Synthesis and biological evaluation of benzo[ d]isothiazole, benzothiazole and thiazole Schiff bases

• Published in: Bioorganic & medicinal chemistry 2003-11, Vol.11 (22), p.4785-4789
• Main Authors: Vicini, Paola, Geronikaki, Athina, Incerti, Matteo, Busonera, Bernadetta, Poni, Graziella, Cabras, Carla Alba, La Colla, Paolo
• Format: Article
• Language: English
• Subjects: Animals; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - pharmacology; Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - pharmacology; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Benzothiazoles; Biological and medical sciences; Cattle; Cell Division - drug effects; Cell Line, Tumor; Drug Evaluation, Preclinical; General aspects; HIV-1 - drug effects; Humans; Inhibitory Concentration 50; Medical sciences; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium - drug effects; Pharmacology. Drug treatments; Schiff Bases - chemical synthesis; Schiff Bases - pharmacology; T-Lymphocytes - drug effects; T-Lymphocytes - virology; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(03)00493-0

Three new series of benzo[ d]isothiazole, benzothiazole and thiazole Schiff bases were synthesized and tested in vitro with the aim of identifying novel lead compounds active against emergent and re-emergent human and cattle infectious diseases (AIDS, hepatitis B and C, tuberculosis, bovine viral diarrhoea) or against drug-resistant cancers (leukaemia, carcinoma, melanoma, MDR tumors) for which no definitive cure or efficacious vaccine is available at present. In particular, these compounds were evaluated in vitro against representatives of different virus classes, such as a HIV-1 (Retrovirus), a HBV (Hepadnavirus) and the single-stranded RNA + viruses Yellow fever virus (YFV) and Bovine viral diarrhoea virus (BVDV), both belonging to Flaviviridae. Title compounds were also tested against representatives of Gram-positive and Gram-negative bacteria ( Staphylococcus aureus, Salmonella spp.) , various atypic mycobacterial strains ( Mycobacterium fortuitum and Mycobacterium smegmatis), yeast ( Candida albicans) and mould ( Aspergillus fumigatus). None of the compounds showed antiviral or antimicrobial activity. The benzo[ d]isothiazole compounds showed a marked cytotoxicity (CC 50=4–9 μM) against the human CD4 + lymphocytes (MT-4) that were used to support HIV-1 growth. For this reason, the most cytotoxic compounds of this series were evaluated for their antiproliferative activity against a panel of human cell lines derived from haematological and solid tumors. The results highlighted that all the benzo[ d]isothiazole derivatives inhibited the growth of leukaemia cell lines, whereas only one of the above mentioned compounds ( 1e) showed antiproliferative activity against two solid tumor-derived cell lines. Three new series of benzo[ d]isothiazole, benzothiazole and thiazole Shiff bases were synthesized and tested in vitro for their antiviral, antimicrobial, antimycobacterial and antiproliferative activity.