BackgroundOvarian cancer (OvCA) exhibits a distinctive tendency toward peritoneal metastasis, a pathological process that greatly affects disease progression and postoperative recurrence. Understanding the biological mechanisms underlying this metastatic cascade is critical for improving prognosis and developing targeted therapeutic strategies. This study investigated the functional role of TROP2 in extracellular vesicles (EVs) from ovarian cancer ascites, and revealed how TROP2 induces mesothelial-mesenchymal transition (MMT) through EV-mediated intercellular communication. This process remodeled the mesothelial microenvironment into a pro-metastatic environment that enables peritoneal dissemination.MethodsEVs were isolated from ascites and cell culture supernatants through differential centrifugation combined with ultracentrifugation. After incubation with mesothelial cells, Western blot analysis, migration assays, and adhesion assays were performed to assess the induction of mesenchymal phenotype. Through proteomic profiling analysis of ascitic EVs, the differential protein TROP2 was identified and subsequently verificated clinical samples. TROP2 expression was modified through lentiviral transfection, and an orthotopic xenograft mouse model of ovarian cancer was established to evaluate tumor growth and metastasis through in vivo bioluminescence live imaging.ResultsEVs secreted by ovarian cancer cells induced phenotypic changes in mesenchymal cells and enhanced their adhesion to cancer cells. Proteomic analysis identified TROP2 as a differentially expressed protein in ascitic EVs. Phenotypic experiments indicated that EVs from ovarian cancer deliver TROP2 to peritoneal mesothelial cells, where it induces MMT and promotes peritoneal colonization in vitro. In the orthotopic mouse model of ovarian cancer, injection of TROP2-enriched EVs promoted peritoneal metastasis. Mechanistic investigations revealed that TROP2 induced the MMT process in mesothelial cells through activating the TNF-α/NF-κB pathway. Furthermore, treatment with quinazoline (QNZ), the TNF-α/NF-κB pathway inhibitor effectively reversed the TROP2 induced mesenchymal phenotype in mesothelial cells.ConclusionThis study is the first to identify the pivotal role of TROP2 from ascitic EV in promoting metastatic dissemination by activating the TNF-α/NF-κB signaling axis. By remodeling the peritoneal microenvironment, TROP2 facilitates metastatic spread. These findings provide novel molecular insights into the mechanism of ovarian cancer peritoneal metastasis and offer significant implications for clinical translation.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13048-025-01845-6.

6-PPD triggered lipid metabolism disorder and inflammatory response in larval zebrafish (Danio rerio) by regulating PPARγ/NF-κB pathway.

Understanding the aqueous chemistry of quinoline and the diazanaphthalenes: insight from DFT study

Background and Aims: Alzheimer's disease is a neurodegenerative disorder in which the death of brain cells causes memory loss and cognitive decline. It is one of the leading causes of mortality worldwide. Several different hallmarks of the disease have been reported such as low levels of acetylcholine, deposits of β-amyloid around neurons, hyperphosphorylated tau protein, oxidative stress, etc. Pharmacotherapy for this disease currently depends on using acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. They provide only symptomatic relief and mostly targets cognitive revival. Quinazoline derivatives were recently reported as being a valuable template in the treatment of many neurodegenerative disorders. Quinazoline based compounds were declared as being potential anti AD agents. This research focuses on the synthesis of novel quinazoline derivatives 3 and 4. Methods: Novel quinazoline derivatives 3 and 4 were synthesized starting from 2-(methylamino)benzamide by consecutive steps. The structures of these compounds have been characterized using different analytical and spectral methods: TLC, GC-MS, 1 H-NMR and 13C-NMR. Results: This study revealed the synthesis of the novel compounds 3 and 4 with excellent yields equalling 97% and 73.1% respectively. Conclusion: Novel quinazoline derivatives compounds 3 and 4 were obtained. These compounds might be promising lead compounds for potential poly-functional anti-Alzheimer's agents in future work.

