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

IF 3.4 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2025-08-11 DOI:10.1002/cmdc.202500146

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

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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.

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吲哚偶联二氢苯并[c]菲菲啶的细胞毒、抗菌和硅基Pks13抑制性能。

吲哚和苯并菲菲啶作为潜在的抗癌和抗菌剂引起了人们的极大兴趣。本文报道了新的和已知的吲哚偶联二氢苯并[c]菲的合成及其生物活性。在所研究的化合物中，2j对耐药金黄色葡萄球菌、表皮葡萄球菌和屎肠球菌表现出有效的选择性活性。此外，根据计算机分析推断，1a-c和2a可能通过抑制Pks13酶特异性靶向耐多药结核分枝杆菌G122。此外，化合物1g对MCF-7（乳腺）和PC-3（前列腺）人癌细胞系的作用比顺铂更有效，而化合物2b对PC-3和SW-480（结肠）细胞系的作用几乎与顺铂一样有效。化合物1a和1g表现出显著的选择性指数值，具有良好的抗菌和抗癌作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

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