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Escherichia coli (E. coli), a common human gut bacterium, is generally harmless but capable of causing infections and contributing to diseases like urinary tract infections, sepsis/meningitis, or diarrheal diseases. Notably, E. coli is implicated in developing gallbladder cancer (GBC) either through ascending infection from the gastrointestinal tract or via hematogenous spread. Certain E. coli strains are known to produce toxins, such as cytolethal distending toxins (CDTs), that directly contribute to the genetic mutations and cellular abnormalities observed in GBC. Broccoli (Brassica oleracea) is known for its health-promoting properties, including antimicrobial, antioxidant, and immunomodulatory effects, and is rich in essential compounds. Our study investigates the potential of the phytochemicals of B. oleracea to inhibit the CdtB (PDB ID: 2F1N) protein of E. coli which plays a significant role in the pathogenesis of GBC. By employing in silico molecular docking, Glucosinolates and Indole-3-carbinol emerged as promising inhibitors, demonstrating strong bonding affinities of -8.95 and − 8.5 Kcal/mol, respectively. The molecular dynamic simulation showed that both compounds maintained stable interaction with CdtB with minimal conformational changes observed in the protein-ligand complexes. Additionally, the ADMET analysis provided evidence for the drug-likeness properties of the lead compounds. Furthermore, the DFT (Density Functional Theory) revealed that Indole-3-carbinol is more chemically stable but less reactive than Glucosinolates, with HOMO-LUMO gaps of 5.14 eV and 4.50 eV, respectively. Finally, the in vitro antibacterial assessment confirmed the inhibitory effect of Glucosinolates and Indole-3-carbinol against E. coli through disc diffusion assay with the zone of inhibition 34.25 ± 0.541 and 28.67 ± 0.376 mm compared to the control ciprofloxacin. Our study provides crucial data for developing novel therapeutic agents targeting E. coli-associated GBC from the phytochemicals of B. oleracea. [ABSTRACT FROM AUTHOR]

Lasia spinosa (L. spinosa) is widely used in Asian countries for treating various diseases and as a vegetable, yet its bioactive properties remain under-researched. It is traditionally utilized in Ayurveda and the AYUSH system of medicine for its medicinal properties, and commonly used to treat digestive disorders, respiratory issues, and inflammatory conditions. This study aims to identify the phytochemicals in L. spinosa leaves and fruit extracts and evaluate their biological activities. Phytochemicals in methanol extracts of L. spinosa fruits and leaves were identified by GC-MS analysis. Antioxidant and cytotoxic activities were assessed using the DPPH free radical and nitric oxide (NO) scavenging assay and brine shrimp lethality test. Antibacterial activity was evaluated against Shigella boydii, Shigella flexneri, Streptococcus iniae, and Streptococcus dysgalactiae, while antifungal properties were tested against Cercospora beticola and Rhizoctonia solani. Molecular docking was conducted to predict the effectiveness of L. spinosa phytochemicals against NADPH oxidase and the Shigella effector OspG. Nine compounds were detected from both extracts. The methanol leaves extract exhibited superior antioxidant activity compared to the fruit extract, with IC50 values of 111.81 ± 8.99 µg/ml and 174.81 ± 4.86 µg/ml, respectively, as determined by the DPPH scavenging assay. The nitric oxide (NO) scavenging assay also revealed higher potency in the leaves extract (IC50 = 138.59 ± 1.50 µg/ml) compared to the fruit extract (IC50 = 196.47 ± 1.72 µg/ml). Both extracts showed significant antimicrobial activity against all tested microorganisms. In silico studies indicated notable inhibitory activity of all phytochemicals against the target proteins, with Linoelaidic acid and 9-Octadecenamide, (Z)- exhibiting the highest activity against NADPH oxidase (PDB: 2cdu) and Shigella flexneri OspG effector kinase (PDB: 4bvu), respectively. These findings suggest that L. spinosa has potent antioxidant and antimicrobial activities. Compounds from this plant could serve as lead compounds for developing antioxidant and antibacterial agents. However, molecular studies should be addressed. [ABSTRACT FROM AUTHOR]

