Pecnard, Shannon; Provot, Olivier; Levaique, Helene; Bignon, Jerome; Askenatzis, Laurie; Saller, Francois; Borgel, Delphine; Michallet, Sophie; Laisne, Marie-Catherine; Lafanechere, Laurence; Alami, Mouad; Hamze, Abdallah published an article in 2021. The article was titled 《Cyclic bridged analogs of isoCA-4: Design, synthesis and biological evaluation》, and you may find the article in European Journal of Medicinal Chemistry.Related Products of 2675-79-8 The information in the text is summarized as follows:
In this work, a series of cyclic bridged analogs of isocombretastatin A-4 (isoCA-4) with Ph or pyridine linkers were designed and synthesized. The synthesis of the desired analogs was performed by the formation of nitro-vinyl intermediates, followed by a Cadogan cyclization. Structure activity relationship (SAR) study demonstrates the critical role of the combination of quinaldine as ring A, pyridine as the linker, and indole as ring B in the same mol., for the cytotoxic activity. Among all tested compounds, compound I showed the highest antiproliferative activity against a panel of cancer cell lines with average IC50 values of 5.6 nM. Also, compound I showed high antiproliferative activity against the MDR1-overexpressing K562R cell line; thus, it was 1.5- and 12-fold more active than the reference compounds, isoCA-4 and CA-4, resp. Moreover, I displayed a strong antiproliferative activity against the colon-carcinoma cells (HT-29), which are resistant to combretastatin A-4 and isoCA-4, and it was found to be 8000-fold more active than natural CA-4. Compound I also effectively inhibited tubulin polymerization both in vitro and in cells, and induced cell cycle arrest in G2/M phase. Next, we demonstrated that compound I dose-dependently caused caspase-induced apoptosis of K562 cells through mitochondrial dysfunction. Finally, we evaluated the effect of compound I in human no cancer cells compared to the reference compound We demonstrated that I was 73 times less cytotoxic than isoCA-4 in quiescent peripheral blood lymphocytes (PBLs). In summary, these results suggest that compound I represents a promising tubulin inhibitor worthy of further investigation. In the experiment, the researchers used 1-Bromo-3,4,5-trimethoxybenzene(cas: 2675-79-8Related Products of 2675-79-8)
1-Bromo-3,4,5-trimethoxybenzene(cas: 2675-79-8) is an important raw material and intermediate used in organic synthesis, pharmaceuticals, agrochemicals and dyestuff.Related Products of 2675-79-81-Bromo-3,4,5-trimethoxybenzene can be used to synthesize analogs of HA14-1, which shows promising anticancer properties.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary