Synthesis of Gold(I) Derivatives Bearing Alkylated 1,3,5‐Triaza‐7‐phosphaadamantane as Selective Anticancer Metallodrugs

Abstract

The alkylation of one of the nitrogen atoms of the molecule 1,3,5,triaza‐7‐phosphaadamantane (PTA) with para ‐substituted benzylic units and the l ‐phenylalanine methyl ester moiety are reported. The crystalline structures of the two alkylated PTA species [PTA‐CH 2 ‐ p ‐COOH‐C 6 H 4 ]Br ( 1a ) and [PTA‐CH 2 ‐ p ‐CH 2 COOH‐C 6 H 4 ]Br ( 2 ) reveal the presence of interactions between the bromide anion and the OH group of the acid moiety. Bis‐phosphane derivatives were prepared by the alkylation of two PTA molecules with a dibromide salt to afford more water‐soluble species. The corresponding mono‐ and dinuclear chloro‐, thiocyanato‐ and pentafluorophenyl gold(I) derivatives are described. Most of the new complexes have been tested as anticancer agents, exhibiting higher cytotoxicity than cisplatin against human colon cancer cell lines. Some of them display low cytotoxicity towards differentiated cells (non‐carcinogenic), as determined from viability studies, thereby demonstrating a significant specificity in this type of cancer.