Baydoun Elias, Karam Martin, Khan Mahwish Shafi Ahmed, Ahmad Malik Shoaib, Smith Colin, Abdel-Massih Roula, Choudhary M Iqbal
Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon.
Department of Biology, American University of Beirut, Beirut 1107 2020, Lebanon.
Steroids. 2014 Oct;88:95-100. doi: 10.1016/j.steroids.2014.06.020. Epub 2014 Jul 8.
Therapeutic potential of nandrolone and its derivatives against leishmaniasis has been studied. A number of derivatives of nandrolone (1) were synthesized through biotransformation. Microbial transformation of nandrolone (1) with Cunninghamella echinulata and Cunninghamella blakesleeana yielded three new metabolites, 10β,12β,17β-trihydroxy-19-nor-4-androsten-3-one (2), 10β,16α,17β-trihydroxy-19-nor-4-androsten-3-one (3), and 6β,10β,17β-trihydroxy-19-nor-4-androsten-3-one (4), along with four known metabolites, 10β,17β-dihydroxy-19-nor-4-androsten-3-one (5), 6β,17β-dihydroxy-19-nor-4-androsten-3-one (6) 10β-hydroxy-19-nor-4-androsten-3,17-dione (7) and 16β,17β-dihydroxy-19-nor-4-androsten-3-one (8). Compounds 1-8 were evaluated for their anti-leishmanial activity. Compounds 1 and 8 showed a significant activity in vitro against Leishmania major. The leishmanicidal potential of compounds 1-8 (IC50=32.0±0.5, >100, 77.39±5.52, 70.90±1.16, 54.94±1.01, 80.23±3.39, 61.12±1.39 and 29.55±1.14 μM, respectively) can form the basis for the development of effective therapies against the protozoal tropical disease leishmaniasis.
已对诺龙及其衍生物治疗利什曼病的潜力进行了研究。通过生物转化合成了多种诺龙（1）的衍生物。用刺孢小克银汉霉和布氏小克银汉霉对诺龙（1）进行微生物转化，产生了三种新的代谢产物，10β,12β,17β-三羟基-19-去甲-4-雄烯-3-酮（2）、10β,16α,17β-三羟基-19-去甲-4-雄烯-3-酮（3）和6β,10β,17β-三羟基-19-去甲-4-雄烯-3-酮（4），以及四种已知的代谢产物，10β,17β-二羟基-19-去甲-4-雄烯-3-酮（5）、6β,17β-二羟基-19-去甲-4-雄烯-3-酮（6）、10β-羟基-19-去甲-4-雄烯-3,17-二酮（7）和16β,17β-二羟基-19-去甲-4-雄烯-3-酮（8）。对化合物1-8的抗利什曼活性进行了评估。化合物1和8在体外对硕大利什曼原虫显示出显著活性。化合物1-8的杀利什曼潜力（IC50分别为32.0±0.5、>100、77.39±5.52、70.90±1.16、54.94±1.01、80.23±3.39、61.12±1.39和29.55±1.14μM）可为开发针对原生动物热带疾病利什曼病的有效疗法奠定基础。
