Abstract
BackgroundBiotransformation is an effective technique for the synthesis of libraries of bioactive compounds. Current study on microbial transformation of dihydrotestosterone (DHT) (1) was carried out to produce various functionalized metabolites.ResultsMicrobial transformation of DHT (1) by using two fungal cultures resulted in potent butyrylcholinesterase (BChE) inhibitors. Biotransformation with Macrophomina phaseolina led to the formation of two known products, 5α-androstan-3β,17β-diol (2), and 5β-androstan-3α,17β-diol (3), while biotransformation with Gibberella fujikuroi yielded six known metabolites, 11α,17β-dihydroxyandrost-4-en-3-one (4), androst-1,4-dien-3,17-dione (5), 11α-hydroxyandrost-4-en-3,17-dione (6), 11α-hydroxyandrost-1,4-dien-3,17-dione (7), 12β-hydroxyandrost-1,4-dien-3,17-dione (8), and 16α-hydroxyandrost-1,4-dien-3,17-dione (9). Metabolites 2 and 3 were found to be inactive, while metabolite 4 only weakly inhibited the enzyme. Metabolites 5–7 were identified as significant inhibitors of BChE. Furthermore, predicted results from docking simulation studies were in complete agreement with experimental data. Theoretical results were found to be helpful in explaining the possible mode of action of these newly discovered potent BChE inhibitors. Compounds 8 and 9 were not evaluated for enzyme inhibition activity both in vitro and in silico, due to lack of sufficient quantities.ConclusionBiotransformation of DHT (1) with two fungal cultures produced eight known metabolites. Metabolites 5–7 effectively inhibited the BChE activity. Cholinesterase inhibition is among the key strategies in the management of Alzheimer’s disease (AD). The experimental findings were further validated by in silico inhibition studies and possible modes of action were deduced.
Highlights
Biotransformation is an effective technique for the synthesis of libraries of bioactive compounds
In continuation of our recent work on the microbial transformation of important steroids [2], we investigated the microbial biotransformation of DHT
The 13C-NMR spectrum had two hydroxyl-bearing. This is the first report of microbial transformation of DHT (1) (Figure 1), (C19H30O2) with M. phaseolina and G. fujikuroi
Summary
Biotransformation is an effective technique for the synthesis of libraries of bioactive compounds. Current study on microbial transformation of dihydrotestosterone (DHT) (1) was carried out to produce various functionalized metabolites. In continuation of our recent work on the microbial transformation of important steroids [2], we investigated the microbial biotransformation of DHT. The rationale was DHT (1) Figure 1, plays a vital role in the growth and differentiation of ventral prostate. Due to its weaker interaction with the androgen receptor as compared to testosterone, DHT has a stronger androgenic potency [4]. It plays a vital role in human hair loss [5]
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