C3 and C13 (with Mol. Dock scores -147.054 and -147.819 Kcalmol-1 respectively), which had superior docking scores than the standard drug, were found to be stable based of DFT studies. The predicted drug-likeness and pharmacokinetics properties of these two compounds were also found to be within the acceptable optimal requirements for drug development. Based on the results therefore, compounds C3 and C13 are proposed as potent anti-breast cancer drug candidates with better anti-breast Cancer capacity than the tamoxifen standard drug.