Synthesis and antiproliferative activity of benzo[d]isothiazole hydrazones.
Several benzo[d]isothiazole hydrazones have been evaluated for their potential antiretroviral activity. Since a number of these compounds were found to be inactive against viruses, but showed cytotoxicity at micromolar concentrations against the human CD4+ lymphocytes (MT-4) that were used to support HIV-1 growth, they were further tested for antiproliferative activity. The compounds resulted as being cytotoxic for MT-4 cells and new derivatives which were rationally designed and synthesized, were tested for antiproliferative activity against several leukaemia and solid tumour cell lines. In addition, these compounds were evaluated against "normal" cell lines. Compound 2h proved to be the most active compound and the fragment -CO-NH-N=CH-2-hydroxyphenyl was identified as being very important for biological activity, suggesting intramolecular hydrogen bond formation or favourable mutual disposition between two important centres in the pharmacophore. 1H-NMR spectra have been explained with the support of a conformational analysis.
Dipartimento Farmaceutico Università degli Studi Parma, Parco Area delle Scienze 27/A-43100 Parma, Italy. pvicini@ipruniv.cce.unipr.it
Paola
P
Vicini
Matteo
M
Incerti
Irini A
IA
Doytchinova
Paolo
P
La Colla
Bernadetta
B
Busonera
Roberta
R
Loddo
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D015394:Molecular Structure; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry*
D000970:Antineoplastic Agents; D006835:Hydrazones; D013844:Thiazoles