Synthesis and biological evaluation of combretastatin analogs as cell cycle inhibitors of the G1 to S transition in Saccharomyces cerevisiae.
A series of Z and E combretastatin A-4 analogs bearing different substituents (OH, F, NO(2), NH(2), B(OH)(2)) in the 3' position were synthesized. These derivatives and Z and E combretastatin A-1 were analysed by monitoring their ability to inhibit cell growth in Saccharomyces cerevisiae. Combretastatin A-1 (2a), A-4 (2b) and compound 2c were found to inhibit yeast growth. Moreover, combretatstatin A-4 (2b) and compound 2c induced a G1 arrest by affecting the synthesis of Clb5 protein, the principal S-phase cyclin. The G1 arrest is coincident with the activation of the stress activated kinase Snf1.
Coccetti
Paola
P
Dipartimento di Biotecnologie e Bioscienze, Università Milano-Bicocca, P.zza della Scienza, 2, 20126 Milano, Italy. paola.coccetti@unimib.it
Montano
Giuseppe
G
Lombardo
Alessandro
A
Tripodi
Farida
F
Orsini
Fulvia
F
Pagliarin
Roberto
R
D019926:Cyclin B / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D016193:G1 Phase / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
C076558:CLB5 protein, S cerevisiae; D019926:Cyclin B; D029701:Saccharomyces cerevisiae Proteins; D013267:Stilbenes; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; C058728:fosbretabulin