Parkinson's disease (PD) is one of the most disabling diseases of the central nervous system, seriously affecting health and quality of life for the elderly. The present study aimed to explore the effects of nuclear receptor subfamily4 groupA member2 (Nurr1) and nuclear factor‑κB (NF‑κB) on the progression of Parkinson's disease (PD). Pheochromocytoma (PC12) cells were pretreated with the NF‑κB inhibitor quinazoline (QNZ) or transfected with small interfering (si)RNA‑NF‑κB, followed by the addition of lipopolysaccharide (LPS). After culturing for 24h, Cell Counting Kit‑8 (CCK‑8) was utilized to measure cell viability. Next, the expression levels of interleukin (IL)‑1β, IL‑6 and tumor necrosis factor(TNF)‑α were determined using the relevant Enzyme‑linked immunosorbent assay kits. Expression levels of p65, tyrosine hydroxylase (TH), α‑Synuclein (A‑SYN) and Nurr1 were examined by immunofluorescence and western blotting. CCK‑8 results showed that the cell viability was significantly reduced in the LPS group than in the control group (P<0.05), whereas QNZ and si‑NF‑κB demonstrated significantly enhanced viability induced by LPS (P<0.05). After LPS induction, the levels of IL‑1β, IL‑6 and TNF‑α were significantly elevated when compared with those in the control group (P<0.05), whereas QNZ and NF‑κB interference partially restored their levels. Additionally, after LPS induction, the expression of p65 and A‑SYN was higher, while the expression of TH and Nurr1 was lower. However, QNZ and NF‑κB treatment significantly reversed the expression levels induced by LPS (P<0.05). Finally, it was observed that NF‑κB may be negatively associated with Nurr1. In conclusion, inhibition of NF‑κB may reduce the production of inflammatory factors by upregulating Nurr1 and TH and downregulating A‑SYN, thus relieving the inflammatory response in PD.

Indole-3-carbaldehydes Arylhydrazones as Multisite C-Nucleophiles in the Reactions with Quinazoline

Previous studies have shown that Quinazoline (QNZ) plays extremely important roles in the cellular physiological activity, but it has been rarely examined on cell behavior following intervertebral disc degeneration (IVDD). The aim of this study was to investigate whether QNZ mediates oxidative stress and inflammation contributed to IL-1β-induced nucleus pulposus (NP) cells degeneration in vitro. NP were isolated cells from human disc samples collected from patients and the IL-1β-induced NP cells degenerated model was constructed. The cells were randomly divided into 3 groups, namely, Control group, IL-1β group (10 µM), QNZ + IL-1β group (containing 10 nM QNZ and 10 µM IL-1β). Then, the cell viability was determined by CCK-8 assay, and the levels of collagen I, collagen II, aggrecan, p16, p53, β-galactosidase (β-gal), antioxidant enzymes, 8-hydroxy-2-deoxyguanosine (8-OHdG), NF-κB/MAPKs signaling-related proteins and inflammatory factors were examined using Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in NP cells. Finally, the expressions of IL-1β, IL-6, and TNF-α in the cell supernatants were also determined by enzyme-linked immunosorbent assay (ELISA). This study showed that IL-1β promoted the progress of IDD, with markedly increased expressions of collagen I, p16, p53, and β-gal, as well as decreased expressions of collagen II and aggrecan. However, QNZ treatment could reverse the effects of IL-1β. It was found that cell proliferation was increased, ROS level was decreased, antioxidant enzymes were upregulated, and inflammatory factors were reduced after QNZ stimulation. Moreover, NF-κB/MAPKs signaling proteins IKKβ, IκBα, p65, ERK, JNK, and p38 were significantly dephosphorylated by QNZ. These results indicated that QNZ prevented NP degradation via restraining oxidative stress and inflammation through inhibition of the NF-κB/MAPKs signaling pathway. QNZ may become a novel insight into the therapy of IVDD in the future.

The reactions of quinazoline with 1,3,5-trimethoxybenzene, 3- and 4-methylbenzene-1,2-diamines, and 1-(4-methoxybenzylidene)-2-phenylhydrazine on heating in the presence of trifluoroacetic acid afforded the corresponding stable C–C σ-adducts.

Recent investigations of azidoazomethine-tetrazole (azide-tetrazole) tautomeric equilibrium reported from 2014 to 2019 are summarized. Pyridine, pyrimidine, triazine, azole derivatives and their annulated congeners – purines, quinolines, quinazolines are described.

