Synthesis and biological evaluation of novel heterocyclic derivatives of combretastatin A-4.
A novel series of combretastatin A-4 heterocyclic analogues was prepared by replacement of the B ring with indole, benzofurane or benzothiophene, attached at the C2 position. These compounds were evaluated for their abilities to inhibit tubulin assembly: derivative cis3b, having a benzothiophene, showed an activity similar to those of colchicine or deoxypodophyllotoxine. The antiproliferative and antimitotic properties of cis3b against keratinocyte cancer cell lines were also evaluated and the intracellular organization of microtubules in the cells after treatment with both stereoisomers of 3b was also determined, using confocal microscopy.
Université de Lyon, Université Lyon 1, Faculté de Pharmacie, ISPB, EA 4446 Biomolécules, Cancer et Chimiorésistances, SFR Santé Lyon-Est CNRS UMS3453-INSERM US7, 8 avenue Rockefeller, F-69373 Lyon cedex 08, France.
Thi Thanh Binh
TT
Nguyen
Thierry
T
Lomberget
Ngoc Chau
NC
Tran
Evelyne
E
Colomb
Lore
L
Nachtergaele
Sylviane
S
Thoret
Joëlle
J
Dubois
Joren
J
Guillaume
Rawad
R
Abdayem
Marek
M
Haftek
Roland
R
Barret
D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001572:Benzofurans / Q000737:chemistry; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D007211:Indoles / Q000737:chemistry; D018613:Microscopy, Confocal; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013876:Thiophenes / Q000737:chemistry
D050256:Antimitotic Agents; D001572:Benzofurans; D006571:Heterocyclic Compounds; D007211:Indoles; D013267:Stilbenes; D013876:Thiophenes; C088015:benzothiophene; C030374:indole; C058728:fosbretabulin; C105430:benzofuran; D003078:Colchicine