Luo, Guoshun published the artcile3,9-di-O-substituted coumestrols incorporating basic amine side chains act as novel apoptosis inducers with improved pharmacological selectivity, COA of Formula: C9H10O3, the main research area is neoplasm antitumor coumestrol pharmacokinetics; Apoptosis; Cell cycle; Coumestrol; Estrogenic activity; Tubulin polymerization inhibitor.
There is much interest in the use of phytoestrogens such as coumestrol in breast cancer intervention due to their antiestrogenic activity and multiple modes of tumor cell death. However, the clear beneficial effects of naturally occurring estrogen mimetic coumestrol remain controversial due to exptl. evidence that it has been shown to stimulate MCF-7 cell proliferation via agonist effect on estrogen receptor at low concentration Herein, to disconnect the ER interaction and apoptosis-specific mechanism of coumestrol, various 3, 9-di-O-substituted coumestrols (7a-7e) and their furan ring-opened analogs (5a-5e) were synthesized and assessed for antiproliferative properties. Attachment of a dimethylamine-containing side chain to 3-O of coumestrol led to the most promising compound 7e (I) with improved antiproliferative activity (1.7-fold increase) against MCF-7 cells, decreased estrogen activity (>20 times weaker ERα binder) and a novel action to induce apoptosis. Mechanistic studies revealed that I is a tubulin polymerization inhibitor, which could arrest cell cycle at G2/M phase and induce apoptosis along with the decrease of mitochondrial membrane potential. In summary, such subtle modifications to the 3, 9-di-hydroxyl groups of coumestrol allow the generation of a novel apoptosis inducer with distinct pharmacol. properties, providing an excellent starting point to future development of novel tumor-vascular disrupting agents targeting tubulin.
Bioorganic Chemistry published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, COA of Formula: C9H10O3.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem