synthesis and bioligical evaluation of substituted indore derivatives
The indole core is nearly one of the most important heterocycles in nature. Due to the presence of versatile biologically active indoles, the indole moiety has been considered as an essential structural component in a lot of pharmaceutical agents. The high resistance and great side effects of the currently used antitumor drugs have led to an increasing demand for the synthesis of new derivatives with anticipated antitumor activity having fewer side effects and less resistance. Accordingly, the present investigation deals with the synthesis of 3-(1H-indol-2-yl)aniline I, N-[3-(3-formyl-1H-indol-2-yl) phenyl] acetamide VII and 1H-indole-3-carbaldehyde XIII as key intermediates for the preparation of novel indole based nucleus I-XVIII. All of the synthesized compounds (twenty eight) were tested for their antitumor activities against MCF-7 cell line while twelve compounds were screened against A549 cell line in a preliminary testing in NCI of Egypt using sorafenib as a reference standard. Twenty three of these compounds were chosen by the NCI in Bethesda for testing their cytotoxic activities against 60 tumor cell lines. A docking study was performed to study their binding affinities in the VEGFR-2 active site and sorafenib was used as a reference VEGFR-2 inhibitor. Additionally, VEGFR-2 enzyme inhibitory evaluation was performed on compounds exhibiting remarkable anticancer activity and good binding affinity in the active site of the enzyme.