Microbial biotransformation of beclomethasone dipropionate by Aspergillus niger

In the present research, the steroidal anti-asthmatic drug beclomethasone dipropionate was subjected to microbial biotransformation by Aspergillus niger. Beclomethasone dipropionate was transformed into various metabolites first time from microbial transformation. New drug metabolites produced can act as new potential drug molecules and can replace the old drugs in terms of safety, efficacy, and least resistance. They were purified by preparative thin layer chromatography technique, and their structures were elucidated using modern spectroscopic techniques, such as 13C NMR, 1H NMR, HMQC, HMQC, COSY, and NOESY, and mass spectrometry, such as EI-MS. Four metabolites were purified: (i) beclomethasone 17-monopropionate, (ii) beclomethasone 21-monopropionate, (iii) beclomethasone, and (iv) 9beta,11beta-epoxy-17,21-dihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 21-propionate.

本研究以甾体类抗哮喘药物二丙酸倍氯米松（beclomethasone dipropionate）为底物，采用黑曲霉（Aspergillus niger）对其开展微生物生物转化实验。本研究首次通过微生物转化途径，将二丙酸倍氯米松转化为多种代谢产物。所获得的新型药物代谢产物可作为潜在候选药物分子，在安全性、有效性及最低耐药性方面有望替代传统药物。研究采用制备型薄层色谱（preparative thin layer chromatography）技术对代谢产物进行分离纯化，并通过现代波谱技术（包括13C核磁共振波谱（13C NMR）、1H核磁共振波谱（1H NMR）、异核多量子相干谱（HMQC）、HMQC、相关谱（COSY）以及核Overhauser效应谱（NOESY））与质谱技术（如电子轰击质谱（EI-MS））解析其化学结构。最终共纯化得到4种代谢产物：(i) 17-单丙酸倍氯米松（beclomethasone 17-monopropionate），(ii) 21-单丙酸倍氯米松（beclomethasone 21-monopropionate），(iii) 倍氯米松（beclomethasone），(iv) 9β,11β-环氧-17,21-二羟基-16β-甲基孕甾-1,4-二烯-3,20-二酮-21-丙酸酯（9beta,11beta-epoxy-17,21-dihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 21-propionate）。