Azolate/phosphane Gold(I) compounds in antiproliferative therapy: a new frontier for the azolate gold(I) chemistry

Azolate/phosphane Gold(I) compounds in antiproliferative therapy: a new frontier for the azolate gold(I) chemistry Azolate gold(I) phosphane compounds have become good candidate for anticancer applications.[1] It was highlighted that azolate gold(I) phosphane compounds were mostly very active in the regards of many panel of cancer cells, in addition to cis-platin resistant cells. Moreover, inhibition studies of pivotal enzymes, such as the seleno dependent ThioredoxinaReductase (TrxR), and an enzyme involved in DNA synthesis such as DeHydroFolateReductase, were carried out highlighting in both cases IC50 ranging from nano- to micromolar scale, respectively.[1][2] In order to study the effectiveness of these new azolate gold(I) phosphane compounds as potential anticancer agents, and to understand in depth the Structure Activity Relationship (SAR) relationship, different cell viability assays (MTT assays) were performed on a human in vitro model of HER2-overexpressing breast cancer: SKBR-3 cells.[3] After this preliminary screening, the most promising and effective compounds were selected to extend the study on A17 cell line, a murine preclinical model of Basal Like Breast Cancer (BLBC).[4] Hence, their efficacy in suppressing BLBC growth in vivo was tested and IHC analysis on explanted tumors were carried on. Overall, in vitro assays demonstrated a remarkable activity for those compounds having the Ph3PAu+ moiety and substituted imidazolate as co-ligands. Concerning the in vivo study the compounds act significantly delaying tumor growth. Accordingly, IHC analysis revealed a remarkable anti-angiogenic activity associated with a lower expression of proliferative markers and a higher level of apoptotic markers in treated tumours in comparison with controls. Moreover, respect to cisplatin these compounds displayed a lower nephrotoxicity, although their liver toxicity was higher. These promising results open the way to further investigations in order to understand the mechanism of action of these new azolate gold (I) posphane complexes. Leave one line blank [1] R. Galassi et al., Dalton Trans., 2012, (41), pp 5307-5318. [2] R. Galassi et al., Dalton Trans., 2015, (44), pp 3043-3056. [3] Fogh, J., Fogh J. M., Orfeo T, J Natl Cancer Inst. , 1977, (59), pp 221-6; [4] M. Galiè et al., Carcinogenesis , 2005, (11), pp 1868-1878