Pedras M Soledade C, Jha Mukund
Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon, Canada SK S7N 5C9.
Bioorg Med Chem. 2006 Jul 15;14(14):4958-79. doi: 10.1016/j.bmc.2006.03.014. Epub 2006 Apr 17.
Brassinin (1), a crucial plant defense produced by crucifers, is detoxified by the phytopathogenic fungus Leptosphaeria maculans (Phoma lingam) to indole-3-carboxaldehyde using a putative brassinin oxidase. Potential inhibitors of brassinin detoxification were designed by replacement of its dithiocarbamate group (toxophore) with carbamate, dithiocarbonate, urea, thiourea, sulfamide, sulfonamide, dithiocarbazate, amide, and ester functional groups. In addition, the indolyl moiety was substituted for naphthalenyl and phenyl. The syntheses and chemical characterization of these potential detoxification inhibitors, along with their antifungal and cytotoxic activity, as well as screening using cultures of L. maculans are reported. Overall, three types of interaction were observed in cultures of L. maculans co-incubated with the potential inhibitors and brassinin: (1) a decrease on the rate of brassinin detoxification due to the strong inhibitory activity of the compound on fungal growth, (2) a decrease on the rate of brassinin detoxification due to the inhibitory activity of the compound on the putative brassinin oxidase, and (3) a low to no detectable effect on the rate of brassinin detoxification. A noticeable decrease in the rate of brassinin detoxification was observed in the presence of N'-methylbrassinin, methyl N-methyl-N-(naphthalen-2-ylmethyl) dithiocarbamate, tryptophol dithiocarbonate, and methyl 3-phenyldithiocarbazate. Tryptophol dithiocarbonate appeared to be the best inhibitor among the designed compounds, representing the first inhibitor of brassinin detoxification and potentially the first selective protecting agent of oilseed crucifers against L. maculans infestation.
油菜素（1）是十字花科植物产生的一种关键植物防御物质，植物致病真菌大斑壳单隔孢菌（十字花科茎点霉）利用一种假定的油菜素氧化酶将其解毒为吲哚 - 3 - 甲醛。通过用氨基甲酸酯、二硫代碳酸酯、脲、硫脲、磺胺、磺酰胺、二硫代氨基甲酸盐、酰胺和酯官能团取代其二硫代氨基甲酸盐基团（毒基），设计了油菜素解毒的潜在抑制剂。此外，吲哚基部分被萘基和苯基取代。报道了这些潜在解毒抑制剂的合成、化学表征及其抗真菌和细胞毒性活性，以及使用大斑壳单隔孢菌培养物进行的筛选。总体而言，在与潜在抑制剂和油菜素共同孵育的大斑壳单隔孢菌培养物中观察到三种相互作用类型：（1）由于化合物对真菌生长的强抑制活性，油菜素解毒速率降低；（2）由于化合物对假定的油菜素氧化酶的抑制活性，油菜素解毒速率降低；（3）对油菜素解毒速率的影响低至无法检测。在存在N'-甲基油菜素、甲基N - 甲基 - N -（萘 - 2 - 基甲基）二硫代氨基甲酸盐、色醇二硫代碳酸酯和甲基3 - 苯基二硫代氨基甲酸盐的情况下，观察到油菜素解毒速率显著降低。色醇二硫代碳酸酯似乎是所设计化合物中最好的抑制剂，代表了油菜素解毒的第一种抑制剂，并且可能是油菜籽十字花科植物对抗大斑壳单隔孢菌侵染的第一种选择性保护剂。
