Research Unit of Microbiology and Antimicrobial Substances, Department of Biochemistry, University of Dschang, P.O. Box 67, Dschang, Cameroon; Research Unit of Metabolic and Infectious Diseases, Department of Biomedical Sciences, Faculty of Science, University of Ngaoundéré, P.O. Box 454, Ngaoundéré, Cameroon; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Department of Chemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Steroids. 2020 Oct;162:108679. doi: 10.1016/j.steroids.2020.108679. Epub 2020 Jun 20.
Although the discovery of antibiotics has decreased the spread and severity of infectious diseases, their uncontrolled use has lead to the emergence of bacterial resistance to existing chemotherapeutic agents. Bacterial disease thus remains a challenge for health authorities in worldwide and especially in sub-Saharan Africa. Despite their efficacy, the miss-use of medicinal plants for the treatment of infectious diseases couple to the farming and hunting activities has contribute enormously to the destruction of many medicinal plant species. In search of an alternative for new and effective agents against bacterial infection, norandrostenedion (19-nor-4-androsten-3,17-dione) (1), was biotransformed by Cunninghamella blakesleeana ATCC 8688A and yielded a new metabolite, 6α,10 β -dihydroxy-19-nor-4-androsten-3-one (2), together with three known compounds, 10 β -hydroxy-19-nor-4-androsten-3,17-dione (3), 6 β,10 β,17 β -trihydroxy-19-nor-4-androsten-3-one (4) and 10 β,17 β -dihydroxy-19-nor-4-androsten-3-one (5). Their structures were elucidated on the basis ofspectroscopic techniques: NMR analysis (1D and 2D) and HRIE-MS and by comparison with previously reported data. In addition, the agar diffusion method was used to evaluate the diameter of the inhibition zone and INT colorimetric assay for MIC values. All metabolites obtained showed a potent and varied activity against tested bacteria. These results support the uses of biotransformation to develop new antimicrobial compounds for clinical application.
虽然抗生素的发现降低了传染病的传播和严重程度，但它们的滥用导致了细菌对现有化疗药物的耐药性的出现。细菌疾病仍然是全球卫生当局的一个挑战，尤其是在撒哈拉以南非洲。尽管药用植物具有疗效，但由于其被滥用于治疗传染病，加上农业和狩猎活动，许多药用植物物种已遭到严重破坏。为了寻找对抗细菌感染的新的有效药物，对诺孕烯（19-去甲-4-雄烯-3,17-二酮）（1）进行了 Cunninghamella blakesleeana ATCC 8688A 的生物转化，得到了一个新的代谢产物 6α,10β-二羟基-19-去甲-4-雄烯-3-酮（2），以及三种已知化合物：10β-羟基-19-去甲-4-雄烯-3,17-二酮（3）、6β,10β,17β-三羟基-19-去甲-4-雄烯-3-酮（4）和 10β,17β-二羟基-19-去甲-4-雄烯-3-酮（5）。根据光谱技术：NMR 分析（1D 和 2D）和高分辨电喷雾电离质谱（HRIE-MS）以及与先前报道的数据进行比较，确定了它们的结构。此外，还使用琼脂扩散法评估了抑制区的直径和 INT 比色法测定 MIC 值。所有获得的代谢产物对测试的细菌均表现出强大而多样的活性。这些结果支持利用生物转化来开发新的用于临床应用的抗菌化合物。
