Objective: This study aimed to investigate ten polyphenolic phytochemicals derived from Mangifera indica as potential alternatives to combat S. stercoralis.

Methods: The efficacy of these compounds was evaluated using computational techniques, including density functional theory (DFT) analysis, molecular docking, adsorption, distribution, metabolism, excretion, and toxicity (ADMET) assessment, and molecular dynamics (MD) simulations.

Results: DFT calculations revealed significant chemical reactivity in compounds such as kaempferol, ellagic acid, quercetin, norathyriol, mangiferin, and ferulic acid. Molecular docking identified mangiferin, quercetin, kaempferol, and norathyriol as top candidates for targeting key proteins (DAF-12) linked to S. stercoralis infection. A 200-ns MD simulation of the proteinligand complex demonstrated the stability and binding behavior of these compounds compared to the reference drug, thiabendazole. ADMET screening confirmed their drug-likeness. Notably, quercetin and mangiferin exhibited strong binding affinities (ΔGbind = -42.35 and -54.57 kcal/mol, respectively), outperforming thiabendazole (ΔGbind = -28.94 kcal/mol).

Conclusion: Quercetin and mangiferin emerge as promising alternatives to thiabendazole, offering favorable chemical reactivity, potent inhibition constants, and strong biological activity for the treatment of S. stercoralis.]]> https://www.benthamscience.com/article/1475082026-04-10 Introduction: Our group previously reported isatin-based hydrazones (ISB1-ISB6) were further evaluated for their in vitro acetylcholine esterase, butylcholinestrase and cytotoxic effects on cancer cell lines. The compounds successfully suppressed AChE and BChE, with Ki values ranging from 1.06±0.07 to 23.57±1.64 nM for AChE and 15.31±1.28 to 84.41±8.04 nM for BChE. However, the IC50 values of these compounds for AChE and BChE were found to be in the ranges of 1.45-25.51 nM and 16.38-92.90 nM, respectively.

Method: Furthermore, to explore the anti-tumor potential of our newly synthesized compounds, we conducted a cytotoxic MTT assay to assess their impact on two different cancer cell lines: MCF7 and A2780.

Results: Our findings highlight diverse cytotoxic profiles among the compounds. Specifically, ISB2, ISB3, and ISB4 demonstrated potential cytotoxicity in the A2780 cell line, while ISB6 exhibited significant cytotoxicity in the MCF7 cell line. This suggests that these compounds have different effects on cancer cell types, indicating the need for further investigation into their potential applications in cancer therapy.

Conclusion: Finally, molecular docking and dynamic study revealed that lead molecule ISB3 provides stability in the AChE and BChE protein-ligand complex.]]> https://www.benthamscience.com/article/1479752026-04-10 Background: XueFuZhuYu pills (XFZY), a traditional Chinese herbal formula originated from the xuefuzhuyu decoction in Correction on Errors in Medical Classics, has a certain clinical effect on the treatment of hyperprolactinemia (HPRL) caused by antipsychotics. However, the active ingredients and mechanism by which XFZY contributes to the hyperprolactinemia caused by antipsychotics remain unclear.

Objectives: The aim of the study was to investigate the molecular basis of XFZY in the therapy of antipsychotic-induced HPRL and to establish a scientific foundation for its application.

Methods: First, the UHPLC-Q-TOF-MS/MS methodology was employed to perform chromatographic separation and gather mass spectrometry data. Subsequently, the preprocessed mass spectrometry data were uploaded to the Global Natural Products Social Molecular Networking (GNPS) platform for spectral library interrogation and molecular network analysis. Next, based on the detected chemical constituents and the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the effective chemical components within XFZY were chosen. Swiss Target Prediction was employed to determine probable targets of components, and we used Cytoscape to create a network of components and their associated targets. After that, HPRL-related targets were found and filtered using four disease databases, and then a proteinprotein interaction (PPI) network was built using the STRING database. Cytoscape was utilized to conduct visualization and cluster analysis. Meanwhile, the Metascape database was adopted for the enrichment analysis of GO and KEGG. At last, Autodock Vina was applied to perform molecular docking between the principal components and target proteins.

