Characterization of benzofuran derivatives: Crystal structure, DFT analysis and antitumor activity

Benzofuran derivatives are important in the treatment of human diseases owing to their anti-inflammatory, antitumor, antibacterial, antifungal and antitubercular effects. Herein, two benzofuran derivatives—5-hydroxy-2-phenyl-1-benzofuran-3-carboxylic acid ethyl ester (A) and 2,6-diphenylbenzo[1,2-: 4,5-b’]difuran-3,7-dicarboxylic acid diethyl ester (B)—were synthesized using a one-step method and fully characterized. The crystal structures of compounds A and B were determined. In the Hirshfeld surface analysis, the H···H interactions of compounds A and B accounted for the largest proportion of surface contacts, and they are one of the main driving forces for the arrangement of surface molecules. FMOs analysis indicated that compound A exhibits low reactivity, and its energy gap is relatively close to that of Paclitaxel, showing good stability; in contrast, the electrons of compound B are more easily excited, leading to higher reactivity. MEP studies revealed that compound A is prone to targeted electrophilic/nucleophilic reactions, although its charge intensity is slightly lower than that of Paclitaxel. Compound B shows weaker directionality of nucleophilic reaction sites, which results in its poor target-binding ability. Finally, the results of in vitro antitumor activity evaluation showed that compound A exhibited significant proliferation-inhibitory effects on HCT-116, MCF-7, and A549 cell lines, with activity comparable to that of Paclitaxel. In contrast, compound B displayed tumor cell selectivity, and its activity was weaker than that of Paclitaxel. Both compounds demonstrated potential antitumor activity.