In our pursuit to develop novel non-carbohydrate small molecule Galectin-1 Inhibitors, we have designed a series of 1-benzyl-1H-benzimidazole derivatives and demonstrated their anticancer activity. The compound 6g, 4-(1-benzyl-5-chloro-1H-benzo[d]imidazol-2-yl)-N-(4-hydroxyphenyl) benzamide was found to be most potent with an IC of 7.01 ± 0.20 µM and arresting MCF-7 cell growth at G2/M phase and S phase. Induction of apoptosis was confirmed by morphological changes like cell shrinkage, blebbing and cell wall deformation, dose dependent increase in the mitochondrial membrane potential (ΔΨm) and ROS levels. Further, dose dependent decrease in Gal-1 protein levels proves Gal-1 mediated apoptosis by 6g. Molecular docking studies were performed to understand the Gal-1 interaction with compound 6g. In addition, RP-HPLC studies showed 85.44% of 6g binding to Gal-1. Binding affinity studies by fluorescence spectroscopy and Surface Plasmon Resonance (SPR) showed that 6g binds to Gal-1 with binding constant (K) of 1.2 × 10 M and equilibrium constant K value of 5.76 × 10 M respectively.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bioorg.2019.103016 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Exploring associations between the FTO rs9939609 genotype and plasma concentrations of appetite-related hormones in adults with obesity.
PLoS One
January 2025
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
Associations between variants in the FTO locus and plasma concentrations of appetite related hormones are inconsistent, and might not work in a dose dependent fashion in people with obesity. Moreover, it is relevant to report meal related plasma concentrations of these hormones in persons with obesity given the growing interest in their pharmacological potential in obesity therapy. We find it clinically relevant to examine associations between the SNP rs9939609 genotypes and homeostatic appetite regulation in individuals with BMI ≥35 kg/m2.
View Article and Find Full Text PDFMorphogen-induced kinase condensates transduce Hh signal by allosterically activating Gli.
Sci Adv
January 2025
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Hedgehog (Hh) morphogen governs embryonic development and tissue homeostasis through the Ci/Gli family transcription factors. Here we report that Hh induces phase separation of the fused (Fu)/Ulk family kinases to allosterically regulate Ci/Gli. We find that Hh-induced phosphorylation of Fu/Ulk3 promotes SUMOylation of their inverted phosphorylation-dependent SUMOylation motifs.
View Article and Find Full Text PDFGanaxolone: A Review in Epileptic Seizures Associated with Cyclin-Dependent Kinase-Like 5 Deficiency Disorder.
Paediatr Drugs
January 2025
Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
Oral ganaxolone (ZTALMY), a synthetic analogue of the endogenous neuroactive steroid allopregnanolone, acts as a positive allosteric modulator of synaptic and extra-synaptic γ-aminobutyric acid (GABA) type A receptor function in the CNS. In the EU and the UK, it is approved for the adjunctive treatment of epileptic seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients aged 2-17 years. In a multinational phase III study (Marigold), 17 weeks' therapy with adjunctive ganaxolone, administered orally three times daily with food, significantly reduced 28-day major motor seizure frequency from baseline versus placebo in patients aged 2-19 years with CDD-associated refractory epilepsy.
View Article and Find Full Text PDFIL-22-mediated microRNA-124-3p/GRB2 axis regulates hyperproliferation and inflammatory response of keratinocytes in psoriasis.
Arch Dermatol Res
January 2025
School of Public Health, Shanxi Medical University, Taiyuan, China.
Psoriasis is an inflammatory dermatosis that features overproliferation and inflammatory reaction of keratinocytes. A study reported that IL-22 is involved in the pathogenesis of psoriasis by mediating miR-124 to regulate the expression of fibroblast growth factor receptor 2 in keratinocytes. A microRNA may target multiple target genes.
View Article and Find Full Text PDFInfluence of radiotherapy on cardiac implantable devices and leads-a single-institution analysis and critical evaluation of current guidelines.
Strahlenther Onkol
January 2025
TUM School of Medicine and Health, Department of Radiation Oncology, Technische Universität München (TUM), Klinikum rechts der Isar, Munich, Germany.
Purpose: Increasing life expectancy and advances in cancer treatment will lead to more patients needing both radiation therapy (RT) and cardiac implantable electronic devices (CIEDs). CIEDs, including pacemakers and defibrillators, are essential for managing cardiac arrhythmias and heart failure. Telemetric monitoring of CIEDs checks battery status, lead function, settings, and diagnostic data, thereby identifying software deviations or damage.
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!