Department of Integrative Biology, School of Bio sciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India.
BogaR Laboratories, Peddapuram, 533437, Andhra Pradesh, India.
Toxicon. 2019 Dec;170:60-67. doi: 10.1016/j.toxicon.2019.09.018. Epub 2019 Sep 18.
Aflatoxins are mutagenic secondary metabolites produced by certain ubiquitous saprophytic fungi. These contaminate agricultural crops and pose a serious health threat to humans and livestock all over the world. Benzimidazole and its derivatives are biologically active heterocyclic compounds known for their fungicidal activity. In the present study, second and sixth position substituted benzimidazole derivatives are tested for their antifungal and anti-aflatoxigenic activity. Aflatoxigenic strain of Aspergillus flavus cultured in Yeast extract sucrose (YES) medium as well as in rice in the presence and absence of test compounds. 2-(2-Furyl) benzimidazole (FBD) showed complete inhibition of fungal growth at 50 μg/mL. However, the polar derivatives of FBD viz. 6-NFBD, 6-AFBD, 6-CAFBD, and 6-CFBD did not impair the fungal growth but effectively inhibited aflatoxin B biosynthesis. Significant down-regulation of aflR gene involved in regulation and aflB structural gene for aflatoxin B biosynthesis was observed in presence of 6-NFBD. These benzimidazole derivatives also showed good anti-aflatoxigenic activity in rice, though the IC concentrations in rice were comparatively higher than those in YES medium. This study summarizes the most notable structure-activity relationship (SAR) of 2-(2-Furyl) benzimidazoles for anti-aflatoxigenic and anti-fungal activities. These molecules can be further studied for their applications in industrial fermentation processes vulnerable to mold growth and subsequent aflatoxin B synthesis like koji fermentation, cheese production, etc.
黄曲霉毒素是某些普遍存在的腐生真菌产生的致突变次级代谢物。这些毒素污染了农作物，对全世界的人类和牲畜的健康构成了严重威胁。苯并咪唑及其衍生物是具有杀菌活性的生物活性杂环化合物。在本研究中，测试了苯并咪唑的第二和第六位取代衍生物的抗真菌和抗黄曲霉毒素活性。在酵母提取物蔗糖（YES）培养基中以及在存在和不存在测试化合物的情况下，培养黄曲霉属的产黄曲霉毒素菌株。2-（2-呋喃基）苯并咪唑（FBD）在 50μg/mL 时完全抑制真菌生长。然而，FBD 的极性衍生物，即 6-NFBD、6-AFBD、6-CAFBD 和 6-CFBD，并没有损害真菌的生长，但有效地抑制了黄曲霉毒素 B 的生物合成。在存在 6-NFBD 的情况下，观察到参与调节和黄曲霉毒素 B 生物合成的 aflR 基因的显著下调。这些苯并咪唑衍生物在大米中也表现出良好的抗黄曲霉毒素活性，尽管在大米中的 IC 浓度比在 YES 培养基中的要高。本研究总结了 2-（2-呋喃基）苯并咪唑在抗黄曲霉毒素和抗真菌活性方面最显著的构效关系（SAR）。这些分子可以进一步研究它们在工业发酵过程中的应用，这些过程容易受到霉菌生长和随后的黄曲霉毒素 B 合成的影响，如曲霉菌发酵、奶酪生产等。
