In-silico study of active phytochemicals and molecular mechanism of Hydrocotyle javanica Thunb.in treating MDR enterobacterial infection

IN SILICO ANALYSIS OF ANTIFUNGAL POTENTIAL OF Centella asiatica ACTIVE COMPOUNDS AS NATURAL BIOFUNGICIDES FOR OIL PALM FUNGAL DISEASE CONTROL

This study aimed to analyze the potential of active compounds in pegagan (Centella asiatica) as natural antifungal agents using an in silico approach with PASS Online, SwissADME, and pkCSM. The PASS Online analysis showed that most active compounds of pegagan had antifungal activity probability (Pa) values above 0.5, indicating relatively high biological potential. The compounds with the highest activity were 3-O-beta-D-Glucopyranosyl sitosterol (0.722), Centellin (0.715), Centellicin (0.655), Asiatic acid (0.651), and Kaempferol (0.651). Triterpenoid, flavonoid, and sesquiterpene compounds are known to act through mechanisms including disruption of the fungal cell membrane, inhibition of cell wall synthesis, interference with energy metabolism, and enhancement of oxidative stress in pathogenic cells. SwissADME analysis indicated that the majority of compounds exhibited good solubility, moderate lipophilicity, and bioavailability scores consistent with biological activity. Acetylursolic acid showed the highest bioavailability score of 0.85, while most other compounds ranged between 0.55 and 0.56. The drug-likeness results demonstrated that most compounds complied with Lipinski, Veber, and Muegge rules, indicating their potential as bioactive antifungal candidates. Physicochemical property analysis revealed TPSA values, hydrogen-bond donors and acceptors, and molecular flexibility that support membrane penetration and interactions with fungal biological targets. In addition, pkCSM results showed that most compounds were non-mutagenic, non-hepatotoxic, and exhibited relatively low environmental toxicity. Overall, the results suggest that pegagan has strong potential as a source of environmentally friendly natural antifungal compounds and may be further developed as a biofungicide for controlling fungal diseases in oil palm plants.

Studi In Silico Senyawa Bioaktif Ekstrak Curcuma longa sebagai Inhibitor Protein LASR pada Bakteri Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogenic bacterium that employs a quorum-sensing mechanism mediated by the LasR protein to regulate biofilm formation and virulence. This study aims to analyze the potential of bioactive compounds from Curcuma longa as inhibitors of the LasR protein through an in silico approach. The study employed a computational approach using molecular docking to predict interactions between the ligands and the LasR protein. The analysis was followed by the prediction of physicochemical properties based on Lipinski’s Rule of Five and the evaluation of pharmacokinetic and toxicity profiles using ADMET parameters. The molecular docking results showed that all compounds had negative docking scores ranging from −6.9297 to −9.5288 kcal/mol. Curcumin and demethoxycurcumin exhibited the strongest binding affinities, with docking scores of −9.5288 and −9.5189 kcal/mol, respectively. All compounds met the criteria of Lipinski’s Rule of Five and demonstrated reasonably favorable ADMET profiles, although a moderate potential for toxicity was identified based on the AMES mutagenicity and human hepatotoxicity parameters. This study concludes that the bioactive compounds of Curcuma longa, particularly curcumin and demethoxycurcumin, have the potential to be developed as candidate inhibitors of the LasR protein. These findings provide a computational basis for compound structure optimization and further research through in vitro and in vivo testing to validate their effectiveness and safety as LasR inhibitors.

Integrated Phytochemical Profiling and Computational Evaluation of Psidium Guajava L. Leaves as A Potential Source of Antimalarial Therapeutics

The escalating prevalence of malaria, coupled with the rapid emergence of multidrug-resistant Plasmodium strains, necessitates the urgent discovery of novel, sustainable, and affordable antimalarial agents. Psidium guajava L. (guava) has long been utilized in traditional medicine across tropical regions for managing febrile illnesses; however, a comprehensive scientific validation of its phytochemical synergy and molecular mechanisms remains imperative. This study investigates the phytochemical landscape of Psidium guajava leaves using High Performance Liquid Chromatography (HPLC) and evaluates its therapeutic potential through an integrated computational framework. HPLC analysis revealed a diverse profile of 15 bioactive compounds, with Quercetin (53.08%, 0.5308 mol/L) identified as the predominant constituent, followed by Persin (14.98%) and Zeaxanthine (9.37%). Molecular docking simulations against key Plasmodium falciparum targets, including Dihydrofolate Reductase (PfDHFR) and Lactate Dehydrogenase (PfLDH), demonstrated high binding affinities for Quercetin and its derivatives, suggesting potent inhibitory potential. Furthermore, Density Functional Theory (DFT) calculations at the B3LYP/6-31G(d,p) level elucidated the electronic properties and radical scavenging mechanisms of the primary constituents, highlighting their role in mitigating malaria-induced oxidative stress. These findings provide a rigorous biochemical and computational foundation for the traditional use of P. guajava and position its phytochemicals as promising scaffolds for the development of next-generation antimalarial drugs.

Exploring the Potential of bioactive compounds from Cordyceps sinensis known to infect Lepidoptera larvae as Antimalarial Agents through In silico studies

Malaria has been one of the most prevalent and life-threatening infectious disease worldwide. Despite extensive efforts to control and combat the disease, the emergence of drug resistant malaria parasites have posed a formidable obstacle in the fight against this deadly infection. Insect pathogenic fungi have emerged as a rich and important source of bioactive compounds with diverse pharmacological properties. Consequently, there is need to develop derivatives of bioactive compounds with antimalarial activity from insect pathogenic fungi with improved efficacies and better binding affinities than the existing drugs. Eleven bioactive compounds from insect pathogenic fungi, Cordyceps sinensis that infects larvae of Hepialus (Lepidoptera, ghost moths) were selected from previously reported literature and investigated for their potential antimalarial activity using molecular docking and pharmacokinetic analyses.. These compounds were docked using a model of Triosephosphate isomerase (TPI) protein with Molegro software to identify the compound with the minimum docking score as a design template. Compound 6 (3,5,8-trihydroxy-6-methoxy-2-((1E,3E)-5-oxohexa-1,3-dien-1-yl)naphthalene-1,4-dione) with the lowest moldock score (-112.711 kcal mol-1) was employed as the template. Derivatives were designed by substituting -COOH, -CONH2, -COOCH3, -CN, and -SO3H groups at various positions of the template where three of the designed derivatives had better binding affinities compared to the design template. The docking scores of these designed derivatives were lower than those of the original compounds. Derivative D3 (1,4,6-trihydroxy-3-methoxy-5,8-dioxo-7- ((1E,3E)-5-oxohexa-1,3-dien-1-yl)-5,8-dihydronaphthalene-2-carboxamide) was identified to bind better to the target protein due to its lowest moldock score (-118.325 kcal mol-1). The druglikeness assessment of the designed derivatives demonstrated that all compounds complied with Lipinski’s Rule of Five (Ro5), supporting their favourable drug-like properties and highlighting their potential as promising novel therapeutic candidates for the treatment of malaria.

In silico investigation and identification of potential phytocompounds targeting dengue virus NS5 methyltransferase

Unraveling the Antibacterial Mechanisms of Bletilla striata: A Synergistic Approach Combining Network Pharmacology, Molecular Docking, and In Vitro Validation.

The findings indicate that Bletilla striata exerts antibacterial effects via multi-component, multi-target interactions, particularly with ESR1, EGFR, PTGS2, and MAPK14, particularly with ESR1, EGFR, PTGS2, and MAPK14.