Triaryl methane derivatives as antiproliferative agents.
Clotrimazole (CLT) 1, a synthetic anti-fungal imidazole derivative, inhibits tumor cell proliferation and angiogenesis. In the current study, flow cytometric analysis demonstrated that the decrease in tumor cell growth by CLT 1 was associated with inhibition of cell cycle progression at the G(1)-S phase transition, resulting in G(0)-G(1) arrest. A series of CLT 1 analogues has been generated in order to develop CLT 1 derivatives that are devoid of the imidazole moiety which is responsible for the hepatoxicity associated with CLT 1 while retaining CLT 1 efficacy. The majority of these analogues demonstrate in vitro antiproliferative activity ranging from submicromolar to micromolar concentrations.
Al-Qawasmeh
Raed A
RA
Lorus Therapeutics Inc., 2Meridian Road, M9W 4Z7, Toronto, ON, Canada.
Lee
Yoon
Y
Cao
Ming Yu
MY
Gu
Xiaoping
X
Vassilakos
Aikaterini
A
Wright
Jim A
JA
Young
Aiping
A
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D003022:Clotrimazole / Q000031:analogs & derivatives / Q000494:pharmacology; D006131:Growth Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008697:Methane / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D041681:NIH 3T3 Cells
D006131:Growth Inhibitors; D003022:Clotrimazole; D008697:Methane