We present the synthesis and characterization of six new heteroleptic osmium(II) complexes of the type [Os(C^N)(N^N)]OTf (N^N = 2,2'-bipyridine and dipyrido[3,2-:2',3'-]quinoxaline; C^N = deprotonated methyl 1-butyl-2aryl-benzimidazolecarboxylate) with varying substituents in the R3 position of the phenyl ring of the cyclometalating C^N ligand. The new compounds are highly kinetically inert and absorb a full-wavelength range of visible light. An investigation of the antiproliferative activity of the new compounds has been performed using a panel of human cancer and noncancerous 2D cell monolayer cultures under dark conditions and green light irradiation. The results demonstrate that the new Os(II) complexes are markedly more potent than conventional cisplatin. The promising antiproliferative activity of selected Os(II) complexes was also confirmed using 3D multicellular tumor spheroids, which have the characteristics of solid tumors and can mimic the tumor tissue microenvironment. The mechanism of antiproliferative action of complexes has also been investigated and revealed that the investigated Os(II) complexes activate the endoplasmic reticulum stress pathway in cancer cells and disrupt calcium homeostasis.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10131226 | PMC |
http://dx.doi.org/10.1021/acs.inorgchem.3c00501 | DOI Listing |
J Med Chem
December 2024
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
In this study, we discovered and identified a novel AXL/triple angiokinase inhibitor by rational structural modification based on the structure of triple angiokinase inhibitor Nintedanib. We found that potently inhibited AXL expression with the IC value of 3.75 nM and possessed similar inhibitory activity on KDR as Nintedanib.
View Article and Find Full Text PDFMol Cancer Ther
December 2024
Boehringer Ingelheim (Austria), Vienna, Austria.
KRASG12C selective inhibitors, such as sotorasib and adagrasib, have raised hopes of targeting other KRAS mutant alleles in cancer patients. We report that KRAS wild-type amplified tumor models are sensitive to treatment with the small molecule KRAS inhibitors BI-2493 and BI-2865. These pan-KRAS inhibitors directly target the "OFF" state of KRAS and result in potent anti-tumor activity in pre-clinical models of cancers driven by KRAS mutant proteins.
View Article and Find Full Text PDFSmall
December 2024
Department of Chemistry, Indian Institute of Technology, Kharagpur, West Bengal, 721302, India.
Anticipating intramolecular excited-state proton-coupled electron transfer (PCET) process within dinuclear Ir-photocatalytic system via the covalent linkage is seminal, yet challenging. Indeed, the development of various dinuclear complexes is also promising for studying integral photophysics and facilitating applications in catalysis or biology. Herein, this study reports dinuclear [Ir(bis{imidazo-phenanthrolin-2-yl}-hydroquinone)(ppy)] (1) complex by leveraging both ligand-centered redox property and intramolecular H-bonding for exploring dual excited-state proton-transfer assisted PCET process.
View Article and Find Full Text PDFBioorg Med Chem Lett
December 2024
Department of Chemistry, PDEA's Baburaoji Gholap College, Sangvi, Pune 27, India. Electronic address:
The current comprehensive study showcases a meticulous synthesis of novel class of α-benzilmonoxime thiocarbohydrazide (BMOTC) derivatives, and manifesting their multifaceted potential as antibacterial, antifungal, and anticancer agents. The synthesis of target compounds was performed in three phases using literature methods. In the first step, benzilmonoxime is synthesized using benzil and hydroxyl amine hydrochloride, followed by benzilmonoxime imine using thiocarbohydrazide.
View Article and Find Full Text PDFEur J Med Chem
December 2024
Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China. Electronic address:
Targeting XPO1 inhibition has emerged as a promising therapeutic strategy in cancer treatment. Despite the numerous XPO1 inhibitors reported to date, no XPO1 degraders have been disclosed. In this study, we reported the design, synthesis and biological characterization of small-molecule XPO1 degraders based upon the proteolysis targeting chimera (PROTAC), marking the first public disclosure of XPO1 degraders.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!