Cargando…

Structural transformation of methasterone with Cunninghamella blakesleeana and Macrophomina phaseolina

An anabolic-androgenic synthetic steroidal drug, methasterone (1) was transformed by two fungi, Cunninghamella blakesleeana and Macrophimina phaseclina. A total of six transformed products, 6β,7β,17β-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (2), 6β,7α,17β-trihydroxy-2α,17α-dimethyl-5α-androsta...

Descripción completa

Detalles Bibliográficos
Autores principales: Aamer, Muhammad, Siddiqui, Mahwish, Jabeen, Almas, Irshad, Rimsha, Khan, Farooq-Ahmad, Atia-tul-Wahab, Choudhary, M. Iqbal, Wang, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985176/
https://www.ncbi.nlm.nih.gov/pubmed/35424863
http://dx.doi.org/10.1039/d2ra01396g
_version_ 1784682316969279488
author Aamer, Muhammad
Siddiqui, Mahwish
Jabeen, Almas
Irshad, Rimsha
Khan, Farooq-Ahmad
Atia-tul-Wahab,
Choudhary, M. Iqbal
Wang, Yan
author_facet Aamer, Muhammad
Siddiqui, Mahwish
Jabeen, Almas
Irshad, Rimsha
Khan, Farooq-Ahmad
Atia-tul-Wahab,
Choudhary, M. Iqbal
Wang, Yan
author_sort Aamer, Muhammad
collection PubMed
description An anabolic-androgenic synthetic steroidal drug, methasterone (1) was transformed by two fungi, Cunninghamella blakesleeana and Macrophimina phaseclina. A total of six transformed products, 6β,7β,17β-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (2), 6β,7α,17β-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (3), 6α,17β-dihydroxy-2α,17α-dimethyl-5α-androstane-3,7-dione (4), 3β,6β,17β-trihydroxy-2α,17α-dimethyl-5α-androstane-7-one (5), 7α,17β-dihydroxy-2α,17α-dimethyl-5α-androstane-3-one (6), and 6β,9α,17β-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (7) were synthesized. Among those, compounds 2–5, and 7 were identified as new transformed products. MS, NMR, and other spectroscopic techniques were performed for the characterization of all compounds. Substrate 1 (IC(50) = 23.9 ± 0.2 μg mL(−1)) showed a remarkable anti-inflammatory activity against nitric oxide (NO) production, in comparison to standard LNMMA (IC(50) = 24.2 ± 0.8 μg mL(−1)). Whereas, its metabolites 2, and 7 showed moderate inhibition with IC(50) values of 38.1 ± 0.5 μg mL(−1), and 40.2 ± 3.3 μg mL(−1), respectively. Moreover, substrate 1 was found to be cytotoxic for the human normal cell line (BJ) with an IC(50) of 8.01 ± 0.52 μg mL(−1), while metabolites 2–7 were identified as non-cytotoxic. Compounds 1–7 showed no cytotoxicity against MCF-7 (breast cancer), NCI-H460 (lung cancer), and HeLa (cervical cancer) cell lines.
format Online
Article
Text
id pubmed-8985176
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher The Royal Society of Chemistry
record_format MEDLINE/PubMed
spelling pubmed-89851762022-04-13 Structural transformation of methasterone with Cunninghamella blakesleeana and Macrophomina phaseolina Aamer, Muhammad Siddiqui, Mahwish Jabeen, Almas Irshad, Rimsha Khan, Farooq-Ahmad Atia-tul-Wahab, Choudhary, M. Iqbal Wang, Yan RSC Adv Chemistry An anabolic-androgenic synthetic steroidal drug, methasterone (1) was transformed by two fungi, Cunninghamella blakesleeana and Macrophimina phaseclina. A total of six transformed products, 6β,7β,17β-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (2), 6β,7α,17β-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (3), 6α,17β-dihydroxy-2α,17α-dimethyl-5α-androstane-3,7-dione (4), 3β,6β,17β-trihydroxy-2α,17α-dimethyl-5α-androstane-7-one (5), 7α,17β-dihydroxy-2α,17α-dimethyl-5α-androstane-3-one (6), and 6β,9α,17β-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (7) were synthesized. Among those, compounds 2–5, and 7 were identified as new transformed products. MS, NMR, and other spectroscopic techniques were performed for the characterization of all compounds. Substrate 1 (IC(50) = 23.9 ± 0.2 μg mL(−1)) showed a remarkable anti-inflammatory activity against nitric oxide (NO) production, in comparison to standard LNMMA (IC(50) = 24.2 ± 0.8 μg mL(−1)). Whereas, its metabolites 2, and 7 showed moderate inhibition with IC(50) values of 38.1 ± 0.5 μg mL(−1), and 40.2 ± 3.3 μg mL(−1), respectively. Moreover, substrate 1 was found to be cytotoxic for the human normal cell line (BJ) with an IC(50) of 8.01 ± 0.52 μg mL(−1), while metabolites 2–7 were identified as non-cytotoxic. Compounds 1–7 showed no cytotoxicity against MCF-7 (breast cancer), NCI-H460 (lung cancer), and HeLa (cervical cancer) cell lines. The Royal Society of Chemistry 2022-03-25 /pmc/articles/PMC8985176/ /pubmed/35424863 http://dx.doi.org/10.1039/d2ra01396g Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Aamer, Muhammad
Siddiqui, Mahwish
Jabeen, Almas
Irshad, Rimsha
Khan, Farooq-Ahmad
Atia-tul-Wahab,
Choudhary, M. Iqbal
Wang, Yan
Structural transformation of methasterone with Cunninghamella blakesleeana and Macrophomina phaseolina
title Structural transformation of methasterone with Cunninghamella blakesleeana and Macrophomina phaseolina
title_full Structural transformation of methasterone with Cunninghamella blakesleeana and Macrophomina phaseolina
title_fullStr Structural transformation of methasterone with Cunninghamella blakesleeana and Macrophomina phaseolina
title_full_unstemmed Structural transformation of methasterone with Cunninghamella blakesleeana and Macrophomina phaseolina
title_short Structural transformation of methasterone with Cunninghamella blakesleeana and Macrophomina phaseolina
title_sort structural transformation of methasterone with cunninghamella blakesleeana and macrophomina phaseolina
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985176/
https://www.ncbi.nlm.nih.gov/pubmed/35424863
http://dx.doi.org/10.1039/d2ra01396g
work_keys_str_mv AT aamermuhammad structuraltransformationofmethasteronewithcunninghamellablakesleeanaandmacrophominaphaseolina
AT siddiquimahwish structuraltransformationofmethasteronewithcunninghamellablakesleeanaandmacrophominaphaseolina
AT jabeenalmas structuraltransformationofmethasteronewithcunninghamellablakesleeanaandmacrophominaphaseolina
AT irshadrimsha structuraltransformationofmethasteronewithcunninghamellablakesleeanaandmacrophominaphaseolina
AT khanfarooqahmad structuraltransformationofmethasteronewithcunninghamellablakesleeanaandmacrophominaphaseolina
AT atiatulwahab structuraltransformationofmethasteronewithcunninghamellablakesleeanaandmacrophominaphaseolina
AT choudharymiqbal structuraltransformationofmethasteronewithcunninghamellablakesleeanaandmacrophominaphaseolina
AT wangyan structuraltransformationofmethasteronewithcunninghamellablakesleeanaandmacrophominaphaseolina