Exploring the synthesis and anticancer potential of L-tyrosine-platinum(II) hybrid molecules.
The search for new specific chemotherapeutic drugs designed to minimize the toxic side effects resulting from chemotherapy is still a subject of intense research. The objective of the current study was to design a non-steroidal-platinum(II) derivative that would target the estrogen receptor alpha (ERα) without triggering estrogenic cell proliferation. For this purpose, the amino acid L-tyrosine was modified and attached to a cisplatin analog. Hence, the L-tyrosine portion of the molecule could possibly act as a transporter to target the ERα protein and, by doing so concentrate the cytotoxic moiety to hormone-dependent breast cancer cells. Herein, we describe three different alternative methodologies that were used to make these new anticancer molecules. The L-tyrosine-Pt(II) hybrid 5b was made in four steps with 36% overall yield by the first method, in six steps with 11% overall yield by the second method and, in four steps with 23% overall yield by the third method. Preliminary biological activity on breast cancer cell lines indicated that the final hybrids (5a and 5b) were unfortunately inactive but their platinum(II) precursors (14a and 14b) showed activity similar to that of cisplatin.
Caroline
C
Descôteaux
Kevin
K
Brasseur
Valérie
V
Leblanc
Eric
E
Asselin
Departement de Chimie, Biochimie et Physique, Universite du Quebec a Trois-Rivieres, C.P. 500, Trois-Rivieres, Quebec, G9A 5H7, Canada. Gervais.Berube@uqtr.ca.
Gervais
G
Bérubé
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D014443:Tyrosine