Abstract The current study reports design and diversity-oriented synthesis of novel heterocycles incorporating thioureido linkage and mesoionic compounds could find new applications in biology. Employing reagent-based skeletal diversity approach; a facile synthesis of quinazoline and sydnone moiety has been accomplished. The synthesized compounds were characterized by IR and 1 H NMR-spectral data, and elemental analysis. The structural and electronic properties of newly synthesized compounds have been explored theoretically by performing semi-empirical molecular orbital theory at the level of PM6 of theory. Henceforth, computational chemistry can assist the experimental chemist or it can challenge the experimental chemist to find entirely new chemical objects. Keywords: Computational study, quinazoline, mannich base, thioureido linkage Cite this Article Modi J. Computational Study of Some Heterocyclic Scaffolds Derived from Quinazoline and Mannich Base Sydnone. Journal of Modern Chemistry & Chemical Technology . 2018; 9(3): 8–12p.

Ionic-Liquid-Mediated Syntheses of Fused Pyrimidines and Quinazolines

Quinazolines are medicinally important as anti-convulsant, anti-cancer, anti-microbial, and anti-tubercular properties etc. They target epidermal growth factor receptors on tumor cells. This work is aimed to synthesize a new series of quinazoline derivatives which could deliver drug specifically to the EGFR over expressing tumors. A series of novel Schiff’s base analogues were developed by in silico screening methods. The drug likeness of the analogues was analyzed by using Molinspiration software. Biological activities of these analogues were evaluated by using PASS software. The candidates which obeyed Lipinski rule of five and having suitable anti-cancer and anti-microbial activity were taken for docking studies using Schrodinger software. All the proposed derivatives were docked with various protein targets obtained from PDB, using GLIDE software and satisfactory docking energy scores were obtained. Selected 10 derivatives of quinazoline have been synthesized by anthranilamide and benzaldehyde as starting materials. These analogues were purified by analyzing its melting point, Rf value. These were further characterized by FT-IR, 1H NMR and MASS spectral studies. The anti-cancer activity of these derivatives was done by MTT assay against HeLa cell lines, LD50 values were calculated by Brine Shrimp Lethality Assay. From these experiments it is clearly revealed that these analogues possess good anti-cancer activity and are good lead compounds against tumors.

СИНТЕЗ И ПУТИ ОБРАЗОВАНИЯ ГИДРОКСИФЕНИЛЗАМЕЩЕННЫХ БЕНЗ[4,5]ИМИДАЗОЛО-1,2,3,4,5, 6-ГЕКСАГИДРО[1,2-а]ХИНАЗОЛИНОВ

A novel quinazoline-based analog induces G2/M cell cycle arrest and apoptosis in human A549 lung cancer cells via a ROS-dependent mechanism

Objective: The present investigation is designed to synthesize some new isomeric series of quinazoline-4-one/4-thione derivatives, depending upon on the pharmacophoric model of in-vivo anticancer activity by modifying the structures retaining the fundamental structural features for the activity and screened for their antitumor properties. Methods: A new series of 7-chloro-3-[substituted (amino/phenyl amino)]-2-phenyl quinazolin-4 (3H)-one/thione derivatives and 1-(7-chloro-4-oxo/-2-phenylquinazoline-3 (4H-yl)) substituted urea derivatives were synthesized. The reaction scheme proceeds through 7-chloro-2-phenyl-4H-benzo [d] [1, 3] oxazin-4-one which is the intermediate one. The structures of the newly synthesized compounds were characterised from infrared (IR), H 1 nuclear magnetic resonance (NMR) and mass spectra (m/z) and elemental analysis. The in-vivo antitumor activity was evaluated by body weight analysis, mean survival time and percentage increase in life span methods in Swiss albino mice bearing Ehrilich ascites carcinoma (EAC). Result: The physico-chemical and spectroscopic data established the synthesis of quinazoline derivatives with a common pharmacophore. The synthesized compounds were evaluated for their antitumor properties. Among the newly quinazoline derivatives screened, six compounds (IIh, IIi, IIj, IIIh, IIIi, IIIj)) have shown significant antitumor activity. Conclusion: The quinazoline derivatives obtained from the present study indicates that the amino group at 3 rd position and urea/thiourea group in phenyl hydrazine ring at 3 rd position of quinzoline skeleton are essential for antitumor activity. Compounds IIh, IIi, IIj, IIIh, IIIi and IIIj were found to be biologically active which may be useful as potential resource for the discovery of anti-tumor compound having common quinazoline pharmacophore with lesser toxic effects.

