Details

Autor(en) / Beteiligte

• Atanasov, Gjorgji
• Rusew, Rusi I
• Gelev, Vladimir M
• Chanev, Christo D
• Nikolova, Rosica
• Shivachev, Boris L
• Petrov, Ognyan I
• Apostolova, Margarita D

Titel

New Heterocyclic Combretastatin A-4 Analogs: Synthesis and Biological Activity of Styryl-2(3 H )-benzothiazolones

Ist Teil von

• Pharmaceuticals (Basel, Switzerland), 2021-12, Vol.14 (12), p.1331

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2021

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Here, we describe the synthesis, characterization, and biological activities of a series of 26 new styryl-2(3H)-benzothiazolone analogs of combretastatin-A4 (CA-4). The cytotoxic activities of these compounds were tested in several cell lines (EA.hy926, A549, BEAS-2B, MDA-MB-231, HT-29, MCF-7, and MCF-10A), and the relations between structure and cytotoxicity are discussed. From the series, compound ( )-3-methyl-6-(3,4,5-trimethoxystyryl)-2(3 )-benzothiazolone ( ) exhibits the most potent cytotoxic activity (IC 0.13 ± 0.01 µM) against EA.hy926 cells. not only inhibits vasculogenesis but also disrupts pre-existing vasculature. is a microtubule-modulating agent and inhibits a spectrum of angiogenic events in EA.hy926 cells by interfering with endothelial cell invasion, migration, and proliferation. also shows anti-proliferative activity in CA-4 resistant cells with the following IC values: HT-29 (0.008 ± 0.001 µM), MDA-MB-231 (1.35 ± 0.42 µM), and MCF-7 (2.42 ± 0.48 µM). Cell-cycle phase-specific experiments show that treatment results in G2/M arrest and mitotic spindle multipolarity, suggesting that drug-induced centrosome amplification could promote cell death. Some -treated adherent cells undergo aberrant cytokinesis, resulting in aneuploidy that perhaps contributes to drug-induced cell death. These data indicate that spindle multipolarity induction by has an exciting chemotherapeutic potential that merits further investigation.