Sultana Nighat
Pharmaceutical Research Center, PCSIR Laboratories Complex, Shahrah-e-Dr. Salimuzzaman Siddiqui, Off University Road, Karachi 75280, Pakistan.
Steroids. 2018 Aug;136:76-92. doi: 10.1016/j.steroids.2018.01.007. Epub 2018 Jan 31.
Steroids are perhaps one of the most widely used group of drugs in present day. Beside the established utilization as immunosuppressive, anti-inflammatory, anti-rheumatic, progestational, diuretic, sedative, anabolic and contraceptive agents, recent applications of steroid compounds include the treatment of some forms of cancer, osteoporosis, HIV infections and treatment of declared AIDS. Steroids isolated are often available in minute amounts. So biotransformation of natural products provides a powerful means in solving supply problems in clinical trials and marketing of the drug for obtaining natural products in bulk amounts. If the structure is complex, it is often an impossible task to isolate enough of the natural products for clinical trials. The microbial biotransformation of steroids yielded several novel metabolites, exhibiting different activities. The metabolites produced from pregnenolone acetate by Cunning hamella elegans and Rhizopus stolonifer were screened against tyrosinase and cholinesterase showed significant inhibitory activities than the parent compound. Diosgenin and its transformed sarsasapogenin were screened for their acetyl cholinesterase and butyryl cholinesterase inhibitory activities. Sarsasapogenin was screened for phytotoxicity, and was found to be more active than the parent compound. Diosgenin, prednisone and their derivatives were screened for their anti-leishmanial activity. All derivatives were found to be more active than the parent compound. The biotransformation of steroids have been reviewed to a little extent. This review focuses on the biotransformation and functions of selected steroids, the classification, advantages and agents of enzymatic biotransformation and examines the potential role of new enzymatically transformed steroids and their derivatives in the chemoprevention and treatment of other diseases. tyrosinase and cholinesterase inhibitory activities, severe asthma, rheumatic disorders, renal disorders and diseases of inflammatory bowel, skin, gastrointestinal tract.
类固醇可能是当今使用最广泛的一类药物。除了既定的作为免疫抑制剂、抗炎药、抗风湿药、孕激素、利尿剂、镇静剂、同化激素和避孕药的用途外，类固醇化合物最近的应用还包括治疗某些形式的癌症、骨质疏松症、艾滋病毒感染以及已确诊的艾滋病。分离得到的类固醇通常含量极少。因此，天然产物的生物转化为解决临床试验中的供应问题以及药物上市以大量获取天然产物提供了一种有力手段。如果结构复杂，分离出足够用于临床试验的天然产物往往是一项不可能完成的任务。类固醇的微生物生物转化产生了几种具有不同活性的新代谢产物。筛选了由雅致小克银汉霉和匍枝根霉对醋酸孕烯醇酮进行生物转化产生的代谢产物对酪氨酸酶和胆碱酯酶的抑制活性，结果显示其比母体化合物具有更强的抑制活性。筛选了薯蓣皂苷元及其转化产物菝葜皂苷元对乙酰胆碱酯酶和丁酰胆碱酯酶的抑制活性。筛选了菝葜皂苷元的植物毒性，发现其比母体化合物更具活性。筛选了薯蓣皂苷元、泼尼松及其衍生物的抗利什曼原虫活性。发现所有衍生物的活性均比母体化合物更强。对类固醇的生物转化已有一定程度的综述。本综述重点关注选定类固醇的生物转化和功能、酶促生物转化的分类、优势和试剂，并探讨新的酶促转化类固醇及其衍生物在化学预防和治疗其他疾病中的潜在作用，如酪氨酸酶和胆碱酯酶抑制活性、重度哮喘、风湿性疾病、肾脏疾病以及炎症性肠病、皮肤病、胃肠道疾病。
