Gold(I) Complexes with a Quinazoline Carboxamide Alkynyl Ligand: Synthesis, Cytotoxicity, and Mechanistic Studies

Abstract

A series of gold(I) complexes with the general formula [Au-(L2)(L')] (L2 = 4-phenyl-N-(prop-2-yn-1-yl)quinazoline-2-carboxamide, L' = PPh 3 (triphenylphosphine), 1; TPA (1,3,5-triaza-7phosphaadamantane), 2, and Me 2 -imy (1,3-dimethylimidazol-2ylidene), 3) were synthesized and fully characterized by spectroscopic methods. The alkynyl ligand L2 belongs to the quinazoline carboxamide class of ligands that are known to bind to the translocator protein (TSPO) at the outer mitochon-drial membrane. 1 and 2 exert cytotoxic effects in bladder cancer cells with IC 50 values in the low micromolar range. Further mechanistic analysis indicated that the two complexes both act by inducing reactive oxygen species and caspasemediated apoptosis. The complexes inhibit thioredoxin reductase, an established target of anticancer gold(I) complexes. Docking studies confirmed that after ligand exchange the free ligand L2 can interact with the TSPO binding site.

Recent development of gold(i) and gold(iii) complexes as therapeutic agents for cancer diseases

“…The cytotoxicity is due to the presence of gold( i ) as the free quinazoline carboxamide is inactive. 96 In 2021, the anticancer properties of complexes 105–109 were assessed against ovarian carcinoma (OVCAR-3) and human lung adenocarcinoma (HOP-62) cell lines by Babgi et al The obtained IC 50 values for complexes 105 and 106 (the aldehyde containing complexes) ranged from 12.45 to 15.86 μM. However, the Schiff base complexes 107–109 exhibited much higher anticancer activities with values ranging between 5.27 and 9.40 μM 97 (Fig.…”

“…The alkynyl ligand of the gold complex belongs to the quinazoline carboxamide class of ligands that are known to bind to the translocator protein (TSPO) at the outer mitochondrial membrane. The cytotoxicity is due to the presence of gold(I) as the free quinazoline carboxamide is inactive 96. In 2021, the anticancer properties of complexes 105-109 were assessed against ovarian carcinoma (OVCAR-3) and human lung adenocarcinoma (HOP-62) cell lines by Babgi et al The obtained IC 50 values for complexes 105 and 106 (the aldehyde containing complexes) ranged from 12.45 to 15.86 mM.…”

Survey of Recent Trends of IB-IVB Metals and Their Compounds in Cancer Treatment

“…The toxic and side effects of Au(I)-containing drugs are commonly associated with the possible formation of Au(III) [74] . Au(I) and Au(III) complexes represent a good treatment option and alternative to antineoplastic platinum therapy overcoming adverse effects and cell resistance [75][76][77][78][79][80][81][82] . Au(III) compounds are isoelectronic and isostructural with Pt(II) complexes with a square-planar geometry.…”

Recent Trends in the Development of Novel Metal-Based Antineoplastic Drugs

“…An alkynyl-activated quinazoline carboxamide was synthesized in order to produce a series of alkynyl-Au(I) complexes [ 115 ] ( Figure 32 ). Quinazoline carboxamides tend to bind to translocator protein 18kDa (TSPO), situated on the outer mitochondrial membrane [ 116 ].…”