Identification of sulfonamide-based aromatase inhibitors in the breast cancer research

Breast cancer (BC) represents the type of cancer that most frequently affects women and one of the leading causes of death among females worldwide. Approximately 70% of cases of BC are estrogen dependent (Hormone Receptor-Positive, HR+), since high levels of these hormones are needed for its growth and proliferation. The most effective treatment for ER+ is endocrine therapy, which reduces growth rate and proliferation by modifying ER signaling. Aromatase is a key enzyme that converts androgens to estrogens by the process known as aromatization. Aromatase inhibition is an established therapeutic option for the treatment of postmenopausal BC, and current developments indicate that it will become more important over the coming years. Studies have shown that aromatase inhibitors (AIs) are effective when used as adjuvant therapy to chemotherapy and surgery in metastatic estrogen-dependent BC. AIs are categorized as either steroidal or nonsteroidal inhibitors depending on their structure scaffold. Our working group investigates the medicinal chemistry and cell biology of non-steroidal AIs, mainly exploring the introduction of rigid and highly delocalized aromatic moiety or heteroaromatic rings, discovering molecules with potent anti-aromatase activity. This talk presents a work-in-progress study of new aromatase inhibitors. I show the main results and the directions of our ongoing research, considering the impact of structure modifications on anticancer activity.