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

Abstract

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 and antimicrobial agents. The structures of the prepared compounds were evaluated based on elemental analysis, IR, 1H- and 13NMR, as well as MS spectra. X-ray crystal analysis of the representative 2-(1H-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 GI50 values of all tests in the range of 0.38-7.91 mM. The prominent compound with remarkable activity (GI50 = 0.0244-5.06 mM) and high potency (TGI = 0.0866-0.938 mM) 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-1H-indol-2-yl)acrylonitrile (5c). Moreover, the selected 2-(1H-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-(1H-indol-2-yl)-3-(1H-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.

In Vitro and In Silico Evaluation of Antiproliferative Activity of New Isoxazolidine Derivatives Targeting EGFR: Design, Synthesis, Cell Cycle Analysis, and Apoptotic Inducers

“…As a result, the trend of the RGyr plot versus simulation time and its low fluctuation surely explain the residual backbone and how folding of the EGFR protein remained stable after interaction with compounds 2f and 2g. [35][36][37][38][39][40][41] An in silico study (Table 4) of the most biologically active synthesized compounds 2f and 2g has been assessed by Swiss ADME server. Lipinski's rule states that both investigated molecules satisfied this rule and thereby should be taken orally.…”

“…Our findings revealed that 2f and 2g could be good templates for further drug discovery and development. [35][36][37][38][39][40][41] An in silico study (Table 4) of the most biologically active synthesized compounds 2f and 2g has been assessed by Swiss ADME server. Lipinski's rule states that both investigated molecules satisfied this rule and thereby should be taken orally.…”

Synthesis and anti-infective potency study of a Ru-based complex bearing benzonitrile against Staphylococcus aureus

“…22–24 It is reported that nitrile group modified complexes show good antibacterial activity against Gram-positive and Gram-negative bacteria. 25–27 Importantly, the nitrile group can be used as bioactive “warheads” to hydrogen bond with proteins. 28 The nitrile group has significant effects on bacterial communities due to its conjugation effects.…”