41581-85-5Relevant academic research and scientific papers
Gold(I) Phosphine Derivatives with Improved Selectivity as Topically Active Drug Leads to Overcome 5-Nitroheterocyclic Drug Resistance in Trichomonas vaginalis
Miyamoto, Yukiko,Aggarwal, Shubhangi,Celaje, Jeff Joseph A.,Ihara, Sozaburo,Ang, Jonathan,Eremin, Dmitry B.,Land, Kirkwood M.,Wrischnik, Lisa A.,Zhang, Liangfang,Fokin, Valery V.,Eckmann, Lars
, p. 6608 - 6620 (2021/05/29)
Trichomonas vaginalis causes the most common, nonviral sexually transmitted infection. Only metronidazole (Mz) and tinidazole are approved for treating trichomoniasis, yet resistance is a clinical problem. The gold(I) complex, auranofin, is active against T. vaginalis and other protozoa but has significant human toxicity. In a systematic structure-activity exploration, we show here that diversification of gold(I) complexes, particularly as halides with simple C1-C3 trialkyl phosphines or as bistrialkyl phosphine complexes, can markedly improve potency against T. vaginalis and selectivity over human cells compared to that of the existing antirheumatic gold(I) drugs. All gold(I) complexes inhibited the two most abundant isoforms of the presumed target enzyme, thioredoxin reductase, but a subset of compounds were markedly more active against live T. vaginalis than the enzyme, suggesting that alternative targets exist. Furthermore, all tested gold(I) complexes acted independently of Mz and were able to overcome Mz resistance, making them candidates for the treatment of Mz-refractory trichomoniasis.
Gold-197 m?ssbauer studies of some gold(I) thiolates and their phosphine complexes including certain antiarthritic gold drugs
Hill, David T.,Sutton, Blaine M.,Isab, Anvarhusein A.,Razi, Tahir,Sadler, Peter J.,Trooster, Jan M.,Calis, Gijs H. M.
, p. 2936 - 2942 (2008/10/08)
Structural information on 11 gold(I) thiolates and 12 phosphine-coordinated gold(I) thiolates has been collected by using 197Au M?ssbauer spectroscopy. The compounds studied include the injectable antiarthritic drugs gold sodium thiomalate (1), gold thioglucose (6), gold sodium thiosulfate (11), and the orally effective (phosphine)gold(I) thiolate auranofin (15). Isomer shifts and quadrupole coupling constants indicate that gold atoms in the 1:1 thiolates are sulfur bonded and two-coordinate. These compounds are polymeric in the solid state. This information complements previous solution studies. The M?ssbauer spectra of the (phosphine)gold complexes are characteristic and consistent with a monomeric linear SAuP linkage. The spectral parameters (IS, QS) of the phosphine complexes are approximately 2 mm s-1 larger than those of the comparable thiolates. The structural and biological significance of these data is discussed.
