Three new series of phenyl dihydropyridazinone derivatives 4b-8i have been designed, synthesized and evaluated for their anticancer activity against different cancer cell lines. Nine compounds showed strong inhibitory activity, among which compound 8b exhibited potent activity against PC-3 cell line with IC value of 7.83 µM in comparison to sorafenib (IC 11.53 µM). Compounds 6a, 6c, 7f-h and 8a-d were further screened for their B-Raf inhibitory activity where seven compounds 7f-h and 8a-d showed high B-Raf inhibition with ranges of IC values 70.65-84.14 nM and 24.97-44.60 nM, respectively when compared to sorafenib (IC 44.05 nM). Among the tested compounds, 8b was the most potent B-Raf inhibitor with IC value of 24.79 nM. Cell cycle analysis of MCF-7 cells treated with 8b showed cell cycle arrest at G2-M phase with significant apoptotic effect. Molecular modeling study was performed to understand the binding mode of the most active synthesized compounds with B-Raf enzyme.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bioorg.2020.104148 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Broadband Long Wavelength Light Promotes Myopic Eye Growth and Alters Retinal Responses to Light Offset in Chick.
Invest Ophthalmol Vis Sci
January 2025
School of Psychology and Public Health, La Trobe University, Melbourne, Australia.
Purpose: Prolonged exposure to broadband light with a short-wavelength (blue) or long-wavelength (orange/red) bias is known to impact eye growth and refraction, but the mechanisms underlying this response are unknown. Thus, the present study investigated the effects of broadband blue and orange lights with well-differentiated spectrums on refractive development and global flash electroretinography (gfERG) measures of retinal function in the chick myopia model.
Methods: Chicks were raised for 4 days with monocular negative lenses, or no lens, under blue, orange, or white light.
Screening of obstructive sleep apnea and diabetes mellitus -related biomarkers based on integrated bioinformatics analysis and machine learning.
Sleep Breath
January 2025
Department of Respiratory and Critical Care Medicine, Medical School of Nantong University, Nantong Key Laboratory of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, China.
Background: The pathophysiology of obstructive sleep apnea (OSA) and diabetes mellitus (DM) is still unknown, despite clinical reports linking the two conditions. After investigating potential roles for DM-related genes in the pathophysiology of OSA, our goal is to investigate the molecular significance of the condition. Machine learning is a useful approach to understanding complex gene expression data to find biomarkers for the diagnosis of OSA.
View Article and Find Full Text PDFCorrection to: Constructing, in silico, molecular self‑aggregates and micro‑hydrated complexes of oxirene and thiirene.
J Mol Model
January 2025
Department of Physics, Savitribai Phule Pune University, Pune, 411007, MH, India.
Molecular structure characteristic of coals of different rank.
J Mol Model
January 2025
School of Chemical and Environmental Engineering, China University of Mining and Technology-Beijing, Haidian District, Ding No.11 Xueyuan Road, Beijing, 100083, People's Republic of China.
Context: Understanding the structural characteristics of coal at the molecular level is fundamental for its effective utilization. To explore the molecular structure characteristic, the long-flame coal from Daliuta (DLT), coking coal from Yaoqiao (YQ), and anthracite from Taixi (TX) were investigated using various techniques such as elemental analysis, Fourier transform infrared spectroscopy, solid-state C nuclear magnetic resonance spectroscopy, and X-ray photoelectron spectroscopy. Based on the structural parameters, the coal molecular model was constructed and optimized.
View Article and Find Full Text PDFIntegrating machine learning with mendelian randomization for unveiling causal gene networks in glioblastoma multiforme.
Discov Oncol
January 2025
Department of Medical Imaging, Shenzhen Longhua District Key Laboratory of Neuroimaging, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China.
Background: Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with poor prognosis and limited treatment options. Despite advances in understanding its molecular mechanisms, effective therapeutic strategies remain elusive due to the tumor's genetic complexity and heterogeneity.
Methods: This study employed a comprehensive analysis approach integrating 113 machine learning algorithms with Mendelian Randomization (MR) analysis to investigate the molecular underpinnings of GBM.
Want 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!