Diversity Oriented Strategy (DOS) for the Efficient Synthesis of Benzofuro[2,3-b]pyridine Derivatives with Anticancer Activity.

Autor: Ereje R; Center of Excellence in Natural Products, Department of Chemistry, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand.; Department of Physical Sciences, College of Science, University of the Philippines Baguio, Baguio City, 2600, Philippines., Yahuafai J; Clinical Research Section, Division of Research and Academic Support, National Cancer Institute, Bangkok, 10400, Thailand., Jaroenchuensiri T; Center of Excellence in Natural Products, Department of Chemistry, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand., Supakijjanusorn P; Center of Excellence in Natural Products, Department of Chemistry, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand., Unson S; Center of Excellence in Natural Products, Department of Chemistry, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand., Toopradab B; Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand., Rungrotmongkol T; Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand., Pianwanit S; Center of Excellence in Computational Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand., Aonbangkhen C; Center of Excellence in Natural Products, Department of Chemistry, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand., Khotavivattana T; Center of Excellence in Natural Products, Department of Chemistry, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok, 10330, Thailand.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2024 Oct 18, pp. e202400514. Date of Electronic Publication: 2024 Oct 18.
DOI: 10.1002/cmdc.202400514
Abstrakt: 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 1 N-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 (5 b), methylcyano (5 g) and propargyl (5 h) 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 R 2 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.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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