Base Promoted Annulation of Carbodiimides to Access of Quinazoline and Their Derivatives

Ultrasounds promoted synthesis of 4(3H)-quinazolines under Yb(OTf)3 catalysis

Indazoloquinazolines are a class of heterocyclic compounds consisting of fused indazole and quinazoline fragments that can be connected with nitrogen atom as a fusion point. The tetracyclic scaffolds built that way include indazolo[2,3- c ]quinazolines, indazolo[2,3- a ]quinazolines, and indazolo[3,2- b ]quinazolines. The natural occurrence of this compound class is rare, however, the indazolo-fused quinazolines possess a wide range of biological activities. Among those, indazolo[2,3- a ]quinazolines have shown high antibacterial activity. The synthetic routes towards indazoloquinazolines can be categorised into several groups: 1) metal-catalyzed and metal-free intramolecular cyclizations; 2) metal-catalyzed and metal-free intermolecular reactions; 3) reductive intramolecular cyclization; 4) multicomponent assembly reactions. How to Cite Roopan, S. M.; Palaniraja, J. Chem. Heterocycl. Compd. 2016 , 52 , 93. [ Khim. Geterotsikl. Soedin. 2016 , 52 , 93.] For this article in the English edition see DOI 10.1007/s10593-016-1838-2

A new and facile CuCl2 center dot 2H(2)O-catalyzed one-pot three-component synthesis for quinazolines

Objective To explore the relationship between microRNA (miRNA)-200c expression,epithelial-mesenchymal transition (EMT) and the sensitivity to gefitinib in colon cancer cells.Methods The inhibitory effects of gefitinib on four types of colon cancer cell lines (HT29,SW620,HCT1116,SW480) were examined by cell counting kit-8 (CCK-8) assay.The expressions of miRNA-200c,epithelial marker (E-cadherin) and mesenchymal markers (vimentin and zinc finger Ebox binding homeobox 1 ZEB 1) at mRNA level in four types of colon cancer cell lines were detected by fluorescence quantitative polymerase chain reaction.The expressions of E-cadherin,vimentin and ZEB 1 at protein level were determined by Western blot.After up-or down-regulated the expression of miRNA-200c,the changes of the expression of EMT related genes and the sensitivity to gefitinib were observed.Results HT29 cells were most sensitive to gefitinib (IC50 =(7.70 ± 0.31) μmol/L),in which the expressions of both miRNA-200c and E-cadherin were the highest,and the expressions of vimentin and ZEB1 were extremely low.HCT116 and SW480 were moderately sensitive to gefitinib (IC50=(11.88±0.97) and (16.63±0.45) μmol/L),and the expressions of miRNA-200c and Ecadherin were moderate.SW620 cell line was most insensitive to gefitinib (IC50 =(26.43 ± 3.68)μmol/L),the expressions of miRNA-200c and E-cadherin were the lowest.The expressions of vimentin and ZEB 1 in SW620 were higher than that of the other three types of cell lines.After upregulated the expression of miRNA 200c,the expression of E-cadherin in SW620 cells increased,the expression of ZEB 1 and vimentin decreased,and the sensitivity to gefitinib increased.After downregulated the expression of miRNA-200c,the expression of E-cadherin in HT29 cells decreased,the expression of ZEB 1 and vimentin increased,and the sensitivity to gefitinib decreased.Conclusion miRNA-200c may up-regulate the expression of E-cadherin through EMT regulation,and then influence the sensitivity to gefitinib in colon cancer cells. Key words: Epithelial cells; Colonic neoplasms; MicroRNAs; Quinazolines; Cadherins; Cell Line, tumor