Biotransformation of anabolic compound methasterone with Macrophomina phaseolina, Cunninghamella blakesleeana, and Fusarium lini, and TNF-α inhibitory effect of transformed products

Steroids. 2017 Dec;128:75-84. doi: 10.1016/j.steroids.2017.04.001. Epub 2017 Apr 9.


Microbial transformation of methasterone (1) was investigated with Macrophomina phaseolina, Cunninghamella blakesleeana, and Fusarium lini. Biotransformation of 1 with M. phaseolina yielded metabolite 2, while metabolites 3-7 were obtained from the incubation of 1 with C. blakesleeana. Metabolites 8-13 were obtained through biotransformation with F. lini. All metabolites, except 13, were found to be new. Methasterone (1) and its metabolites 2-6, 9, 10, and 13 were then evaluated for their immunomodulatory effects against TNF-α, NO, and ROS production. Among all tested compounds, metabolite 6 showed a potent inhibition of proinflammatory cytokine TNF-α (IC50=8.1±0.9μg/mL), as compared to pentoxifylline used as a standard (IC50=94.8±2.1μg/mL). All metabolites were also evaluated for the inhibition of NO production at concentration of 25μg/mL. Metabolites 6 (86.7±2.3%) and 13 (62.5±1.5%) were found to be the most potent inhibitors of NO as compared to the standard NG-monomethyl-l-arginine acetate (65.6±1.1%). All metabolites were found to be non-toxic against PC3, HeLa, and 3T3 cell lines. Observed inhibitory potential of metabolites 6 and 13 against pro-inflammatory cytokine TNF-α, as well as NO production makes them interesting leads for further studies.

Keywords: Anabolic-androgenic; Biotransformation; Cunninghamella blakesleeana; Fusarium lini; Macrophomina phaseolina; Methasterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Ascomycota / genetics
  • Biotransformation*
  • Cell Proliferation / drug effects
  • Cunninghamella / genetics
  • Fusarium / genetics
  • HeLa Cells
  • Humans
  • Mice
  • Nitric Oxide / metabolism
  • Reactive Oxygen Species / metabolism
  • Testosterone Congeners / biosynthesis*
  • Testosterone Congeners / chemistry
  • Testosterone Congeners / metabolism
  • Testosterone Congeners / pharmacology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism


  • Reactive Oxygen Species
  • Testosterone Congeners
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide