Gold(I) Analogues of a Platinum−Acridine Antitumor Agent Are Only Moderately Cytotoxic but Show Potent Activity against Mycobacterium tuberculosis

Abstract

A series of cationic gold(I) complexes containing 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea (1), [AuL(1)]n+ (where L is Cl−, Br-, SCN−, PEt3, PPh3, or 1), derived from a class of analogous platinum(II) antitumor agents, has been synthesized. Unlike platinum, gold does not form permanent adducts with DNA, and its complexes are two orders of magnitude less cytotoxic in non-small-cell lung cancer cells than the most active platinum-based agent. Instead, several gold analogues show submicromolar and selective antimicrobial activity against Mycobacterium tuberculosis.

Synthesis and antimicrobial activities of gold(I) sulfanylcarboxylates

“…In this last field, the compounds under investigation include a major collection of the type R 3 PAuL, in which the gold atom is coordinated to a phosphine ligand and L is an O- [26,27], N- [28,29], Cl- [30] or S- [29,[31][32][33][34][35] 2 ], Na 3 [Au(mna) 2 ] (H 2 mna 02-mercaptonicotinic acid) [13] and the cationic complexes [Au(L) 2 ](NO 3 ) 3 (L01-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) [34]. For the latter ligand, compounds of the type [Au(L)]Br, [Au(L)] SCN and [Au(L)]Cl were also prepared [34] and the coexistence of an S-donor ligand and a Cl ligand was also described for [LAuCl] (where L 02,3-diphenyl-1,3,4-thiadiazolium-5-thiolato-S exo ) [36].…”

Oxyhalogen-sulfur chemistry: Kinetics and mechanism of oxidation of n-acetylthiourea by aqueous bromate and acidified bromate

“…ACTU has no absorbance in the visible region, and thus the aqueous bromine peak at 390 nm is isolated and can be used for analytical determination of bromine at the end of the reaction. This spectrophotometric method worked for a limited range of oxidant to reductant ratios; R = [BrO 3 -] 0 /[ACTU] 0 . At values of R greater than 1.6; the observed final absorbance of bromine saturated, and further increases in oxidant did not produce any changes in observed final bromine concentrations.…”

“…essentially buffered. None of the other reagents' concentrations, [BrO 3 -] t , [ACTU] t could be determined at the onset of formation of bromine such that no relevant kinetics constants could be evaluated for the rate of formation of bromine. Acid did not alter final amount of bromine obtained based on stoichiometry R2, but accelerated the rate of attainment of the final bromine concentrations.…”

“…1 Thiourea and its derivatives are thus a vast group of very active biological molecules. [2][3][4][5][6][7][8] Major pathway to their bioactivation is oxidative and specifically via S-oxygenation in which there is a successive addition of oxygen to the sulfur center until oxidative saturation is attained at sulfate. [9][10][11] Small molecule thioureas are oxygenated predominantly by catalysis from the flavin-containing monooxygenases 12,13 to form reactive sulfenic acids that reversibly react with glutathione [14][15][16][17][18][19] to drive oxidative stress through a redox cycle.…”

Chemotherapeutic Strategies and Targets Against Resistant TB

“…Eiter et al (Eiter et al, 2009) In a series of Ruthenium (II) phosphine/picolinate complexes, Pavan et al (Pavan et al, 2010) reported MIC values of 0.78 and 0.26 g/mL for compounds 62 and 63, respectively, against H37Rv ATCC 27294 using REMA (Resazurin Microtiter Assay) method (Palomino et al, as cited in Pavan et al, 2010). No toxicity data, however, was reported in the article.…”