Synthesis, DNA affinity, and antimicrobial activity of 4-substituted phenyl-2,2′-bichalcophenes and aza-analogues

A series of bichalcophene monoamidines 4a–f were synthesized from the corresponding mononitriles 3a–f via a direct reaction with LiN(TMS)2 followed by deprotection with ethanolic HCl (gas). Bichalcophene mononitriles 3a–f were synthesized via palladium-catalyzed coupling reactions. Thus, a Stille coupling reaction was performed to prepare 6-[5-(thiophen-2-yl)furan-2-yl]nicotinonitrile (3e), when 6-(5-bromofuran-2-yl)nicotinonitrile was allowed to react with 2-n-tributyltin thiophene. The tested bichalcophenes showed a wide range of DNA and protein degradation effect as judged from agarose gel and SDS-PAGE, respectively. Bichalcophenes 3a–f and 4a–f have broad-spectrum antibacterial efficacy being highly active against both Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa, and Escherichia coli) bacterial strains. The antifungal activity of these bichalcophene series against Saccharomyces cerevisiae was demonstrated. The MIC of bichalcophenes 3a–f and 4a–f against various microorganisms was also determined. The tested bichalcophenes mimic SOD like activity and inhibited the superoxide radical generation.