In the present paper, on the basis of molecular hybridization, a series of 4,6-dihydrazone pyrimidine derivatives containing the pyridine moiety were synthesized, structurally characterized, and evaluated in vitro for their antitumor activity. According to the results, all the tested compounds demonstrated broad-spectrum antitumor activity against selected tumor cell lines (MCF-7, BGC-823, A549, and BEL-7402) and no obvious toxicity toward normal cells HL-7702. In particular, compounds and were found to be the most promising antitumor agents among the tested compounds against BGC-823 cells (IC = 9.00 μM and 7.89 μM) and BEL-7402 cells (IC = 6.70 μM and 7.66 μM), respectively. Compounds and exhibited higher potency against BGC-823 and BEL-7402 than the positive control 5-FU (IC = 15.18 μM and 15.81 μM). Further mechanism investigations demonstrated that compounds and could significantly increase the level of cellular ROS and induce early apoptosis of BGC-823 cells in a dose-dependent manner. Moreover, the DNA binding results from UV/Vis, CD spectroscopy, and molecular docking studies indicated that and bind with DNA via groove binding and partial intercalation. These results demonstrated that and may serve as novel lead compounds for the discovery of more dihydrazone pyrimidine derivatives with improved antitumor potency and selectivity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9822369 | PMC |
| http://dx.doi.org/10.3390/molecules28010187 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Background: The addition of durvalumab or pembrolizumab to gemcitabine and cisplatin (GP) has been approved to statistically improve survival outcomes in patients with advanced biliary tract cancer. However, since the survival time was only prolonged by about two months, doubts have been raised. In this analysis, we aimed to evaluate the efficacy of combining durvalumab or pembrolizumab with GP chemotherapy.
View Article and Find Full Text PDFAbnormal ac4C modification in metabolic dysfunction associated steatotic liver cells.
Sci Rep
January 2025
Department of Pharmacy, Affiliated Hospital of Southwest Jiao Tong University, The Third People's Hospital of Chengdu, Chengdu, 610014, China.
The pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear due to the complexity of its etiology. The emerging field of the epitranscriptome has shown significant promise in advancing the understanding of disease pathogenesis and developing new therapeutic approaches. Recent research has demonstrated that N4-acetylcytosine (ac4C), an RNA modification within the epitranscriptome, is implicated in progression of various diseases.
View Article and Find Full Text PDFSulfoxidation of pyrimidine thioate derivatives and study their biological activities.
Sci Rep
January 2025
Chemistry Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt.
In a quest to innovate biologically active molecules, the benzoylation of 4,6-dimethylpyrimidine-2-thiol hydrochloride (1) with benzoyl chloride derivatives was employed to produce a series of pyrimidine benzothioate derivatives (2-5). Subsequent sulfoxidation of these derivatives (2-5) using hydrogen peroxide and glacial acetic acid yielded a diverse array of pyrimidine sulfonyl methanone derivatives (6-9). In parallel, the sulfoxidation of pyrimidine sulfonothioates (10-12) yielded sulfonyl sulfonyl pyrimidines (13-15), originating from the condensation of compound 1 with sulfonyl chloride derivatives.
View Article and Find Full Text PDFDearomative Addition-Hydrogen Autotransfer for Branch-Selective -Heteroaryl C-H Functionalization via Ruthenium-Catalyzed C-C Couplings of Diene Pronucleophiles.
J Am Chem Soc
January 2025
Department of Chemistry, University of Texas at Austin, Austin 78712, Texas, United States.
Article Synopsis
- A new method for C-H functionalization of heteroaryl compounds is introduced, which involves a process called dearomative addition followed by hydrogen autotransfer.
- This process starts with the hydroruthenation of dienes to create allylruthenium nucleophiles, leading to branched C-C coupling products through addition and β-hydride elimination.
- The study also details the formation of enantiomerically enriched heteroarylethyl alcohols and amines through oxidative cleavage and dynamic kinetic asymmetric reduction, supported by density functional theory calculations linking regioselectivities to molecular factors.
Updates on Intrinsic Medicinal Chemistry of 1,4-dihydropyridines, Perspectives on Synthesis and Pharmacokinetics of Novel 1,4-dihydropyrimidines as Calcium Channel Blockers: Clinical Pharmacology.
Curr Top Med Chem
January 2025
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka, India.
Background: Several chemical studies described the physiological efficacy of 1,4- dihydropyridines (DHPs). DHPs bind to specific sites on the α1 subunit of L-type calcium channels, where they demonstrate a more pronounced inhibition of Ca2+ influx in vascular smooth muscle compared to myocardial tissue. This selective inhibition is the basis for their preferential vasodilatory action on peripheral and coronary arteries, a characteristic that underlies their therapeutic utility in managing hypertension and angina.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!