Coumarins as Tool Compounds to Aid the Discovery of Selective Function Modulators of Steroid Hormone Binding Proteins

Abstract

Steroid hormones play an essential role in a wide variety of actions in the body, such as in metabolism, inflammation, initiating and maintaining sexual differentiation and reproduction, immune functions, and stress response. Androgen, aromatase, and sulfatase pathway enzymes and nuclear receptors are responsible for steroid biosynthesis and sensing steroid hormones. Changes in steroid homeostasis are associated with many endocrine diseases. Thus, the discovery and development of novel drug candidates require a detailed understanding of the small molecule structure–activity relationship with enzymes and receptors participating in steroid hormone synthesis, signaling, and metabolism. Here, we show that simple coumarin derivatives can be employed to build cost-efficiently a set of molecules that derive essential features that enable easy discovery of selective and high-affinity molecules to target proteins. In addition, these compounds are also potent tool molecules to study the metabolism of any small molecule.

Recent Studies on Aromatase and EGFR Involved in Breast Cancer and their Inhibitors

“…It has been shown that 3-phenylcoumarins (31-35) (G. Luo et al, 2017;Guoshun Luo et al, 2017;S. Niinivehmas & Pentikäinen, 2021) are able to suppress BC by blocking specific hormonal enzymes like hormonal estrogen receptor-α (ER-α) as it can mimic steroid compound binding in ER and thus offer a solution to affect ER activity (Kumar, Sunita, Jha, & Pattanayak, 2018;S.…”

Substituted benzocoumarin derivatives: synthesis, characterization, biological activities and molecular docking with ADME studies

“…Coumarin derivatives readily interact with a variety of enzymes and receptors in breast cancer cells. Moreover, the coumarin-based irosustat drug is known to interact with sulfatase enzyme, indicating that coumarin derivatives are potential materials for anti-breast cancer agents [20]. In the last 30 years, doctors have made great strides in early diagnosis and treatment of the disease and in reducing breast cancer deaths.…”