Synthesis of Novel Analogues of Marine Indole Alkaloids: Mono(indolyl)-4-trifluoromethylpyridines and Bis(indolyl)-4-trifluoromethylpyridines as Potential Anticancer Agents

• Published in: Bioorganic & medicinal chemistry Vol. 9; no. 7; pp. 1773 - 1780
• Main Authors: Xiong, Wen-Nan, Yang, Cai-Guang, Jiang, Biao
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.07.2001; Elsevier Science
• Subjects: Alkaloids - chemical synthesis; Alkaloids - chemistry; Alkaloids - pharmacology; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Crystallography, X-Ray; General aspects; Indoles - chemistry; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Models, Molecular; Pharmacology. Drug treatments; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - pharmacology; Antineoplastic agent; Human; Nitrogen heterocycle; Lung; P388-Leukemia; Cytotoxicity; In vitro; Pyridine derivatives; Cell line; Structure activity relation; Six membered ring; Bicyclic compound; Aromatic compound; Fluorine Organic compounds; Indole derivatives; Chemical synthesis; Tumor cell
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(01)00070-0

Mono(indolyl)-4-trifluoromethylpyridines and bis(indolyl)-4-trifluoromethylpyridines were synthesized using Suzuki cross-coupling reaction between 2-chloro-4-trifluoromethylpyridine 9, 2,6-dichloro-4-trifluoromethylpyridine 6 or 2,6-dichloro-3-cyano-4-trifluoromethylpyridine 23 and N-tosyl-3-indolylboronic acid 10. They were evaluated for cytotoxic activity against P388 and A-549 cells with IC 50 values. 4-Trifluoromethyl-2,6-bis[3′-( N-tosyl-6′-methoxylindolyl)]pyridine 18 was identified as the most potent in this series. The synthesis and anticancer activities of the mono(indolyl)-4-trfluoromethylpyridines and bis(indolyl)-4-trifluoromethylpyridines are reported.