Design, synthesis and biological evaluation of estradiol-chlorambucil hybrids as anticancer agents.
A series of estradiol-chlorambucil hybrids was synthesized as anticancer drugs for site-directed chemotherapy of breast cancer. The novel compounds were synthesized in good yields through efficient modifications of estrone at position 16alpha of the steroid nucleus. The newly synthesized compounds were evaluated for their anticancer efficacy in different hormone-dependent and hormone-independent breast cancer cell lines. The novel hybrids showed significant in vitro anticancer activity when compared to chlorambucil. Structure-activity relationship (SAR) reveals the influence of the length of the spacer chain between carrier and drug molecule.
Département de Chimie-Biologie, Groupe de Recherche en Oncologie et Endocrinologie Moléculaires, Université du Québec à Trois-Rivières, C.P. 500, Trois-Rivières, Québec, Canada G9A 5H7.
Atul
A
Gupta
Pijus
P
Saha
Caroline
C
Descôteaux
Valérie
V
Leblanc
Eric
E
Asselin
Gervais
G
Bérubé
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002699:Chlorambucil / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D015195:Drug Design; D004958:Estradiol / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002699:Chlorambucil; D004958:Estradiol