Synthesis, characterization and theoretical calculations of (1,2-diaminocyclohexane)(1,3-diaminopropane)gold(III) chloride complexes: in vitro cytotoxic evaluations against human cancer cell lines

Abstract

The gold(III) complexes of the type (1,2-diaminocyclohexane)(1,3-diaminopropane)gold(III) chloride, [(DACH)Au(pn)]Cl3, [where DACH = cis-, trans-1,2- and S,S-1,2-diaminocyclohexane and pn = 1,3-diaminopropane] have been synthesized and characterized using various spectroscopic and analytical techniques including elemental analysis, UV-Vis and FTIR spectroscopy; solution as well as solid-state NMR measurements. The solid-state (13)C NMR shows that 1,2-diaminocyclohexane (1,2-DACH) and 1,3-diaminopropane (pn) are strongly bound to the gold(III) center via N donor atoms. The stability of the mixed diamine ligand gold(III) was checked by UV-Vis spectroscopy and NMR measurements. The molecular structure of compound 1 (containing cis-1,2-DACH) was determined by X-ray diffraction analysis. The structure of 1 consists of [(cis-DACH)Au(pn)](3+) complex ion and chloride counter ions. Each gold atom in the complex ion adopts a distorted square-planar geometry. The structural details and relative stabilities of the four possible isomers of the complexes were also estimated at the B3LYP/LANL2DZ level of theoretical calculations. The computational study demonstrates that trans- conformations are slightly more stable than the cis- conformations. The antiproliferative effects and cytotoxic properties of the mixed ligand gold(III) complexes were evaluated in vitro on human gastric SGC7901 and prostate PC3 cancer cells using MTT assay. The antiproliferative study of the gold(III) complexes on PC3 and SGC7901 cells indicate that complex 3 (containing 1S,2S-(+)-1,2-(DACH)) is the most effective antiproliferative agent. The IC50 data reveal that the in vitro cytotoxicity of complex 3 against SGC7901 cancer cells manifested similar and very pronounced cytotoxic effects with respect to cisplatin. Moreover, the electrochemical behavior, and the interaction of complex 3 with two well-known model proteins, namely, hen egg white lysozyme and bovine serum albumin is also reported.

New bipyridine gold(III) dithiocarbamate-containing complexes exerted a potent anticancer activity against cisplatin-resistant cancer cells independent of p53 status

“…Both CV and SWV demonstrated that in the presence of lysozyme all compounds 1–3 showed a substantial decrease in the peak current as well as a clear peak potential shift (Supplementary Figures S5, S6 and S7). The significant change of their redox state due to their interaction with lysozyme suggests a significative chemical interaction of such gold compounds and proteins [36]. This chemical aspect deserves high attention because it could be involved in the mechanism of action of these innovative molecules as anticancer drugs.…”

Anticancer Activity and Apoptosis Induction of Gold(III) Complexes Containing 2,2′-Bipyridine-3,3′-dicarboxylic Acid and Dithiocarbamates

“…As a result, assorted sets of a potential anti-tumor gold(III) compounds were synthesized and characterized, which exhibited significant anti-proliferative effects in vitro under similar physiological conditions. They include the gold(III) complexes of bipyridines [ 11 , 12 , 13 , 19 , 20 , 21 , 22 , 23 ], diamines [ 16 , 17 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ], quinolones [ 16 ], dithiocarbamates [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ], and porphyrinates [ 38 , 39 ], as well as dinuclear gold(III) complexes [ 13 , 22 , 23 ] and a variety of organogold(III) compounds [ 37 , 40 , 41 , 42 ].…”

Potent In Vitro and In Vivo Anticancer Activity of New Bipyridine and Bipyrimidine Gold (III) Dithiocarbamate Derivatives

“…In parallel research, a team led by Altaf designed and synthesized other metallodrugs with anticancer activity, including gold (I) [21,22] and gold (III) complexes [23]. Together, our two research groups produced new bipyridine gold (III) dithiocarbamate complexes with nitrogen and sulfur donor ligands [24].…”