Currently, the rise and dissemination of resistance to antimalarial drugs pose a significant global challenge. There is an ongoing effort to discover novel compounds for the development of new antimalarial therapies. This study aimed to evaluate harmicine derivatives known for their antimalarial activity and to explore their potential interactions with Plasmodium falciparum, specifically targeting the crucial falcipain-2 enzyme in the parasite's life cycle. Molecular docking and dynamics studies showed that compound 6f interacted with the binding site of the enzyme and stayed stable for 100 ns, the best of the derivatives. It had a binding affinity score of -8.4, higher than chloroquine (-5.5). This means that it might be better than chloroquine at inhibiting falcipain-2. Additionally, compound 6f successfully passed Lipinski's Rule of Five, suggesting its potential for oral use. Researchers found that the results of this study could help make new, stronger Harmicines with better antiplasmodial activities. This could lead to the creation of very effective medicines that fight malaria
Dental caries, caused primarily by Streptococcus mutans, is a major oral health issue worldwide. Sortase A (SrtA), a transpeptidase enzyme, plays a key role in bacterial adhesion and colonization, making it a potential target for caries prevention. This study aims to investigate the antibacterial potential of beluntas leaf (Pluchea indica) metabolites against S. mutans through in silico analysis. Using molecular docking and molecular dynamics (MD) simulations, we analyzed the binding interactions between beluntas leaf metabolites and SrtA. The results showed that beta-stigmasterol exhibited the strongest binding affinity to SrtA, with a binding energy of -8.73 kcal/mol. Molecular dynamics simulations further confirmed the stability of the beta-stigmasterol-SrtA complex. Furthermore, binding free energy analysis using MMPBSA showed that stigmasterol exhibited a significantly stronger binding affinity to Sortase A (−131.86 ± 12.57 kJ/mol) compared to astilbin (−54.38 ± 18.47 kJ/mol), supporting its potential as a potent anti-caries agent. This study suggests that beluntas leaf metabolites, particularly beta-stigmasterol, could be a promising natural agent for preventing dental caries by targeting the SortA receptor.
Diabetes Mellitus (DM) is a metabolic disorder marked by hyperglycemia, often necessitating alternatives to long-term medications due to side effects. This study evaluates the antioxidant and anti-diabetic potential of white frangipani (Plumeria acuminata L.) and red frangipani (Plumeria rubra L.) extracts. In alloxan-induced diabetic mice, a combination of white frangipani extract (WFE) 200 mg/kgBW and red frangipani extract (RFE) 400 mg/kgBW reduced blood glucose by 57.7%, while a dose of WFE 400 mg/kgBW and RFE 400 mg/kgBW in the OGTT method resulted in a 71.3% reduction. The extracts significantly reduced glucose levels compared to the Negative Control, with no significant difference from the Positive Control group (p>0.05). In silico_docking analysis revealed that Plumericin, a major metabolite, had high binding affinity to the SGLT-2 receptor (-9.36 kcal/mol), close to the native ligand (-11.46 kcal/mol). Molecular dynamics simulations confirmed the Plumericin-SGLT-2 complex's stability, supporting the therapeutic potential of these extracts for DM treatment. This dual In vivo and in silico approach provides a comprehensive understanding of their therapeutic potential and supports further exploration of these extracts as candidates for diabetes treatment
The global health crisis precipitated by COVID-19, caused by severe acute respiratory syndrome-Coronavirus 2 (SARS-CoV-2), has spurred an urgent quest for effective therapeutic interventions. Several repurposed drugs, including chloroquine, hydroxychloroquine, ivermectin, artemisinin, remdesivir, and azithromycin, have been explored for their antiviral potential. Amid this pharmacological landscape, curcumin—a natural polyphenolic compound renowned for its broad-spectrum bioactivity—has emerged as a promising candidate in the fight against COVID-19. Recent investigations into curcumin analogues and derivatives further underscore its therapeutic versatility. This study seeks to unravel the molecular interactions of hypothetical azo curcumins and hydroxychloroquine with the SARS-CoV-2 main protease, employing molecular docking and computational analysis to elucidate their binding affinities and mechanistic insights. By leveraging advanced computational techniques, this research endeavours to provide a deeper understanding of these molecules' antiviral potential, paving the way for future pharmacological developments in combating SARS-CoV-2.
The determination of redox potential (E°) was performed by computational study with correlation- function of B3LYP, for (Cu-L1), (Cu-L2), (Cu-L3) and (Cu-L4) were performed with the help of density functional theory (DFT). The basis set of def2-SVP def2/J D3BJ was used for geometry optimization and frequency calculation. The results showed that the calculation of redox potential of Cu-Ligand complexes were around E° of 0.82 to 0.970 V (vs NHE) and the calculated VOC values for the designed Cu-Ligand complexes range from 1.32 to 1.47 vs NHE (V). Increasing VOC can leads to higher JSC values, the largest VOC values were occupied by Cu-L1 which had the highest reduction potential (0.970 V vs. NHE). The complexes are promising to be used as a redox couple on DSSC’s application due to Voc and Regeneration value consideration.
