Antimicrobial activity of o-carboranylalanine

Functionalized polyhedral carboranes, including amino acid analogs, have unique physicochemical properties and are used as experimental anticancer agents. However, our current knowledge on their effect in nonmammalian biological systems is limited. We investigated the activity spectrum in vitro of o-carboranylalanine (o-Cba), considered to be a highly lipophilic analog of phenylalanine, against representative plant pathogenic bacteria and fungi of various taxonomic position. The antibacterial effect of o-Cba against some species was comparable to that of the widely used agricultural antibiotic, streptomycin. The sensitivity of individual bacterial species to o-Cba within the same genus varied to a greater extent than the average sensitivity of various genera. In general, this carborane-containing amino acid was more toxic to Gram positive bacteria (Bacillus, Corynebacterium, Curtobacterium, Micrococcus, Rhodococcus, and Staphylococcus) than to Gram negative ones (Agrobacterium, Erwinia, Escherichia, Pseudomonas, Rhizobium, and Xanthomonas). Compared to the commercial fungicide, prochloraz, o-Cba was weakly toxic against various fungi (Zygo- and Ascomycota). It was also inferior to the commercial fungicide metalaxyl in inhibiting the vegetative growth of oomyceteous plant pathogens (Pythium irregulare, Phytophthora cryptogea and Plasmopara halstedii). Against the asexual spores of P. halstedii, o-Cba, however, was over a thousandfold more active than tridemorph, a selective zoospore inhibitor fungicide. For all taxonomic groups, the observed antimicrobial effect of o-Cba could be diminished with histidine, but not with phenylalanine. In studies on healthy and mildew-infected sunflower and tobacco plants o-Cba showed neither fungicidal nor phytotoxic effects at 500 ppm. This is the first report on the biological activity spectrum of a carborane-containing amino acid.