Rheumatoid arthritis (RA) is a prevalent condition characterized by joint inflammation and debilitation. Rheumatoid arthritis affected approximately 18 million individuals worldwide as of 2019, with women constituting approximately 70
Aim: Silent information regulator two homologue one (SIRT1) is an emerging target for managing metabolic disorders. This study aimed to synthesize novel 5-(- substituted phenyl)-2-aryl benzimidazole derivatives and evaluate them for SIRT1 activation. Methods: The compounds were designed according to the findings of the QSAR models framed in our previous studies. Molecular docking and dynamics studies were also performed to explore the interactions of designed compounds with the active site of the SIRT1 enzyme using AutoDock Vina and Schrödinger Maestro version 11.8.012, respectively. Compounds with good binding affinity were synthesized by Suzuki-Miyaura cross-coupling and spectrally characterized. The molecules were evaluated for their in vitro SIRT1 activation properties using a fluorescent screening kit. Based on the results of in vitro assay, a structure-activity relationship was established. SwissADME was employed to calculate the pharmacokinetics characteristics of the synthesized molecules. Results: The molecular docking studies revealed that all the activators were effectively docked in the catalytic active site. All compounds demonstrated interactions with important amino acids like Glu230 and Arg446. In molecular dynamics simulations, the root mean square deviation (RMSD) of compound 5m and protein SIRT1 remained stable, i.e., below 3mm. Compound 5m, 4-(2-(3,4-dihydroxy-5-nitrophenyl)-1H-benzo[d]imidazol- 5-yl)benzaldehyde, was the most potent compound with an EC50 value of 0.006 mM (±0.001) and maximum activation of 240.5%. All the synthesized compounds had acceptable theoretical ADME profiles, and drug-likeness properties complied with Lipinski’s rule. Conclusion: According to the findings, synthesized compounds may be viable leads for SIRT1 activators and may be used to advance preclinical in vivo research utilizing animal models.
Polyphenols are a diverse and widely distributed group of plant-derived phytochemicals known for their broad spectrum of biological activities. Found abundantly in fruits, vegetables, grains, tea, coffee, and wine, these compounds are increasingly recognized for their significant contribution to human health. Their benefits are largely attributed to potent antioxidant, anti-inflammatory, and bioactive properties, which support the prevention and management of chronic diseases. Among their many functions, polyphenols serve as powerful antioxidants, capable of neutralizing reactive oxygen species (ROS) and reducing oxidative stress a key contributor to the development of degenerative diseases such as cancer, cardiovascular conditions, and neurodegenerative disorders including Alzheimer’s and Parkinson’s disease. This review explores the classification of polyphenols based on their chemical structures, their major dietary sources, and their bioavailability and metabolism, which influence their biological efficacy. In addition to their antioxidant potential, polyphenols exhibit a wide range of therapeutic activities, including anti-inflammatory, anti-cancer, cardioprotective, and neuroprotective effects. The review also discusses current challenges in optimizing the health benefits of polyphenols, including limited bioavailability, interactions with other dietary components, and variability in individual metabolism. Finally, future research directions are proposed, emphasizing advanced delivery systems, functional food applications, and integrated clinical studies using tools such as metabolomics and nutrigenomics.
Malaria, caused by Plasmodium parasites and transmitted by Anopheles mosquitoes, remains a significant global health challenge, especially in tropical and subtropical regions where the disease is endemic. The complex Plasmodium lifecycle, involving stages in both the liver and bloodstream, leads to symptoms such as high fever, anemia, and, in severe cases, life-threatening complications, particularly P. falciparum infections. While historical treatments such as quinine and modern therapies such as artemisinin-based combination therapies (ACTs) have been effective, the growing issue of drug and insecticide resistance undermines these efforts. This resistance has spurred the need for new antimalarial drugs and strategies. Among the promising areas of research are heterocyclic compounds, which, due to their diverse and versatile chemical structures, are being investigated for their ability to disrupt the Plasmodium lifecycle. These compounds have potential as novel therapeutic agents that could enhance current treatment options. Understanding the mechanisms underlying drug resistance and advancing these therapeutic innovations are crucial for maintaining effective malaria control and treatment, highlighting the importance of on-going research in this field.
The electronic and magnetic characteristics of TM-doped single-walled SiC nanotubes were studied using Density Functional Theory and the local spin density approximation. From ab initio simulations, bandgap for undoped SiC nanotube and SiC:V systems which are obtained 0.98 eV, and 0.6 (spin-up); 1.4 eV (spin-down), respectively. After doped with 3d transition metals, the SiC nanotube systems induce a magnetic response and the total magnetizations of the quantum confined single walled SiC:Co and SiC:V systems are similar to 1.9 mu(B) and 1.0 mu(B), respectively. The results of total energy calculations predicted that the ferromagnetic and antiferromagnetic phases are stable for VxSi1-xC and CoxSi1-xC. The obtained values of formation energies show the stability of VxSi1-xC and CoxSi1-xC systems. Our results predicted that VxSi1-xC have semi-metallic behavior with Curie temperature is nearly above to 300 K and it suitable for spin-based applications in future material informatics research field. CoxSi1-xC shows metallic behavior, and it is the better choice for optoelectronics devices with a Curie temperature less than room temperature.
