In vivo evaluation of the aromatase inhibition by 4-((1H-imidazol-1-yl) methyl)-2-(4-fluorophenyl)- 8-phenylquinoline
International Journal of Pharmaceutical Investigation
INTRODUCTION The most common malignancy in women is breast cancer that is the second cause of cancer death in woman after lung cancer.  The conventional treatment modalities for breast cancer are surgery, radiation therapy, hormone therapy, chemotherapy, and/or a combination of them.  Objective: Some of aromatase inhibitors (AIs) are Food and Drug Administration-approved agents which are used as first-line therapy in the treatment of endocrine-responsive breast cancer. In this study, we
... In this study, we aimed to develop new quinoline derivative with higher specificity and potency. Materials and Methods: The in vivo aromatase inhibition of these compounds was evaluated by measuring the inhibition of the androstenedione-induced uterine hypertrophy. The selectivity of aromatase inhibition has been investigated by the inhibition of adrenocorticotropic hormone stimulation on the plasma concentrations of aldosterone and cortisol. Results: Letrozole (10 µg/kg) could significantly inhibit uterine hypertrophy in positive control group that received androstenedione 30 mg/kg/day. Furthermore, quinoline derivative could decrease the androstenedione-induced uterine hypertrophy in a dose-dependent manner. Interestingly, there was no significant difference between inhibitory potency of letrozole and quinoline derivatives. High dose of letrozole could significantly decrease the serum concentration of aldosterone and cortisol as compared to control group. On the other hand, the same doses of quinoline derivative were administered; it did not show any significant effects on the serum concentration of either aldosterone or cortisol. Conclusion: This report introduced a new compound that can be considered as new lead for further investigation to explore the more potent and more selective AIs.