title: Microbial transformation of anti-cancer steroid exemestane and cytotoxicity of its metabolites against cancer cell lines.
abstract: BACKGROUND
  Microbial transformation of steroids has been extensively used for the synthesis of steroidal drugs, that often yield novel analogues, not easy to obtain by chemical synthesis. We report here fungal transformation of a synthetic steroidal drug, exemestane, used for the treatment of breast cancer and function through inhibition of aromatase enzyme.
  
  
  RESULTS
  Microbial transformation of anti-cancer steroid, exemestane (1), was investigated by using two filamentous fungi. Incubation of 1 with fungi Macrophomina phaseolina, and Fusarium lini afforded three new, 11α-hydroxy-6-methylene-androsta-1, 4-diene-3,17-dione (2), 16β, 17β-dihydroxy-6-methylene-androsta-1, 4-diene-3-one (3), and 17β-hydroxy-6-methylene-androsta-1, 4-diene-3, 16-dione (4), and one known metabolites, 17β-hydroxy-6-methylene-androsta-1, 4-diene-3-one (5). Their structures were deduced spectroscopically. Compared to 1 (steroidal aromatase inactivator), the transformed metabolites were also evaluated for cytotoxic activity by using a cell viability assay against cancer cell lines (HeLa and PC3). Metabolite 2 was found to be moderately active against both the cell lines.
  
  
  CONCLUSIONS
  Biotransformation of exemestane (1) provides an efficient method for the synthesis of new analogues of 1. The metabolites were obtained as a result of reduction of double bond and hydroxylation. The transformed product 2 exhibited a moderate activity against cancer cell lines (HeLa and PC3). These transformed products can be studied for their potential as drug candidates.
authors.affiliation: American University of Beirut, Beirut, 1107 2020, Lebanon. eliasbay1@yahoo.com.
authors.forename: Elias
authors.initials: E
authors.lastname: Baydoun
authors.forename: Marium
authors.initials: M
authors.lastname: Bibi
authors.forename: Muhammad Asif
authors.initials: MA
authors.lastname: Iqbal
authors.forename: Atia-Tul
authors.initials: AT
authors.lastname: Wahab
authors.forename: Dina
authors.initials: D
authors.lastname: Farran
authors.forename: Colon
authors.initials: C
authors.lastname: Smith
authors.forename: Samina A
authors.initials: SA
authors.lastname: Sattar
authors.forename: Atta-Ur
authors.initials: AU
authors.lastname: Rahman
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
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