Gram-scale synthesis, in silico analysis, and antimicrobial potential of phytoalexins camalexin, N-methylcamalexin, including their novel methylated analogues

N-methylcamalexin (5a) and its novel methylated analogues were synthesised using a convenient two-step approach involving a multicomponent α-amidoalkylation reaction followed by oxidative rearomatization. In this way, phytoalexin N-methylcamalexin was obtained in 1.014 g with a high yield (86%). The structure of the synthesised compounds was characterised spectrally using 1H-,13C{1H}-, HSQC-NMR, FTIR, and HRMS data. The conducted in silico analysis predicted the absence of general cyto- and nutritional toxicity for phytoalexins (5a), (6) and analogues (5b), (5c). Thus, the antimicrobial activity of these molecules was evaluated. N-methylcamalexin demonstrated the highest activity among the tested compounds against saprophytic microorganisms, with a minimum inhibitory concentration MIC – 0.140 µmol. The compound 4-methyl-N-methylcamalexin (5b) showed high antibacterial potential against Bacillus cereus ATCC 14579 with MIC – 0.131 µmol. The highest antimicrobial activity against the tested microorganisms was observed for Camalexin (6), with the lowest MIC – 0.009 µmol against Aspergillus niger ATCC 9029.