Synthesis, Characterization, and Antileishmanial Activity of Neutral Gold(I) Complexes with N-heterocyclic Carbene Ligands Bearing Sulfur-Containing Side Arms

Abstract

With an estimated annual incidence of one million cases, leishmaniasis is one of the top five vector-borne diseases. Currently available medical treatments involve side effects, including toxicity, non-specific targeting, and resistance development. Thus, new antileishmanial chemical entities are of the utmost interest to fight against this disease. We have shown in previous studies that gold(I) complexes bearing N-heterocyclic carbene (NHC) ligands with nitrogen or sulfur containing side arms have interesting biological activities in the field of cancer, malaria and leishmaniasis. The present study evaluates the in vitro antileishmania effects on L.infantum axenic amastigotes and their cytotoxicity for the human Thp1 cell line of a new family of 6 new imidazolium salts and their corresponding neutral (NHC)Au(I)Cl complexes. All new compounds have been characterized by classical analytical methods and five gold complexes have been evidenced by X-ray structure determination. We showed that one proligand has moderate activity (IC 50 = 8.24 µM) while 4 of 6 gold complexes have IC 50 values in the µM range (0.15-1.3 µM) including 3 with SI's between 46 and 108. These results suggest remarkable leishmanicidal activity in vitro for 3 new neutral (NHC)Au(I)Cl complexes making them candidate for further in vivo studies which are under investigation.

Synthesis and Antimicrobial Activity of Carbene Complexesof the Imidazole, Benzimidazole and 1,2,4‐Triazole Series

“…Table 3 shows indicators of the sensitivity of microorganisms to the action of the investigated substances (according to method A), which display that compounds 3 b, 4 b, 6 c and especially 8 a, 14 are proved to be active. The activity of the compounds was compared with that under equal conditions for the well-known antimicrobial preparation 1-cetylpyridinium chloride 15, [35] which has a related structure with some of the synthesized substances (11)(12)(13). .0(2) 15 [35] 0.5 0 0 14.4(3) 0 10.0(2) 0.1 0 0 12.0(2) 0 7.0(1) [a] Control values correspond to 0 mm.…”

“…Carbenoid compounds (organic salts and carbene complexes of transition metals) are well known for their biological activities, [1][2][3][4][5] including antitumor, antimicrobial (antibacterial, antifungal), [6][7][8][9][10] antimalarial, [11] antileishmanial, [12] antinematodic [13] actions, properties of inhibitors of mosquitoes, [14] enzymes, [15] etc. Among them, derivatives of fluorine-containing, carbene-heterocyclic derivatives (e. g., PEP-PSI-complexes), copper carbene complexes and complexes with long-chain aliphatic substituents have not been studied enough.…”