Synthesis of novel hydrazide Schiff bases with anti-diabetic and anti-hyperlipidemic effects: in-vitro , in-vivo and in-silico approaches

Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 12

Published: March 27, 2024

The increasing global incidence of non-insulin-dependent diabetes mellitus (NIDDM) necessitates innovative therapeutic solutions. This study focuses on the design, synthesis and biological evaluation Schiff base derivatives from 2-bromo-2-(2-chlorophenyl) acetic acid, particularly hydrazone compounds 4a 4b. Both in-vitro in-vivo assays demonstrate these derivatives' strong antidiabetic anti-hyperlipidemic properties. In a 15-d experiment, we administered 4b at doses 2.5 5 mg/kg body weight, which effectively improved symptoms alloxan-induced in mice. These included weight loss, increased water consumption high blood glucose levels. also normalized abnormal levels total cholesterol (TC), triacylglycerol (TG) low-density lipoprotein (LDL-C), while raising high-density (HDLC). Computational analysis showed that inhibited α-glucosidase enzyme by interacting with key catalytic residues, specifically Asp214 Asp349. computational results were confirmed through tests, where inhibitory activity, IC50 values 0.70 ± 0.11 10.29 0.30 µM, respectively. more effective than standard drug, acarbose, had an value 873.34 1.67 µM. Mechanistic studies further indicated competitive inhibition, reinforcing potential for NIDDM treatment.

Language: Английский

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Flurbiprofen Clubbed Schiff's Base Derivatives as Potent Anticancer Agents: In Vitro and In Silico Approach towards Breast Cancer

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1321, P. 139743 - 139743

Published: Aug. 29, 2024

Language: Английский

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Synthesis and characterization of some novel benzoyl thioureas as potent α-glucosidase inhibitors: In vitro and in silico

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1308, P. 138133 - 138133

Published: March 22, 2024

Language: Английский

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3-Acetyl-11-keto-β-boswellic Acid-Based Hybrids Alleviate Acetaminophen-Induced Hepatotoxicity in HepG2 by the Regulation of Inflammatory and Oxidative Stress Pathways: An Integrated Approach

ACS Omega, Journal Year: 2023, Volume and Issue: 8(42), P. 39490 - 39510

Published: Oct. 12, 2023

In an effort to develop new compounds for managing drug-induced liver injury, we prepared 23 novel hybrids based on 3-acetyl-11-keto-β-boswellic acid (AKBA) using various biocompatible linkers. A bioguided approach was employed identify the most promising hybrid. Eight exhibited superior anti-inflammatory activity compared parent compound. Two of these (5b and 18) were able reduce gene expression TNF-α in LPS-induced inflammation RAW 264.7 cells, similar dexamethasone. Subsequently, hepatoprotective potential evaluated against acetaminophen (APAP) toxicity HepG2 cells at doses 1 10 μM. Both effectively restored cytokine levels, which had been elevated by APAP, normal levels. Furthermore, they normalized depleted superoxide dismutase reduced glutathione levels while significantly reducing malondialdehyde (MDA) Network pharmacology analysis suggested that AKBA-based exert their action regulating PI3K EGFR pathways, activating mechanisms, initiating tissue repair regeneration. Molecular docking studies provided insights into interaction with PI3K. Additionally, demonstrated good stability different pH following first-order kinetics, relatively long half-lives, suggesting absorption circulation without significant degradation.

Language: Английский

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The anti‐breast cancer therapeutic potential of 1,2,3‐triazole‐containing hybrids

Archiv der Pharmazie, Journal Year: 2023, Volume and Issue: 357(3)

