A novel chiral oxazoline copper(ii)-based complex inhibits ovarian cancer growthin vitroandin vivoby regulating VEGF/VEGFR2 downstream signaling pathways and apoptosis factors

Abstract

A novel chiral oxazoline copper (II)-based complex {[Cu(C13H14NO3S)2]}2 (Cu-A) was synthesized by in-situ reaction using L-Methioninol and 4-Hydroxyisophthalaldehyde, sodium hydroxide and copper (II) nitrate trihydrate as reactants. Its crystal structure...

Arene–Arene Coupled Disulfamethazines (or Sulfadiazine)-Phenanthroline-Metal(II) Complexes were Synthesized by In Situ Reactions and Inhibited the Growth and Development of Triple-Negative Breast Cancer through the Synergistic Effect of Antiangiogenesis, Anti-Inflammation, Pro-Apoptosis, and Cuproptosis

“…In addition, two chiral tetranucleate copper-based complexes were prepared into nanoparticles, and their stability under physiological conditions was observed by transmission electron microscopy, and their cellular uptake was investigated by ICP-MS. The results showed that these two copper-based complexes could stably enter MDA-MB-231 cells and HUVECs under physiological conditions. (b) Here, the uptake of HA-Cu, HA-Co, and HA-Ni by the MDA-MB-231 cells was analyzed using ICP-MS because of HA-Cu, HA-Co, and HA-Ni not having fluorescence properties and some limited conditions. After MDA-MB-231 cells were treated with HA-Cu (5.0 μM, 7.5 μM), HA-Co (30.0 μM, 60.0 μM), and HA-Ni (40 μM, 80.0 μM) for 6 h, respectively, the level of copper, cobalt, and nickel in the MDA-MB-231 cells was evaluated by ICP-MS. As shown in Figure A – C, the intracellular copper levels in cells treated with HA-Cu, cobalt levels in cells treated with HA-Co, and nickel levels in cells treated with HA-Ni were all elevated compared to the control group, exhibiting a positive correlation with the concentrations of HA-Cu, HA-Co, and HA-Ni, respectively.…”

“…When VEGFA binds to VEGFR2 receptors, VEGFR2-mediated signaling pathways are activated, thus promoting the growth, proliferation, and migration of tumor vascular endothelial cells. − It can be seen that the VEGF/VEGFR2 signaling pathway is closely related to the formation of new blood vessels in tumor. Erk1/2, AKT, FAK, and their phosphorylated proteins p-Erk1/2, p-AKT, and p-FAK downstream of the VEGF/VEGFR2 signal transduction pathway can regulate cell proliferation, survival, migration, and tumor angiogenesis. (b) The expression of VEGFR2 along with various other genes associated with angiogenesis is controlled by FAK, and VEGFR2 is positively correlated with FAK in breast cancer patients . FAK is a tyrosine kinase at the intersection of Erk1/2, PI3K/Akt, MAPK, and JAK/STAT signaling pathways.…”

“…Bax/Bcl-2 mediates the apoptotic pathway of endoplasmic reticulum stress. When Bax and Bcl-2 combine into a dimer, the antiapoptotic capacity of Bcl-2 is diminished. (c) We investigated the effect of HA-Cu on the expression of Bcl-2 and Bax by western blot method. As documented in Figure G – I, in comparison to the control group, HA-Cu downregulates Bcl-2 expression and upregulates Bax expression in a dose-dependent manner.…”

“…As one of the important trace elements in the human body is copper, copper acts as an important role in many cellular mechanisms and signaling pathways. According to reports, active copper-based complexes have been reported to display multiple biological roles such as antitumor, − inhibition of tumor angiogenesis, − anti-inflammation, antivirus, , and even can load siRNA into tumor cells and vascular endothelial cells to perform the synergistic effect of vector chemotherapy and siRNA gene therapy . Early copper-based complex anticancer agents are mainly DNA-targeting drugs, topoisomerase I, II inhibitors, and proteasome inhibitors, while multifunctional anticancer copper-based complexes with synergistic effects of antitumor angiogenesis, anti-inflammation, and killing tumor cells have rarely been reported.…”

“…Sulfonamide is one of the earliest chemically synthesized antimicrobials, and its chemically modified derivatives play an important role in combating bacteria, fighting cancer, alleviating inflammation, and defending against oxidative stress. , Sulfamethazine is an antimicrobial sulfonamide, which is mainly used to treat various infections of livestock . Phenanthroline has a large π-bond and a rigid planar structure, which is often used in the design of metal complex drugs to enhance the activity of metal-based complexes. (a) In this study, using sulfamethazine, o -phenanthroline, copper perchlorate hexahydrate, cobalt acetate tetrahydrate, and nickel chloride hexahydrate as raw materials, Cu­(II)-based complex HA-Cu, Co­(II)-based complex HA-Co, and Ni­(II)-based complex HA-Ni were synthesized by in situ reaction. Schemes – show the synthesis routes.…”