Microbial transformation of nandrolone with Cunninghamella echinulata and Cunninghamella blakesleeana and evaluation of leishmaniacidal activity of transformed products

Abstract

Therapeutic potential of nandrolone and its derivatives against leishmaniasis has been studied. A number of derivatives of nandrolone (1) were synthesized through biotransformation. Microbial transformation of nandrolone (1) with Cunninghamella echinulata and Cunninghamella blakesleeana yielded three new metabolites, 10β,12β,17β-trihydroxy-19-nor-4-androsten-3-one (2), 10β,16α,17β-trihydroxy-19-nor-4-androsten-3-one (3), and 6β,10β,17β-trihydroxy-19-nor-4-androsten-3-one (4), along with four known metabolites, 10β,17β-dihydroxy-19-nor-4-androsten-3-one (5), 6β,17β-dihydroxy-19-nor-4-androsten-3-one (6) 10β-hydroxy-19-nor-4-androsten-3,17-dione (7) and 16β,17β- dihydroxy-19-nor-4-androsten-3-one (8). Compounds 1-8 were evaluated for their anti-leishmanial activity. Compounds 1 and 8 showed a significant activity in vitro against Leishmania major. The leishmanicidal potential of compounds 1-8 (IC50 = 32.0 ± 0.5, >100, 77.39 ± 5.52, 70.90 ± 1.16, 54.94 ± 1.01, 80.23 ± 3.39, 61.12 ± 1.39 and 29.55 ± 1.14 μM, respectively) can form the basis for the development of effective therapies against the protozoal tropical disease leishmaniasis. © 2014 Elsevier Inc. All rights reserved.