Bioorganic & Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: unknown, P. 130086 - 130086
Published: Dec. 1, 2024
Language: Английский
Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 17(4), P. 449 - 465
Published: Jan. 31, 2025
The study of chalcone-1,2,3-triazole hybrids for anticancer activity is quite a recent area focus, primarily because the increasing demand developing new drugs to treat cancer. chalcones and 1,2,3-triazole rings in hybrid compounds has recently emerged as promising strategy novel agents. ring, known its stability hydrogen bonding capabilities, enhances target binding affinity these hybrids. Chalcones possess an α,β-unsaturated carbonyl system crucial their synergistic effect two moieties results with potent properties. This review explores structure-activity relationship studies which revealed that electronic lipophilic properties substituents on phenyl significantly influence activity. Electron-donating electron-withdrawing groups can affect cellular uptake engagement. Incorporating various into ring improve selectivity potency against specific cancer cell lines. These often exert effects through apoptosis cycle disruption. Recent research indicates chalcone hold therapeutic promise Further optimization SAR in-depth mechanistic investigations could lead development highly selective agents minimal toxicity.
Language: Английский
Citations
0
Pharmacology Research & Perspectives, Journal Year: 2025, Volume and Issue: 13(2)
Published: April 1, 2025
ABSTRACT Huntington's disease (HD) is a challenging neurodegenerative disorder linked to Huntingtin ( HTT ) gene mutation, lacking an effective cure despite numerous therapeutic attempts. Cordyceps sinensis , recognized for its health benefits, particularly constituent cordycepin, exhibits neuroprotective effects in various diseases. However, the potential of cordycepin HD remains insufficiently explored. In this study, vitro experiments using cell models demonstrate that treatment enhances survival, slightly diminishes mutant aggregates, and improves neuronal formation. vivo investigations on R6/2 transgenic mice reveal modest increase body weight slight amelioration pathological aggregates following administration, although behavioral changes are not significant. While underlying mechanisms remain unexplored, findings suggest cordycepin's promise as supplementary HD, providing reducing protein aggregates.
Language: Английский
Citations
0
Journal of physiological investigation., Journal Year: 2025, Volume and Issue: unknown
Published: April 14, 2025
Abstract Cerebral ischemia-reperfusion (CIR) injury results in significant secondary brain damage after ischemic stroke due to oxidative stress, mitochondrial dysfunction, and neuroinflammation. Transchalcone (TCH), a polyphenolic compound, exhibits antioxidant anti-inflammatory properties that may contribute neuroprotection. The present study investigated the potential protective effects of TCH rat model CIR, focusing on its impact activation AMP-activated protein kinase (AMPK) pathway, function, inflammatory mediators. Sixty adult Sprague–Dawley rats were randomly divided into five groups Control, CIR (ischemia-reperfusion only), CIR+TCH (CIR with TCH), CIR+CC compound C), CIR+CC+TCH C plus TCH). (100 μg/kg b.w per day) was given intraperitoneally over 7 days before animals. Middle cerebral artery occlusion performed for 60 min induce ischemia, then blood flow restored (reperfusion) 24 h. Neuromotor function assessed using neurological scoring, rotarod, grid tests. infarct volumes determined 2,3,5-triphenyltetrazolium chloride staining. Mitochondrial evaluated fluorometric calorimetric methods. Oxidative stress mediators measured by enzyme-linked immunosorbent assay. Protein expression analyzed Western blotting. significantly impaired neuromotor increased volume, elevated reactive oxygen species (ROS) levels, disrupted adenosine triphosphate (ATP) synthesis manganese superoxide dismutase (Mn-SOD) activity. It also heightened pro-inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-alpha, nuclear factor kappa B levels while reducing IL-10 level. treatment attenuated outcomes promoting AMPK phosphorylation, upregulating peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) erythroid 2-related 2 (NRF2) expression, ROS, improving ATP production Mn-SOD activity, suppressing cytokine increasing IL-10. Co-treatment (a selective inhibitor) diminished TCH, confirming contribution signaling neuroprotective mechanism. provides neuroprotection against activating AMPK/PGC-1α AMPK/NRF2 signaling, preserving modulating inflammation. These findings highlight therapeutic management.
Language: Английский
Citations
0
Journal of physiological investigation., Journal Year: 2024, Volume and Issue: 67(6), P. 312 - 320
Published: Nov. 1, 2024
Abstract Parkinson’s disease (PD) is a gradually worsening neurodegenerative condition marked by the deterioration of dopaminergic neurons, motor dysfunction, and mitochondrial dysfunction. Trans-chalcone, natural flavonoid, has shown promise in various models because its antioxidant anti-inflammatory features. This study investigates neuroprotective effects transchalcone rat model PD, focusing on impact activation levels AMP-activated protein kinase (AMPK) signaling pathway, sirtuin1 (SIRT1) peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) proteins, mitochondrial-inflammatory responses. Male Sprague Dawley rats were allocated into five groups Control, Control plus transchalcone, PD compound-C, Compound-C trans-chalcone. was induced using intranigral 6-hydroxydopamine injection. Trans-chalcone (100 μg/kg) compound-C (20 mg/kg) intraperitoneally administered daily for 4 weeks rats. Motor function assessed rota-rod grid tests. Striatal dopamine cytokines (interleukin 1-beta [IL-1 β], IL-10) p65-nuclear factor kappa-B (NF-κB) measured with enzyme-linked immunosorbent assay. Mitochondrial evaluated fluorometric techniques. The expression phosphorylated AMPK, PGC-1α, SIRT1 analyzed Western blotting. treatment significantly improved function, evidenced increased latency to fall test recovered traversal time test. It also restored levels, enhanced (reduced reactive oxygen species membrane potential, adenosine triphosphate production), normalized (IL-1 β, p65-NF-κB, upregulated proteins PD. Inhibition AMPK activity suppressed impacts trans-chalcone, highlighting contribution pathway mechanism action. Neuroprotective mitoprotective trans-chalcone mostly mediated through AMPK-SIRT1-PGC1α pathway. These results indicate that could be promising therapeutic agent warranting further investigation assess efficacy safety human patients.
Language: Английский
Citations
2
Brazilian Journal of Science, Journal Year: 2024, Volume and Issue: 3(11), P. 1 - 15
Published: Oct. 10, 2024
For several years, different drugs have been used to treat heart failure, such as digoxin, captopril, spironolactone, milrinone, levosimedam, dobutamine, and others. However, some of these can produce secondary effects arrhythmia, cough, hyperkalemia, Analyzing data, this study aimed evaluate the interaction chalcone derivatives (1-17) with calcium channels using theoretical models. It is important mention that 7pjx protein, nifedipine, amlodipine, diltiazem, verapamil were tools in DockingServer program. The results showed differences compared drugs. Other data indicate inhibition constant (Ki) for analog 1 was lower verapamil, diltiazem. Besides, other suggest Ki compound 11 All could act channel inhibitors; phenomenon be translated into changes blood pressure through a decrease intracellular levels. These good therapeutic alternatives failure.
Language: Английский
Citations
0
Bioorganic & Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: unknown, P. 130086 - 130086
Published: Dec. 1, 2024
Language: Английский
Citations
0