Antiproliferative and Tubulin-Destabilising Effects of 3-(Prop-1-en-2-yl)azetidin-2-Ones and Related Compounds in MCF-7 and MDA-MB-231 Breast Cancer Cells
نویسندگان
چکیده
A series of novel 3-(prop-1-en-2-yl)azetidin-2-one, 3-allylazetidin-2-one and 3-(buta-1,3-dien-1-yl)azetidin-2-one analogues combretastatin A-4 (CA-4) were designed synthesised as colchicine-binding site inhibitors (CBSI) in which the ethylene bridge CA-4 was replaced with a β-lactam (2-azetidinone) scaffold. These compounds, together related prodrugs, evaluated for their antiproliferative activity, cell cycle effects ability to inhibit tubulin assembly. The compounds demonstrated significant vitro activities MCF-7 breast cancer cells, particularly 9h, 9q, 9r, 10p, 10r 11h, IC50 values range 10–33 nM. also potent triple-negative (TBNC) line MDA-MB-231, 23–33 nM, comparable activity CA-4. inhibited polymerisation vitro, reduction polymerization, shown interact at on tubulin. Flow cytometry that compound 9q arrested cells G2/M phase resulted cellular apoptosis. antimitotic properties human evaluated, effect organization microtubules after treatment observed using confocal microscopy. immunofluorescence results confirm is targeting mitotic catastrophe cells. In silico molecular docking supports hypothesis domain Compound microtubule-destabilising agent potential promising lead development new antitumour agents.
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ژورنال
عنوان ژورنال: Pharmaceuticals
سال: 2023
ISSN: ['1424-8247']
DOI: https://doi.org/10.3390/ph16071000