Synthesis, antitumor and anti-HIV activities of benzodithiazine-dioxides

• Published in: Bioorganic & medicinal chemistry 2006-05, Vol.14 (9), p.2985-2993
• Main Authors: Brzozowski, Zdziasław, Sączewski, Franciszek, Neamati, Nouri
• Format: Article
• Language: English
• Subjects: 8-Chloro-7-R 1-6-R 2-3-R 3-imidazo[1,2- b][1,4,2]benzodithiazines; Anhydrides - chemistry; Anti-HIV activity; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; Antiviral agents; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Chlorine - chemistry; Drug Evaluation, Preclinical; Esters - chemistry; General aspects; HIV-1 - drug effects; Human immunodeficiency virus 1; Humans; Imidazoles - chemistry; Medical sciences; Methylation; Molecular Structure; Oxygen - chemistry; Pharmacology. Drug treatments; Structure-Activity Relationship; Synthesis; Thiazines - chemical synthesis; Thiazines - chemistry; Thiazines - pharmacology
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2005.12.024

Several 8-chloro-7-R 1-6-R 2-3- R 3-imidazo[1,2- b][1,4,2]benzodithiazine 5,5-dioxide derivatives ( 9– 11, 16– 19, and 21– 24) have been synthesized as potential antitumor or anti-HIV agents. The in vitro antitumor and anti-HIV-1 activities of the compounds were determined in a panel of cell lines. The benzodithiazine-dioxide 10 showed 50% growth inhibitory activity in low micromolar against most cells. It was particularly effective in leukemia, lung, melanoma, ovarian, and renal cancer cells with GI 50 values of 1–2 μM. Interestingly, benzodithiazine-dioxide 16 showed remarkable anti-HIV-1 activity with 50% effective concentration EC 50 value of 0.94 μM and no significant cytotoxicity at 200.0 μM.