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

Abstract

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 microM) 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.

• Authors: Paola Vicini, Athina Geronikaki, Matteo Incerti, Bernadetta Busonera, Graziella Poni, Carla Alba Cabras, Paolo La Colla
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 11 Issue 22 Pg. 4785-9 (Nov 03 2003) ISSN: 0968-0896 [Print] England
• PMID: 14556794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Anti-Infective Agents
• Antineoplastic Agents
• Benzothiazoles
• Schiff Bases
• Thiazoles
• benzothiazole

Topics

• Animals
• Anti-HIV Agents (chemical synthesis, pharmacology)
• Anti-Infective Agents (chemical synthesis, pharmacology)
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Benzothiazoles
• Cattle
• Cell Division (drug effects)
• Cell Line, Tumor
• Drug Evaluation, Preclinical
• HIV-1 (drug effects)
• Humans
• Inhibitory Concentration 50
• Microbial Sensitivity Tests
• Molecular Structure
• Mycobacterium (drug effects)
• Schiff Bases (chemical synthesis, pharmacology)
• T-Lymphocytes (drug effects, virology)
• Thiazoles (chemical synthesis, chemistry, pharmacology)