Effective anti-aromatase therapy to battle against estrogen-mediated breast cancer: Comparative SAR/QSAR assessment on steroidal aromatase inhibitors

A large number of world women populations are suffering from breast cancer. It is increasing day by day that is quite alarming. The major reason behind breast tumors is upregulation of estrogen which is dependent on aromatase. Aromatase inhibitors (AIs) have opened up a new era to combat the battle against estrogen-mediated breast cancer. Despite several advantages, various adverse effects have limited the use of AIs. Therefore, it is still a demanding and challenging job to design selective AIs with fewer adverse effects. In this article, comparative quantitative structure-activity relationship (QSAR) study of steroidal aromatase inhibitors (SAIs) have been discussed in details to get an insight into the structural and physicochemical properties of SAIs controlling the aromatase inhibitory activity. This study reflects that SAIs should possess smaller shape and size with less bulky substituents having lesser polarity and less steric effect along with greater hydrophobicity for the higher aromatase inhibitory activity. This study will obviously shed light into the newer idea for the medicinal chemists to design and discover novel, effective and less toxic SAIs to combat the life-threatening breast cancer as well as to initiate a modern era in breast cancer drug discovery. [Display omitted] •Aromatase regulates the production of estrogen in breast cancer.•Steroidal aromatase inhibitors (SAIs) are effective in treating estrogen-mediated breast cancer.•A comparative QSAR study of the existing SAIs has been performed.•Effective SAIs should possess smaller size and shape, less polarity along with greater hydrophobicity.