Cancer is the main cause of death and the most significant determinant of life expectancy in every country in the twenty-first century. According to the World Health Organization (WHO) cancer is responsible for major cause of death globally. Benzophenone derivatives are found in a variety of naturally occurring compounds which are known to be pharmacologically efficacious against a variety of diseases, including cancer. Microtubules are thought to be a good target for cancer chemotherapies. Microtubule polymerization and depolymerization are induced by a variety of natural, synthetic, and semisynthetic chemicals having a benzophenone nucleus, affecting tubulin dynamics. Several medications that affect microtubule dynamics are in various stages of clinical trials, including Combretastatins (phase II), Vincristine (clinically approved), Paclitaxel (in clinical usage), and epothilone (phase III), and only a few have been patented. Benzophenone derivatives act by targeting the colchicine binding site of microtubules damage them and cause cell cycle arrest in the G2-M phase. Belonging to this class of molecules, phenstatin, a potent inhibitor of tubulin polymerization, shown strongly inhibited cancer cell growth and arrest the G2/M phase of the cell cycle by targeting the colchicine binding site of microtubules. In the present manuscript we described the benzophenone as tubulin polymerization inhibitors their structure activity relationships (SARs) and molecular docking studies that reveal its binding affinity with the colchicine binding site.
:<strong> </strong>Cancer is one of the fastest-growing epidemics that affect millions yearly. A handful of anticancer drugs are available on the market, but they produce undesirable side effects. Currently, tubulin inhibitors targeting the colchicine binding site are considered an important target due to their structural simplicity and favorable pharmacokinetics with fewer side effects. Different researchers conducted many studies to discover a novel tubulin inhibitor targeting the colchicine binding site with high safety and potency. In the present study, we performed computational analysis of 48 styrylquinolines analogs obtained from literature using different drug designing tools. The pharmacophore mapping study was conducted to identify the important pharmacophoric features essential for biological activity. Atom-based 3D-QSAR (3-dimensional quantitative structure-activity relationship) analysis was carried out to know the contribution of different atoms to model development. The generated model showed a statistically significant coefficient of determinations for the training and test sets. The best QSAR model was selected based on R<sup>2</sup> (0.8624) and Q<sup>2</sup> (0.6707) values. Contour plot analysis of the developed model unveiled the chemical features necessary for tubulin inhibition. A docking study was performed on potent styrylquinoline analog 9VII-f(46), which shows the highest SP docking scores (-5.494). ADME (Absorption, distribution, metabolism, and excretion) analysis provides valuable information about the drugability of newly designed compounds.
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