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Development of Steroidal Aromatase Inhibitors as Potential Anti-breast Cancer Agents

Breast cancer is the most prevalent type of cancer and one of the leading causes of death among all the cancers affecting women worldwide. Preliminary cause of development of tumors in the breast cancer in post-menopausal women is mostly the increased estrogen levels in the body which could be the result of overexpression of aromatase CYP450 i.e. CYP19A1. Aromatase is the only enzyme present in humans that brings about aromatization of A-ring of 19-carbon androgens to form 18-carbon estrogens. Inhibiting aromatase enzyme thereby decreasing the estrogen levels in the postmenopausal women has been considered as an important strategy for the management of breast cancer. Three generations of aromatase inhibitors including steroidal viz. testolactone, formestane, exemestane and non-steroidal viz. aminoglutethimide, fadrozole, letrozole, anastrozole, the two classes of drugs have been approved for clinical use for the treatment of breast cancer. A large number of research and review articles have been reported so far describing the therapeutic efficacy of steroidal and non-steroidal aromatase inhibitors. However, steroidal aromatase inhibitors, being more selective inhibitors and having certain other advantages, overruled the discovery of novel aromatase inhibitors compared to the non-steroidal aromatase inhibitors which lack selectivity for CYP450 aromatase. In this review, efforts have been made to describe the developments of steroidal aromatase inhibitors to date.