Day: September 21, 2022

Saha, Achinto;Zhao, Shengyuan;Chen, Zhao;Georgiou, George;Stone, Everett;Kidane, Dawit;DiGiovanni, John published 《Combinatorial Approaches to Enhance DNA Damage following Enzyme-Mediated Depletion of L-Cys for Treatment of Pancreatic Cancer》 in 2021. The article was appeared in 《Molecular Therapy》. They have made some progress in their research.Reference of ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold The article mentions the following:

Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest forms of cancer with very few available therapeutic options. We previously reported that an engineered human enzyme, cyst(e)inase, which degrades L-cysteine (L-Cys) and cystine, inhibits growth of multiple cancer cells, including PDAC both in vitro and in vivo. Here, we show that cyst(e)inase treatment leads to increased clustered oxidative DNA damage, DNA single-strand breaks, apurinic/apyrimidinic sites, and DNA double-strand breaks (DSBs) in PDAC cells sensitive to intracellular depletion of L-Cys that is associated with reduced survival. BRCA2-deficient PDAC cells exhibited increased DSBs and enhanced sensitivity to cyst(e)inase. The blocking of a second antioxidant pathway (thioredoxin/thioredoxin reductase) using auranofin or inhibiting DNA repair using the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, led to significant increases in DSBs following cyst(e)inase treatment in all PDAC cells examined Cyst(e)inase plus olaparib also synergistically inhibited growth of sensitive and resistant PDAC cells in both xenograft and allograft tumor models. Collectively, these results demonstrate an important role for oxidative DNA damage and ultimately DNA DSBs in the anticancer action of cyst(e)inase. The data further show the potential for combining agents that target alternate antioxidant pathways or by targeting DNA repair pathways or genetic liabilities in DNA repair pathways to enhance the therapeutic action of cyst(e)inase for PDAC. The experimental procedure involved many compounds, such as ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold (cas: 34031-32-8) .

((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold(cas: 34031-32-8) is a disease-modifying antirheumatic drug (DMARD) and has been used to study the anti-proliferative effects against OVCAR-3 human ovarian carcinoma cells.Reference of ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold

Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis

Wang, Guosong;Chen, Ruiqi;Huang, Pengfei;Hong, Junping;Cao, Jiali;Wu, Qian;Zheng, Wei;Lin, Lina;Han, Qiangyuan;Chen, Yixin;Xia, Ningshao published 《Adefovir dipivoxil efficiently inhibits the proliferation of pseudorabies virus in vitro and in vivo》. The research results were published in《Antiviral Research》 in 2021.Synthetic Route of C20H36AuO9PS The article conveys some information:

Since 2011, highly pathogenic pseudorabies virus (PRV) variants that emerged on many farms in China have posed major economic burdens to the animal industry and have even recently caused several human cases of viral encephalitis. Currently, there are no approved effective drugs to treat PRV associated diseases in humans or pigs. Thus, it is important to develop a new effective drug for the treatment of PRV infection. To this end, we established a novel rapid method to screen drugs against PRV from 1818 kinds of small mol. drugs approved by the FDA. Using this method, we identified 21 kinds of them that can strongly suppress the proliferation of PRV. Mitoxantrone, puromycin dihydrochloride, mitoxantrone hydrochloride and adefovir dipivoxil effectively inhibited PRV in vitro. Of them, only adefovir dipivoxil could potently protect mice against lethal PRV infection. Our work identifies several kinds of potential therapeutics against PRV and may offer important guidance for controlling PRV epidemics and treating associated diseases in humans and animals. And ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold (cas: 34031-32-8) was used in the research process.

((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold(cas: 34031-32-8) is a gold(I)-phosphine thiolate small molecule described to produce antiinflammatory and antiarthritic effects.Synthetic Route of C20H36AuO9PS

Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis

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 published 《Gold(I) Phosphine Derivatives with Improved Selectivity as Topically Active Drug Leads to Overcome 5-Nitroheterocyclic Drug Resistance in Trichomonas vaginalis》 in 2021. The article was appeared in 《Journal of Medicinal Chemistry》. They have made some progress in their research.Electric Literature of C20H36AuO9PS The article mentions the following:

Trichomonas vaginalis causes the most common, nonviral sexually transmitted infection. Only metronidazole (Mz) and tinidazole are approved for treating trichomoniasis, yet resistance is a clin. 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, authors 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. And ((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold (cas: 34031-32-8) was used in the research process.

((2S,3R,4S,5R,6R)-3,4,5-Triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-thio)(triethylphosphine)gold(cas: 34031-32-8) is a gold(I)-phosphine thiolate small molecule described to produce antiinflammatory and antiarthritic effects.Electric Literature of C20H36AuO9PS

Reference:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis