Synthesis and biological evaluation of novel unsaturated carboxysteroids as human 5α-reductase inhibitors : a legitimate approach
Copyright © 2012 Elsevier Masson SAS. All rights reserved..
In the present study, novel steroidal 17a-substituted 3-cyano-17a-aza-D-homo-3,5-androstadien-17-ones (12-19) and 17a-substituted 17-oxo-17a-aza-D-homo-3,5-androstadien-3-oic acids (20-26) were synthesized from dehydroepiandrosterone acetate (6) along with 17-oxo-19-nor-3,5-androstadien-3-oic acid (30) through a multistep synthesis. Compounds were evaluated for their in vitro 5α-reductase inhibitory activity by measuring the conversion of [(3)H] androstenedione in human embryonic kidney (HEK) cells. In vivo 5α-reductase inhibitory activity was also determined using rat prostate weighing method. Compounds 21-23 and 25 showed potent inhibition of 5α-reductase II enzyme with IC(50) values of 54.1 ± 9.5, 22.1 ± 2.4, 72.8 ± 2.3 and 26.5 ± 4.4 nM respectively as compared to Finasteride (30.3 nM) along with a significant (p < 0.05) reduction in rat prostate weight.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:54 |
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| Enthalten in: |
European journal of medicinal chemistry - 54(2012) vom: 09. Aug., Seite 728-39 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Aggarwal, Saurabh [VerfasserIn] |
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| Links: |
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| Themen: |
409J2J96VR |
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| Anmerkungen: |
Date Completed 07.12.2012 Date Revised 21.11.2013 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejmech.2012.06.026 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM21927021X |
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| 100 | 1 | |a Aggarwal, Saurabh |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Synthesis and biological evaluation of novel unsaturated carboxysteroids as human 5α-reductase inhibitors |b a legitimate approach |
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| 500 | |a Date Revised 21.11.2013 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2012 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a In the present study, novel steroidal 17a-substituted 3-cyano-17a-aza-D-homo-3,5-androstadien-17-ones (12-19) and 17a-substituted 17-oxo-17a-aza-D-homo-3,5-androstadien-3-oic acids (20-26) were synthesized from dehydroepiandrosterone acetate (6) along with 17-oxo-19-nor-3,5-androstadien-3-oic acid (30) through a multistep synthesis. Compounds were evaluated for their in vitro 5α-reductase inhibitory activity by measuring the conversion of [(3)H] androstenedione in human embryonic kidney (HEK) cells. In vivo 5α-reductase inhibitory activity was also determined using rat prostate weighing method. Compounds 21-23 and 25 showed potent inhibition of 5α-reductase II enzyme with IC(50) values of 54.1 ± 9.5, 22.1 ± 2.4, 72.8 ± 2.3 and 26.5 ± 4.4 nM respectively as compared to Finasteride (30.3 nM) along with a significant (p < 0.05) reduction in rat prostate weight | ||
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| 700 | 1 | |a Thareja, Suresh |e verfasserin |4 aut | |
| 700 | 1 | |a Bhardwaj, T R |e verfasserin |4 aut | |
| 700 | 1 | |a Haupenthal, Jörg |e verfasserin |4 aut | |
| 700 | 1 | |a Hartmann, R W |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Manoj |e verfasserin |4 aut | |
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