Indole-Acrylonitrile Derivatives as Potential Antitumor and Antimicrobial Agents-Synthesis, In Vitro and In Silico Studies.

A series of 2-(1 H -indol-2-yl)-3-acrylonitrile derivatives, 2a - x , 3 , 4a - b , 5a - d , 6a - b , and 7 , were synthesized as potential antitumor and antimicrobial agents. The structures of the prepared compounds were evaluated based on elemental analysis, IR, 1 H- and 13 NMR, as well as MS spectra. X-ray crystal analysis of the representative 2-(1 H -indol-2-yl)-3-acrylonitrile 2l showed that the acrylonitrile double bond was Z -configured. All compounds were screened at the National Cancer Institute (USA) for their activities against a panel of approximately 60 human tumor cell lines and the relationship between structure and in vitro antitumor activity is discussed. Compounds of interest 2l and 5a - d showed significant growth inhibition potency against various tumor cell lines with the mean midpoint GI 50 values of all tests in the range of 0.38-7.91 μM. The prominent compound with remarkable activity (GI 50 = 0.0244-5.06 μM) and high potency (TGI = 0.0866-0.938 μM) against some cell lines of leukemia (HL-60(TB)), non-small cell lung cancer (NCI-H522), colon cancer (COLO 205), CNS cancer (SF-539, SNB-75), ovarian cancer ((OVCAR-3), renal cancer (A498, RXF 393), and breast cancer (MDA-MB-468) was 3-[4-(dimethylamino)phenyl]-2-(1-methyl-1 H -indol-2-yl)acrylonitrile ( 5c ). Moreover, the selected 2-(1 H -indol-2-yl)-3-acrylonitriles 2a - c and 2e - x were evaluated for their antibacterial and antifungal activities against Gram-positive and Gram-negative pathogens as well as Candida albicans . Among them, 2-(1 H -indol-2-yl)-3-(1 H -pyrrol-2-yl)acrylonitrile ( 2x ) showed the most potent antimicrobial activity and therefore it can be considered as a lead structure for further development of antimicrobial agents. Finally, molecular docking studies as well as drug-likeness and ADME profile prediction were carried out.