Search

Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic disease and dengue shock syndrome (DSS), transmitted predominantly in tropical and subtropical regions by Aedes aegypti. It infects millions of people and causes thousands of deaths each year, but there is no antiviral drug against DENV. Usnic acid lately piqued the interest of researchers for extraordinary biological characteristics, including antiviral activity. Based on high larvicidal activities against Aedes aegypti, this study aims to search usnic acid derivatives as novel anti-DENV agents through a combination of ligand-based and pharmacophore-based virtual screening. One hundred and sixteen (116) usnic acid derivatives were obtained from a database of 428 in-house usnic acid derivatives through pharmacophore filtering steps. Subsequent docking simulation on DENV-3 NS-5 RdRp afforded 41 compounds with a strong binding affinity towards the enzyme. The pharmacokinetics and drug likeness prediction resulted in seven hit compounds, which eventually undergo cytochrome P450 enzyme screening to obtain the lead compound, labelled as 362. In addition, molecular dynamic (MD) simulation of lead compound 362 was performed to verify the stability of the docked complex and the binding posture acquired in docking experiments. Overall, the lead compounds have shown a high fit value of pharmacophore, strong binding affinity towards RdRp enzyme, good pharmacokinetics, and drug likeness properties. The discovery of a new usnic acid derivative as a novel anti-DENV agent targeting RdRp could lead to further drug development and optimization to treat dengue.

The current data report describes the predictive identification of phytochemical constituents in the bioactive extract of Ipomoea mauritiana (IM) whole plant. For several formulations this plant was commonly used as ‘Vidari’ for Ayurvedic medicine. Traditionally, IM tubers are used to alleviate spinal cord pain, improve breast milk, as a tonic, increase sperm count and treating jaundice. The methanol extract can potentially scavenge free radicals and possess antibacterial activity that could be correlated with its chemical composition. So it is crucial to identify the major compounds of IM. An ultra-performance liquid chromatography coupled electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF/MS) method was adopted to detect the flavonoids, saponins, alkaloids, terpenoids in IM methanol extract. Data presented here is related to a published work Antioxidant and antibacterial activity of Ipomoea mauritiana Jacq.: A traditionally used medicinal plant in Bangladesh (Alam et al., 2020). Secondary metabolites were analyzed by the comparison of the mass fragmentation arrangements with Waters UNIFI library that enables for positive identification of the compounds based on the spectral match.

This research investigated a UPLC-QTOF/ESI-MS-based phytochemical profiling of Combretum indicum leaf extract (CILEx), and explored its in vitro antioxidant and in vivo antidiabetic effects in a Long–Evans rat model. After a one-week intervention, the animals’ blood glucose, lipid profile, and pancreatic architectures were evaluated. UPLC-QTOF/ESI-MS fragmentation of CILEx and its eight docking-guided compounds were further dissected to evaluate their roles using bioinformatics-based network pharmacological tools. Results showed a very promising antioxidative effect of CILEx. Both doses of CILEx were found to significantly (p &lt, 0.05) reduce blood glucose, low-density lipoprotein (LDL), and total cholesterol (TC), and increase high-density lipoprotein (HDL). Pancreatic tissue architectures were much improved compared to the diabetic control group. A computational approach revealed that schizonepetoside E, melianol, leucodelphinidin, and arbutin were highly suitable for further therapeutic assessment. Arbutin, in a Gene Ontology and PPI network study, evolved as the most prospective constituent for 203 target proteins of 48 KEGG pathways regulating immune modulation and insulin secretion to control diabetes. The fragmentation mechanisms of the compounds are consistent with the obtained effects for CILEx. Results show that the natural compounds from CILEx could exert potential antidiabetic effects through in vivo and computational study.

Hormone replacement therapy has been a conventional treatment for postmenopausal symptoms in women. However, it has potential risks of breast and endometrial cancers. The aim of this study was to evaluate the oestrogenicity of a plant-based compound, mimosine in MCF-7 cells and by in silico model. Cell viability and proliferation, ERα-SRC1 coactivator activity and expression of specific ERα-dependent marker TFF1 and PGR genes were evaluated. Binding modes of 17β-oestradiol and mimosine at the ERα ligand binding domain were compared using docking and molecular dynamics simulation experiments followed by binding interaction free energy calculation with molecular mechanics/Poisson Boltzmann surface area. Mimosine showed increased cellular viability (64450 cells/mL) at 0.1 μM with significant cell proliferation (120.5%) compared to 17β-oestradiol (135.2%). ER antagonist tamoxifen significantly reduced proliferative activity mediated by mimosine (49.9%). Mimosine at 1 μM showed the highest ERα binding activity through increased SRC1 recruitment at 186.9%. It expressed TFF1 (11.1 fold at 0.1 μM) and PGR (13.9 fold at 0.01 μM) genes. ERα-mimosine binding energy was -49.9 kJ/mol and it interacted with Thr347, Gly521 and His524 of ERα-LBD. The results suggested that mimosine has oestrogenic activity. This article is protected by copyright. All rights reserved.