Synthesis of D- and L-tyrosine-chlorambucil analogs active against breast cancer cell lines.
A series of D- and L-tyrosine-chlorambucil analogs was synthesized as anticancer drugs for chemotherapy of breast cancer. The novel compounds were synthesized in good yields through efficient modifications of D- and L-tyrosine. The newly synthesized compounds were evaluated for their anticancer efficacy in different hormone-dependent and hormone-independent (ER+ and ER-) breast cancer cell lines. The novel analogs showed significant in vitro anticancer activity when compared to chlorambucil. Structure-activity relationship (SAR) reveals both, the influence of the length of the spacer chain and the stereochemistry of the tyrosine moiety. Interestingly, the D- and L-tyrosinol-chlorambucil derivatives with 10 carbon atoms spacer are selective towards MCF-7 (ER+) breast cancer cell line.
Département de Chimie-Biologie, Groupe de Recherche en Oncologie et Endocrinologie Moléculaires, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada.
Caroline
C
Descôteaux
Valérie
V
Leblanc
Kevin
K
Brasseur
Atul
A
Gupta
Eric
E
Asselin
Gervais
G
Bérubé
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002699:Chlorambucil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry*
D000970:Antineoplastic Agents; D002699:Chlorambucil; D018719:Erb-b2 Receptor Tyrosine Kinases; D014443:Tyrosine