Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles(1).
The design and synthesis of antitumor imidazothiazole guanylhydrazones are reported. The compounds were submitted to NCI for testing. All but one were more active than methyl-GAG. A few compounds were selected for further studies in search of a possible mechanism of action. The results from these studies and a final search with the NCI COMPARE algorithm suggest that the guanylhydrazones described in this paper are acting through a novel mechanism of action.
Andreani
Aldo
A
Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy. aldo.andreani@unibo.it
Burnelli
Silvia
S
Granaiola
Massimiliano
M
Leoni
Alberto
A
Locatelli
Alessandra
A
Morigi
Rita
R
Rambaldi
Mirella
M
Varoli
Lucilla
L
Farruggia
Giovanna
G
Stefanelli
Claudio
C
Masotti
Lanfranco
L
Kunkel
Mark W
MW
D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D006835:Hydrazones; D013844:Thiazoles; D012437:Adenosylmethionine Decarboxylase