Facile, Single‐Step Synthesis of a Series of D‐Ring Ethisterones Substituted with 1,4‐1,2,3‐Triazoles: Preliminary Evaluation of Cytotoxic Activities

• Published in: ChemMedChem 2023-04, Vol.18 (8), p.e202200659-n/a
• Main Authors: Canseco‐González, Daniel, Rodríguez‐Victoria, Isaac, Apan‐Ramírez, Teresa, Viviano‐Posadas, Alejandro O., Serrano‐García, Juan S., Arenaza‐Corona, Antonino, Orjuela, Adrian L., Alí‐Torres, Jorge, Dorazco‐González, Alejandro, Morales‐Morales, David
• Format: Article
• Language: English
• Subjects: 1-4,1,2,3-triazoles; Adenocarcinoma; Adenocarcinoma of Lung; anticancer agents; Antineoplastic Agents - chemistry; Atom economy; Cell Line, Tumor; Cell Proliferation; Chemical synthesis; Chronic myeloid leukemia; click chemistry (CuAAC); Cytotoxicity; Deoxyribonucleic acid; DNA; DNA - pharmacology; DNA-docking simulation; Drug Screening Assays, Antitumor; Ethisterone - pharmacology; Glioblastoma; Humans; Infrared spectroscopy; Leukemia; Lung cancer; Lungs; Magnetic resonance spectroscopy; Mass spectrometry; Mass spectroscopy; medicinal chemistry; Molecular Docking Simulation; Molecular Structure; Myeloid leukemia; NMR; NMR spectroscopy; Nuclear magnetic resonance; Single crystals; steroids; Structure-Activity Relationship; Substitutes; Toxicity; Triazoles; Triazoles - chemistry; Tumor cell lines
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.202200659

A series of new D‐ring ethisterones substituted with 1,4‐1,2,3‐triazoles were obtained in a facile manner via click chemistry reactions. The new compounds were characterized by multinuclear NMR spectroscopy, mass spectrometry, IR and unequivocally by single crystal X‐ray diffraction studies for compound 1. The cytotoxic activity of these derivatives was tested against a series of human cancer cell lines including human glioblastoma (U‐251), human prostatic adenocarcinoma (PC‐3), human colorectal adenocarcinoma (HCT‐15), human mammary adenocarcinoma (MCF‐7), human chronic myelogenous leukemia (K562), and human lung adenocarcinoma (SKLU‐1). Derivatives (3, X=Cl) and (5, X=I) showed promising cytotoxicity activities for leukemia adenocarcinoma (K562) and lung adenocarcinoma (SKLU). CI50% of K562: 11.72±0.9 μM (3) and 24.50±1.0 μM (5). CI50% of SKLU: 14.9±0.8 μM (3) and 46.0±2.8 μM (5). In addition, DNA docking simulations showed that all compounds interact with DNA through crosslink instrastrand p‐alkyl‐like interactions. Facile single‐step syntheses of a series of D‐ring ethisterones substituted with 1,4‐1,2,3‐triazoles were conducted. Preliminary evaluation of their cytotoxic activities against human cancer cell lines has revealed promising cytotoxicities. For instance, activities against leukemia, lung cancer, and cancer‐type cells were observed for two of these compounds, with CI50 for K562: 11.72±0.9 μM (3) and SKLU: 14.9±0.8 μM (3).