Expanding the chemical diversity of metal complexes provides a robust platform to generate functional bioactive reagents.

Chemical agents that specifically exploit metabolic vulnerabilities of cancer cells will be beneficial but are rare. The role oxidative phosphorylation (OXPHOS) in promoting and maintaining triple-negative breast (TNBC) growth provides new treatment opportunity. In this work, we describe AuPhos-19, a small-molecule gold(III)-based agent bearing chiral phosphine ligand selectively disrupts mitochondrial metabolism murine human TNBC not normal epithelial cells. AuPhos-19 induces potent...

c-MYC is an oncogenic transcription factor that plays a crucial role in the regulation of downstream targets involved proliferation, apoptosis, differentiation, metabolism, signaling, and immune response processes whose deregulation leads to progression different pathologies. The development selective potent small-molecule inhibitors remains grand challenge chemical biology medicine due its undruggability, derived from extensive intrinsic disorder. In this study, we identified novel dihydro...

Chemical control of mitochondrial dynamics and bioenergetics can unravel fundamental biological mechanisms therapeutics for several diseases including, diabetes cancer. We synthesized stable, water-soluble gold(III) complexes (Auraformin) supported by biguanide metformin or phenylmetformin efficacious inhibition respiration. The new compounds were characterized following the reaction [C N]-cyclometalated with respective biguanides. Auraformin is solution stable in a physiologically relevant...

Immune checkpoint blockades have revolutionized the treatment landscape for several cancer indications, yet they not gained traction in a range of other tumors such as triple-negative breast cancer. Despite durable disease control by many patients, third patients relapse due to acquired resistance. Combined immunotherapy has shown significant promise overcome these grand challenges. In this report, we describe synthesis and characterization dual-action small-molecule PARP1/PD-L1 inhibitor...

Mitochondrial structure and organization is integral to maintaining mitochondrial homeostasis an emerging biological target in aging, inflammation, neurodegeneration, cancer. The study of its functional implications remains challenging part because the lack available tools for direct engagement, particularly a disease setting. Here, we report gold-based approach perturb cancer cells. Specifically, design synthesis series tricoordinate Au(I) complexes with systematic modifications group 15...

We report a mild method for the selective deprotection of <italic>N</italic>-Boc group from structurally diverse set compounds, encompassing aliphatic, aromatic, and heterocyclic substrates by using oxalyl chloride in methanol.

Herein is reported the synthesis of two Au(III) complexes bearing (R,R)-(–)-2,3-Bis(tert-butylmethylphosphino)quinoxaline (R,R-QuinoxP*) or (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxaline (S,S-QuinoxP*) ligands. By reacting stoichiometric equivalents HAuCl4.3H2O to one equivalent corresponding QuinoxP* ligand, (R,R)-(–)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (1) and...

Abstract Direct targeting of intrinsically disordered proteins, including MYC, by small molecules for biomedical applications would resolve a longstanding issue in chemical biology and medicine. Thus, we developed gold‐based small‐molecule MYC reagents that engage inside cells modulate transcriptional activity. Lead compounds comprise an affinity ligand gold(I) or gold(III) warhead capable protein modification. Cell‐based target engagement studies via CETSA co‐immunoprecipitation reveal...

Triple-negative breast cancer (TNBC) is associated with metabolic heterogeneity and poor prognosis limited treatment options. New paradigms for TNBC remains an unmet need. Thus, therapeutics that target metabolism are particularly attractive approaches. We previously designed organometallic Au(III) compounds capable of modulating mitochondrial respiration by ligand tuning high anticancer potency in vitro vivo. Here, we show efficacious dithiocarbamate (AuDTC) compound induce dysfunction...

Metal-based drugs, such as cisplatin and auranofin, are used for the treatment of cancer rheumatoid arthritis, respectively. Auranofin other gold-derived compounds have been shown to possess anticancer, anti-inflammatory, antimicrobial, antiparasitic activity in preclinical clinical trials. Unlike platinum agents which known target DNA, gold is not well elucidated. To better understand targets effects mammalian cells, we a targeted CRISPR (ToxCRISPR) screen K562 cells identify genes that...

Abstract Background Heterotopic pregnancies are increasing in incidence with the advent of rising prevalence vitro fertilization and embryo transfer (IVF-ET) globally. Although rare, this condition is a serious potentially life-threatening gynaecological complication. Case presentation We present case 36-year-old Ghanaian woman who conceived following IVF presented two weeks after confirmation intrauterine gestation sudden onset lower abdominal pain. A diagnosis ruptured heterotopic...

Survivorship care of the cancer patient has become a growing concern among oncologists and primary physicians in communities across country. It is now recognized as distinct phase continuum care. There are an estimated 12 million Americans with history looking to their for assistance navigating difficult waters survivorship. Although concerted effort underway, there few evidence-based guidelines or recommendations managing long-term late effects adult survivors. The Children 's Oncology...

7558 Background: Lung cancer is the leading cause of death. Response and survival patients (pts) with stage III lung in minority population not well studied. Methods: 79 pts treated between 2001 2006 were studied as a retrospective cohort. Clinical data analyzed using fisher's test, chi square Kaplan Meier analyses. Results: 33 Pts had Stage IIIA; Median age at diagnosis was 58 yrs (37–75). 14 males (42.4%) 19 females (57.6%) 26 African American (78.8%) 7 Caucasians (21.2%). number co...