Published: Dec. 18, 2023

Abstract Breast cancer, as one of the most common invasive malignancies and leading cause cancer‐related deaths in women globally, poses a significant challenge world health system. Substantial advances diagnosis treatment have significantly improved survival rate breast cancer patients, but number incidences are projected to increase by 40% 50%, respectively, 2040. Chemotherapy is principal treatments for therapy, multidrug resistance severe side effects remain major obstacles success treatment. Hence, there vital need develop novel chemotherapeutic agents combat this deadly disease. 1,2,3‐Triazole, which can be effectively constructed click chemistry, not only serve linker connect different anti‐breast pharmacophores also valuable pharmacophore with potential favorable properties such hydrogen bonding, moderate dipole moment, enhanced water solubility. Particularly, 1,2,3‐triazole‐containing hybrids demonstrated promising vitro vivo against both drug‐sensitive drug‐resistant forms possessed excellent selectivity targeting biological pathways associated representing privileged scaffolds discovery candidates. This review concentrates on latest advancements potential, including work published between 2020 present. The structure–activity relationships (SARs) mechanisms action reviewed shed light development more effective multitargeted

Language: Английский

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New 1H-1,2,3-Triazole Analogues of Boswellic Acid are Potential Anti-Breast Cancer Agents

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1319, P. 139447 - 139447

Published: July 26, 2024

Language: Английский

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Eriocitrin Disrupts Erythrocyte Membrane Asymmetry through Oxidative Stress and Calcium Signaling and the Activation of Casein Kinase 1α and Rac1 GTPase

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(12), P. 1681 - 1681

Published: Dec. 2, 2023

Hemolysis and eryptosis result in the premature elimination of circulating erythrocytes thus contribute to chemotherapy-related anemia, which is extremely prevalent cancer patients. Eriocitrin (ERN), a flavanone glycoside citrus fruits, has shown great promise as an anticancer agent, but potential toxicity ERN human remains unstudied.Erythrocytes were exposed concentrations (10-100 μM) for 24 h at 37 °C, hemolysis associated markers quantified using colorimetric assays. Eryptosis was assessed by flow cytometric analysis detect phosphatidylserine (PS) exposure annexin-V-FITC, intracellular Ca2+ Fluo4/AM, oxidative stress with 2-,7-dichlorodihydrofluorescin diacetate (H2DCFDA). also tested against specific signaling inhibitors anti-hemolytic agents.ERN caused significant, concentration-dependent 20-100 μM. significantly increased percentage eryptotic cells characterized elevation stress. Furthermore, hemolytic activity ameliorated presence D4476, NSC23766, isosmotic urea sucrose, polyethylene glycol 8000 (PEG). In whole blood, elevated MCV ESR, no appreciable effects on other peripheral blood cells.ERN promotes erythrocyte death through PS externalization, accumulation, membrane blebbing, loss cellular volume, These toxic effects, mediated casein kinase 1α Rac1 GTPase, can be urea, PEG. Altogether, these novel findings are relevant further development therapeutic.

Language: Английский

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Triterpenoids from Frankincense and Boswellia: A Focus on their Pharmacology and 13C-NMR Assignments

Phytochemistry, Journal Year: 2024, Volume and Issue: 229, P. 114297 - 114297

Published: Oct. 12, 2024

Language: Английский

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Formulation development, characterization, and evaluation of sorafenib-loaded PLGA–chitosan nanoparticles

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 9, 2024

The basic purpose of this work was to develop environmentally friendly, biodegradable, and biocompatible polymeric nanoparticles sorafenib that can effectively release the desired drug in a customized controlled manner for targeting hepatocellular carcinoma. solvent evaporation technique employed synthesis sorafenib-loaded PLGA–chitosan nanoparticles, followed by various experimental specifications compatibility studies using poloxamer 407 as stabilizer. best thus synthesized were selected be used cytotoxicity investigations through vitro vivo assessments. For tests, dialysis bag diffusion used. both chitosan PLGA loaded with sorafenib, biphasic pattern found, exhibiting protracted lasting 10 days after 24-h burst release. As animals, rabbits utilized evaluate different pharmacokinetic properties formulations. Plasma samples extracted acetonitrile analyzed developed HPLC method. Pharmacokinetic parameters such AUC 0-t , C max MRT, Vd, half-life (t 1/2 ) enhanced significantly ( p ≤ 0.001), while clearance considerably decreased 0.001) chosen contrast commercially accessible formulation (Nexavar ® ). reference calculated performing an MTT assay against HepG2 cell lines. nanoformulations possess appropriate physicochemical properties, better targeting, surface morphology, prolonged kinetics. improved when results compared available

Language: Английский

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