Diversity Oriented Strategy (DOS) for the Efficient Synthesis of Benzofuro[2,3-b]pyridine Derivatives with Anticancer Activity
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Link: https://doi.org/10.1002/cmdc.202400514
Title: Diversity Oriented Strategy (DOS) for the Efficient Synthesis of Benzofuro[2,3-b]pyridine Derivatives with Anticancer Activity
Authors: Reymark Ereje, Jantana Yahuafai, Theeranuch Jaroenchuensiri, Patcharaporn Supakijjanusorn, Sukanya Unson, Borwornlak Toopradab, Thanyada Rungrotmongkol, Somsak Pianwanit, Chanat Aonbangkhen, Tanatorn Khotavivattana
Abstract:
Benzofuropyridines (BFP) are polycyclic compounds with known applications in neuronal diseases. However, its derivatization patterns and anticancer potential remains unexplored. Leveraging the idea of diversity-oriented synthesis (DOS), we developed a highly efficient synthetic route for BFP, to increase the library of available analogs producing three compounds in one reaction set up, including the 2O-, 6O-, and the 1N-substituted species, also synthesizing the unusual 2-pyridone derivatives. Key bromination reaction of the BFP moiety was successfully described which can widen the available variation in the compound's structure. The cytotoxic activity of the compounds was assessed against SH-SY5Y (neuroblastoma), HepG2 (hepatocellular carcinoma), Kb (human oral epidermoid), HeLa (cervical) and MCF-7 (breast) cancer cell lines. In the series, the m-bromobenzyl (5b), methylcyano (5g) and propargyl (5h) 2O-derivatives demonstrated good selectivity against cancer cells with selectivity index (SI) of >71 for 5 g against HeLa over the normal cells, as compared to the standard drug, Doxorubicin (SI=6.7). The quantitative structure-activity relationship (QSAR) analysis revealed an impressive correlation of the defined descriptors with the bioactivity having an R2 value of 0.971 and 0.893 for Kb and HeLa respectively. Altogether, our work highlighted new information on the synthesis of BFP derivatives with potent cytotoxic activity.
Cite this:
R. Ereje, J. Yahuafai, T. Jaroenchuensiri,P. Supakijjanusorn, S. Unson, B.Toopradab, T. Rungrotmongkol, S.Pianwanit, C. Aonbangkhen, T. Khotavivattana, Diversity Oriented Strategy (DOS) for the Efficient Synthesis of Benzofuro[2,3-b]pyridine Derivatives with Anticancer Activity, ChemMedChem 2024, e202400514. https://doi.org/10.1002/cmdc.202400514
