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Leptin is a pleiotropic hormone which, upon binding to its cognate leptin receptor (LepR), induces the activation of the JAK2/ERK, STAT3/STAT5 and IRS/PI3 kinase signaling cascades. Hence, we used molecular docking and a chemical library to identify 18 compounds with high probability of interacting with the leptin binding domain (LBD) of LepR. 6 out of 18 compounds were selected based on toxicological and physicochemical properties to evaluate their effect in the formation of Leptin-LepR complex using ELISA assays. The six compounds showed discreet but significant modulation on the complex formation. These results have important implications in proposing novel strategies for modulating the formation of the Leptin-LepR complex, as therapeutic alternatives for patho-physiologies where the formation of this complex is deregulated.
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http://dx.doi.org/10.6026/973206300200404 | DOI Listing |
Arch Pharm (Weinheim)
September 2025
Chemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Through applying the hybridization technique, new coumarin derivatives (2-17) were prepared with substitution at coumarin C-3 utilizing various heterocyclic derivatives, aiming to afford multi-target carbonic anhydrases (CAs) IX/XII and topoisomerase II (Topo II) inhibitors with potent antiproliferative activity. Eight different cell lines were used to evaluate the growth inhibition percentages (GI%) of cancer cells determined by coumarin analogues 1-17. Analogues 16 and 17 had the most substantial cytotoxic effects, achieving mean GI% of 86.
View Article and Find Full Text PDFMol Inform
September 2025
Department of Computational Chemistry, "Coriolan Drăgulescu" Institute of Chemistry Timișoara, Romanian Academy, Timișoara, Romania.
Docking is a structure-based cheminformatics tool broadly employed in early drug discovery. Based on the tridimensional structure of the protein target, docking is used to predict the binding interactions between the protein and a ligand, estimate the corresponding binding affinity, or perform virtual screenings (VSs) to identify new active compounds. This study introduces the ligand B-factor index (LBI), a novel computational metric for prioritizing protein-ligand complexes for docking.
View Article and Find Full Text PDFNeotrop Entomol
September 2025
Dept of Zoology, Government College Univ Lahore, Lahore, Pakistan.
The control of dengue vector mosquitoes by utilizing plant-based eco-friendly larvicides is pivotal in suppressing the spread of dengue with minimum environmental toxicity. This study aimed to evaluate the larvicidal activity of nanoliposomes containing p-cresol and Myristica fragrans Houtt. essential oil (EO) against Aedes aegypti L.
View Article and Find Full Text PDFActa Pharmacol Sin
September 2025
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Non-small cell lung cancer (NSCLC) is an aggressive malignancy with a poor prognosis. Abnormal expression of focal adhesion kinase (FAK) is closely linked to NSCLC progression, highlighting the need for effective FAK inhibitors in NSCLC treatment. In this study we conducted high-throughput virtual screening combined with cellular assays to identify potential FAK inhibitors for NSCLC treatment.
View Article and Find Full Text PDFUrol Oncol
September 2025
Nutritional, Genes and Human Disease Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh. Electronic address:
Background: Understanding the mutational landscape is critical for elucidating the molecular mechanisms driving cancer progression. This study aimed to profile somatic mutations in bladder cancer patients (N=7) from Bangladesh to provide insights into the genetic alterations underlying this malignancy.
Methods: We performed targeted sequencing of 50 oncogenes and tumor suppressor genes using the Ion AmpliSeq Cancer Hotspot Panel v2 on tumor and matched blood samples from seven bladder cancer patients.