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

A series of 2-(1H-indol-2-yl)-3-acrylonitrile derivatives, 2a–x, 3, 4a–b, 5a–d, 6a–b, and 7, were synthesized as potential antitumor antimicrobial agents. The structures the prepared compounds evaluated based on elemental analysis, IR, 1H- 13NMR, well MS spectra. X-ray crystal analysis representative 2l showed that acrylonitrile double bond was Z-configured. All screened at National Cancer Institute (USA) for their activities against a panel approximately 60 human tumor cell lines relationship between structure in vitro activity is discussed. Compounds interest 5a–d significant growth inhibition potency various with mean midpoint GI50 values all tests range 0.38–7.91 μM. prominent compound remarkable (GI50 = 0.0244–5.06 μM) high (TGI 0.0866–0.938 some leukemia (HL-60(TB)), non-small lung cancer (NCI-H522), colon (COLO 205), CNS (SF-539, SNB-75), ovarian ((OVCAR-3), renal (A498, RXF 393), breast (MDA-MB-468) 3-[4-(dimethylamino)phenyl]-2-(1-methyl-1H-indol-2-yl)acrylonitrile (5c). Moreover, selected 2-(1H-indol-2-yl)-3-acrylonitriles 2a–c 2e–x antibacterial antifungal Gram-positive Gram-negative pathogens Candida albicans. Among them, 2-(1H-indol-2-yl)-3-(1H-pyrrol-2-yl)acrylonitrile (2x) most potent therefore it can be considered lead further development Finally, molecular docking studies drug-likeness ADME profile prediction carried out.