Results: In total, 213 compounds were discovered in XFZY. Two hundred eight active chemical components, 622 probable targets, and 242 HPRL-related target genes were identified. There were 76 common targets between the XFZY and HPRL. Following analysis, 1371 GO biological process items and 162 KEGG signal pathways were identified. The primary chemicals and target proteins exhibited great affinity in molecular docking.

Conclusion: This research manifests that XFZY, as a traditional Chinese medicine formula, proffers a novel pathway for the treatment of antipsychotic-induced HPRL. We elucidated the specific molecular mechanisms underlying the anti-HPRL effects of XFZY and its active ingredients, laying a foundation for the subsequent clinical applications of this formula.]]> https://www.benthamscience.com/article/1482712026-04-10 Background: Chemotherapy remains a primary treatment for stopping cancer cell growth. Unfortunately, resistance to chemotherapy is a challenge that leads to cancer relapse. Overexpression of the antiapoptotic proteins is a major cause of this resistance. BH3 mimetic compounds were developed in this work to deal with this issue by blocking the Bcl-2 antiapoptotic proteins. Currently, only a few BH3 mimetics are approved drugs, and even fewer can effectively target all antiapoptotic Bcl-2 proteins.

Objective: The present study aimed to explore and screen the prodiginine family of molecules for new potential and effective BH-3 mimetics.

Methods: Molecular docking and molecular dynamics (MD) simulations were used to assess the potential of 30 prodiginine analogs as BH3 mimetics, including the obatoclax molecule, a prodiginine member used in clinical trials as a BH3 mimetic.

Results: Molecular docking results showed four prodiginines to have lower free binding energy values for five Bcl-2 proteins (Bcl-2, Mcl-1, Bcl-w, Bcl-xl, and Bfl1) compared to the reference drug, obatoclax. The five analogs presented safe pharmacological profiles according to Lipinski’s rule of five. Furthermore, MD simulations demonstrated butylcycloheptyl prodiginine- Bcl-2 and prodigiosin-R2-Bcl-xl complexes to be more stable than the reference complexes obatoclax-Bcl-2 and obatoclax-Bcl-xl.

Conclusion: Based on these results, butylcycloheptyl prodigiosin and prodigiosin-R2 could be more effective BH3 mimetics and should be further studied.]]> https://www.benthamscience.com/article/1478512026-04-10 Background: Oral Squamous Cell Carcinoma (OSCC) is a multiple-phase carcinogenic disease that concurrently involves malignant lesions, invasion, and metastasis. It has been reported that Ubiquitin-conjugating enzymes play a significant role in the progression of OSCC and other fatal cancers through the process of ubiquitination. Among them, UBE2D1 represents a promising target for therapeutic intervention. Strategies aimed at inhibiting UBE2D1 could restore the function of tumor suppressors, such as p53, and potentially enhance the effectiveness of existing cancer therapies.

Objective: This study aims to discover the potential natural inhibitors of UBE2D1 from an extensive chemical library through computational techniques.

Methods: This study utilized in silico methods, such as virtual screening, molecular docking, analysis of pharmacokinetic parameters, and molecular dynamics simulation, to discover the most effective inhibitors for the ubiquitin-conjugating enzyme.

Results: Based on binding affinity, the top six compounds, ZINC15113777, ZINC225461658, ZINC107430641, ZINC259440, ZINC4025306, and ZINC107283931, were found to be the best for the selected target. Also, molecular dynamic simulation results showed that all these compounds form stable complexes with UBE2D1.

Conclusion: Based on our analysis of the results, we have determined that natural products, specifically ZINC15113777, ZINC4025306, and ZINC107283931, have the ability to inhibit UBE2D1 efficiently and could be utilized as potential drugs for the treatment of OSCC and other cancers. Such approaches may help to reinstate normal apoptotic pathways and improve overall treatment outcomes in patients with cancers characterized by UBE2D1 dysregulation. Additionally, conducting in-vitro/vivo studies on these molecules could be a prospective avenue in the realm of pharmaceutical research.]]>