Abstract
The synthesis and aromatase inhibitory activity of androst-4-en-, androst-5-en-, 1β,2β-epoxy- and/or androsta-4,6-dien-, 4β,5β-epoxyandrostane-, and 4-substituted androst-4-en-17-oxime derivatives are described. Inhibition activity of synthesized compounds was assessed using aromatase enzyme and [1β-3H]androstenedione as substrate. Most of the compounds displayed similar to or more aromatase inhibitory activity than formestane (74.2%). 4-Chloro-3β-hydroxy-4-androsten-17-one oxime (14, 93.8%) showed the highest activity, while 4-azido-3β-hydroxy-4-androsten-17-one oxime (17, 32.8%) showed the lowest inhibitory activity for aromatase.
Highlights
Breast cancer is the most common cause of death from cancer in women
Over the past two decades, highly potent and specific aromatase inhibitors have been studied as a logical treatment strategy and some have already been approved for clinical use
The syntheses of androst-4-en, androst-5-en- and androsta-4,6-diene-17-oxime are shown in Scheme 1
Summary
Breast cancer is the most common cause of death from cancer in women. Estrogens are involved in numerous physiological processes including the development and maintenance of the female sexual organs, the reproductive cycle, reproduction, and various neuroendocrine functions. Compounds that inhibit enzyme aromatase have applications in the treatment of advanced estrogen-dependent breast cancer [6,7]. Over the past two decades, highly potent and specific aromatase inhibitors have been studied as a logical treatment strategy and some have already been approved for clinical use. These include two classes of compounds: steroids, exemestane (Aromasin®), formestane (Lentaron®) and nonsteroids, anastrozole (Arimidex®) and letrozole (Femara®) (Figure 1). Analogs of 4-androstenedione, have been described, including 4-hydroxy- [9], 4-amino- [10], 4-mercapto- [11], 4-(O-alkyl)-, 4-(O-aryl)-, 4-(alkyl)- and 4-(aryl) [12] derivatives, which have been evaluated clinically. Synthesized compounds primarily evaluated their aromatase inhibitory activity by the radiometric method in vitro
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