The pharmacological effects of limonene, especially their derivatives, are currently at the forefront of research for drug development and discovery as well and structure-based drug design using huge chemical libraries are already widespread in the early stages of therapeutic and drug development. Here, various limonene derivatives are studied computationally for their potential utilization against the capsid protein of Herpes Simplex Virus-1. Firstly, limonene derivatives were designed by structural modification followed by conducting a molecular docking experiment against the capsid protein of Herpes Simplex Virus-1. In this research, the obtained molecular docking score exhibited better efficiency against the capsid protein of Herpes Simplex Virus-1 and hence we conducted further in silico investigation including molecular dynamic simulation, quantum calculation, and ADMET analysis. Molecular docking experiment has documented that Ligands 02 and 03 had much better binding affinities (− 7.4 kcal/mol and − 7.1 kcal/mol) to capsid protein of Herpes Simplex Virus-1 than Standard Acyclovir (− 6.5 kcal/mol). Upon further investigation, the binding affinities of primary limonene were observed to be slightly poor. But including the various functional groups also increases the affinities and capacity to prevent viral infection of the capsid protein of Herpes Simplex Virus-1. Then, the molecular dynamic simulation confirmed that the mentioned ligands might be stable during the formation of drug-protein complexes. Finally, the analysis of ADMET was essential in establishing them as safe and human-useable prospective chemicals. According to the present findings, limonene derivatives might be a promising candidate against the capsid protein of Herpes Simplex Virus-1 which ultimately inhibits Herpes Simplex Virus-induced encephalitis that causes interventions in brain inflammation. Our findings suggested further experimental screening to determine their practical value and utility. [ABSTRACT FROM AUTHOR]

Human T-cell leukemia virus 1 (HTLV-1) associated lymphoma is a devastating malignancy triggered by HTLV-1 infections. We employeda comprehensive drug design and computational strategy in this work to explore the inhibitory activitiesof Astilbin derivatives against HTLV-1-associated lymphoma. We evaluated the stability, binding affinities, and various computational analysis of Astilbin derivatives against target proteins, such as HTLV-1 main protease and HTLV-1 capsid protein. The root mean square deviation (RMSD), root mean square fluctuation, radius of gyration, hydrogen bond analysis, principal component analysis (PCA) and dynamic cross-correlation matrix (DCCM) were applied to characterize these protein-ligand interactions further. Ligand-03 and ligand-04 exhibited notable binding affinity to HTLV-1 capsid protein, while ligand-05 displayed high binding affinity to HTLV-1 protease. MD simulation analysis revealed that ligand-03, bound to HTLV-1 capsid protein, demonstrated enhanced stability with lower RMSD values and fewer conformational changes, suggesting a promising binding orientation. Ligand-04, despite stable binding, exhibited increased structural deviations, making it less suitable. Ligand-05 demonstrated stable binding to HTLV-1 protease throughout the simulation period at 100 nanoseconds. Hydrogen bond analysis indicated that ligand-05 formed persistent hydrogen bonds with significantresidues, contributing to its stability. PCA highlighted ligand-03's more remarkable conformational changes, while DCCM showed ligand-05's distinct dynamics, indicating its different behavior in the complex. Furthermore, binding free energy calculations supported the favorable interactions of ligand-03 and ligand-04 with HTLV-1 capsid protein, while ligand-05 showed weaker interactions with HTLV-1 protease. Molecular electrostatic potential and frontier molecular orbital analyses provided insights into these compounds' charge distribution and stability. In conclusion, this research found Astilbin derivatives as potential inhibitors of HTLV-1-associated lymphoma. Future attempts at drug development will benefit from the steady interaction landscape provided by Ligand-03, Ligand-04 and Ligand-05, which showed the most attractive binding profile with the target protein. These results open up new opportunities for innovative drug development, and more experimental testing should be done between Astilbin derivatives and HTLV-1-associated lymphoma.Communicated by Ramaswamy H. Sarma.