Cytotoxic, Antibacterial, and in Silico Pks13 Inhibitory Properties of Indole-Coupled Dihydrobenzo[c]phenanthridines

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Reyna Martha Gallegos-Alvarado, Adriana Romo-Pérez, Luis Demetrio Miranda, María Del Rayo Camacho-Corona, Alfonso Dueñas-González, Johannes Kirchmair, Abraham García

Published: 11 Aug 2025, Last Modified: 22 Jan 2026ChemMedChemEveryoneRevisionsBibTeXCC BY-SA 4.0
Abstract: The indoles and benzo[c]phenanthridines have attracted much interest as potential anticancer and antibacterial agents. Herein, the synthesis and bioactivity of new and known indole-coupled dihydrobenzo[c]phenanthridines are reported. Among the investigated compounds, 2j displays potent and selective activity against drug-resistant Staphylococcus aureus, S. epidermidis, and Enterococcus faecium strains. In addition, 1a-c and 2a specifically target the multidrug-resistant Mycobacterium tuberculosis G122, possibly by inhibiting the Pks13 enzyme, as deduced from the in silico analyses. Additionally, compound 1g is more potent than cisplatin against MCF-7 (breast) and PC-3 (prostate) human cancer cell lines, whereas 2b is found to be almost as active as cisplatin against PC-3 and SW-480 (colorectal) cell lines. Compounds 1a and 1g display remarkable selectivity index values, thus being promising antibacterial and anticancer hits.