Design, Synthesis, and Structure-Activity Relationship Studies on Steroidal Aromatase and 5α-Reductase Inhibitors as Anti-Tumor Agents

This study focused on designing, synthesizing, and evaluating steroidal inhibitors for aromatase and 5α-reductase, enzymes involved in hormone-dependent cancers like breast and prostate cancer. For aromatase inhibitors, structural modifications on androstenedione revealed that a hydroxyl group at C-3, especially with 3β stereochemistry, enhanced inhibitory potency, while the carbonyl group at C-17 was crucial for activity. New derivatives of formestane and exemestane were also explored, with some showing greater efficacy than exemestane in inhibiting cancer cell proliferation. For 5α-reductase inhibitors, combining the steroid A-ring with C-17β substituents from finasteride and dutasteride resulted in potent inhibitors, particularly those with lipophilic amides. Additionally, coumarin derivatives were synthesized as potential aromatase inhibitors, opening new avenues for research.