Khan Saifullah, Halim Sobia Ahsan, Kashif Muhammad, Jabeen Almas, Asif Muhmammad, Mesaik Muhammad Ahmed, Ul-Haq Zaheer, Dar Ahsana, Choudhary Muhammad Iqbal
Department of Biotechnology, Faculty of Science, University of Karachi, Karachi 75270, Pakistan.
Department of Chemistry, Federal Urdu University for Arts, Science & Technology, Gulshan-e-Iqbal Campus, Karachi 75300, Pakistan.
Chem Cent J. 2013 Oct 7;7:163. doi: 10.1186/1752-153X-7-163. eCollection 2013.
Plant Biotransformation is one of the tools for structural modifications of the organic substrate of low, moderate or high biological value utilizing plant cultured cells, these modifications of organic structures may lead to biologically augmented products and which may be ultimately substantial in cure or improvement of various morbidities and diseases.
Azadirachta indica A. Juss. suspension culture was employed for the biotransformation of dianabol (1) for the first time, and two metabolites, 17β-hydroxy-17α-methyl-5α-androst-1-en-3-one (2), and 17β-hydroxy-17α-methyl-5α-androstan-3-one (3) were obtained.
Most important aspect of this work was the evaluation of metabolite 2, which strongly and differentially suppressed [not affecting whole blood and human polymorphonuclear cells (PMN)] the phytohemagglutinin (PHA)-activated T-cell proliferation (IC50: <10.33 μM), and also found to inhibit IL-2 production (IC50: 16.89 ± 1.32) unlike metabolite 3 and compound 1. Compound 2 also exhibited anticancer activity against lung cancer cell line; NCI-H460, it moderately inhibited the growth of cancer cells (22.5 ± 4.15 μM). Furthermore, a good correlation between the predicted binding energies of the compounds acquired by the FlexX program and the experimental affinities were speculated upon interacting with IL-2 protein during molecular docking studies.
植物生物转化是利用植物培养细胞对低、中或高生物价值的有机底物进行结构修饰的工具之一，这些有机结构的修饰可能会产生生物增强产物，最终可能对各种疾病的治疗或改善具有重要意义。
首次利用印楝悬浮培养对大力补（1）进行生物转化，得到了两种代谢产物，17β-羟基-17α-甲基-5α-雄甾-1-烯-3-酮（2）和17β-羟基-17α-甲基-5α-雄甾烷-3-酮（3）。
这项工作最重要的方面是对代谢产物2的评估，其强烈且有差异地抑制[不影响全血和人多形核细胞（PMN）]植物血凝素（PHA）激活的T细胞增殖（IC50：<10.33 μM），并且还发现其抑制IL-2的产生（IC50：16.89±1.32），这与代谢产物3和化合物1不同。化合物2对肺癌细胞系NCI-H460也表现出抗癌活性，它适度抑制癌细胞的生长（22.5±4.15 μM）。此外，推测在分子对接研究中，FlexX程序获得的化合物预测结合能与实验亲和力之间存在良好的相关性，这些化合物与IL-2蛋白相互作用。
