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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 μM. The prominent compound with remarkable activity (GI50 = 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-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.

The emergence of staphylococcal canine pathogens resistant to multiple antimicrobial agents is a growing and urgent problem in veterinary practice. Antimicrobial peptides (AMPs) seem to be a promising alternative to conventional antibiotics. The aim of this in vitro study was to evaluate the antimicrobial activity of selected AMPs against pathogenic staphylococcal strains, including multidrug- and methicillin-resistant strains isolated from canine pyoderma cases. Seven antimicrobial peptides (aurein 1.2, CAMEL, citropin 1.1, protegrin-1, pexiganan, temporin A and uperin 3.6) synthesized by the 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase method were tested. The minimal inhibitory and minimal bactericidal concentrations (MIC and MBC) were determined by the broth microdilution method. The study showed that analyzed AMPs exerted an extensive effect against canine pathogens, with the most active peptide being uperin 3.6. The tested AMPs were equally efficient against both resistant- and susceptible staphylococcal strains and were more efficient against Staphylococcus pseudintermedius than against Staphylococcus aureus strains. Our findings are particularly interesting from a clinical perspective, as they point to AMPs as potential therapeutic topical agents in canine pyoderma cases associated with antimicrobial resistance of staphylococci.