In vitro and in vivo antiproliferative activity of water-soluble gold(I) complexes with PTA derivatives

Abstract

Cisplatin is one of the most employed metallic complexes for cancer treatment. However, its effectiveness is hindered by toxic side effects and the occurrence of tumor resistance. Trying to overcome these drawbacks, a considerable interest in searching new metallic complexes to be used in the treatment of cancer has emerged. Among the new nonplatinum as potential anticancer drugs, gold derivatives have gained increasing attention due to their generally strong tumor cell growth inhibiting effects and the observation that many of the compounds inhibit the enzyme thioredoxin reductase (TrxR). In the design of a drug, a balance between hydrophilicity and lipophilicity is required to be water soluble and at the same time be able to pass through the phospholipid cell membrane. Accordingly, water solubility of the drugs could provide such balanced relationship. The use of water-soluble phosphanes can lead to the synthesis of water soluble or partially soluble complexes. Within this frame, here we include the synthesis of new water-soluble thiolate gold(I) derivatives with different phosphanes derived from PTA (1,3,5-triaza-7-phosphaadamantane). Some of these complexes have been screened for their antitumor activity against human colon cancer cell lines, as well as their apoptic activity evaluation and their implication in the cell cycle progression.