Chemistry & Biodiversity最新文献

Breast cancer (BRCA) incidence is increasing, posing a significant public health challenge and necessitating effective treatment solutions. Nauclea latifolia (N. latifolia) has shown anticancer activity against multidrug-resistant BRCA cells, though its mechanism of action remains unclear. We used online databases Swiss target prediction and GeneCards to identify therapeutic targets for BRCA and active compounds in N. latifolia. Protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. Molecular docking, gene expression and survival analyses of core targets were conducted using Autodock 4.0 and GEPIA2 database. We identified 141 intersecting targets for BRCA and N. latifolia compounds, with key targets including ALB, AKT1, ESR1, STAT3, EGFR, SRC, PTGS2, GSK3B, MMP9, and PPAR1. These targets are involved in cell proliferation and death through pathways such as the PI3K-Akt signaling system, metabolic pathways, cancer pathways, and proteoglycans in cancer. Gene expression and survival analysis indicated these targets as potential markers for BRCA treatment prognosis. This study provides insights into the mechanism of action of N. latifolia against BRCA cells and give a basis to clinicians for future drug development.

Phytochemical investigation into the fruits of Schisandra chinensis led to the isolation of seven new minor lignans, schisanchignans A-G (1-7), including one benzofuran type (1), three aryltetralin type (2-4) and three tetrahydrofuran type (5-7). Their structures were established by comprehensive spectroscopic analyses, and the absolute configurations were determined by electronic circular dichroism technique including quantum chemical calculation method. Of note, this is the first report of nor-benzofuran and aryltetralin types of lignans from S. chinensis. Compounds 1, 3 and 4 exhibited mild inhibitory activity against the lipopolysaccharide-induced production of nitric oxide in murine RAW264.7 cells.

Plants are the major source of natural flavour ingredients reported for their wide applications in food and pharmaceuticals, oral care and wellness products, etc. We have investigated the water-soluble fractions (WSF) of basil tetraploid (O. basilicum L.) for their toxicity and biological potential against Salmonella Typhimurium, a pathogen causing around one million cases of illnesses in the United States every year. The WSF obtained using a Clevenger-type apparatus was further divided into two equal parts, one each for in-vivo toxicity evaluation and quality assessments, respectively. The proportions of major phenylpropanoid identified as meta-eugenol in the WSF were found in the range of 42.8-57.9%, which was substantially in higher proportion as compared to essential oil (20.9-23.0%). Based on sub-acute oral toxicity data, WSF has not shown any adverse effect with levels as high as 500 µL/25g body weight in Swiss albino mice. Besides, the WSF also exhibited a maximum reduction in bacterial load in mice infected with Salmonella Typhimurium in a dose-dependent manner. We have shown the biological potential of basil water-soluble fraction as an effective bacterial load-suppressing agent for the prevention of Salmonella infections in animal model.

Rubia tibetica Hook. f is a traditional Tibetan medicinal plant, with its roots serving as the primary medicinal part. Two new compounds, Rubiaxylm C and E (1 and 3), and one new natural compound, Rubiaxylm D (2) were isolated from R. tibetica, along with five known compounds (4-8). The structures of the previously undescribed compounds were elucidated by HR-ESIMS, 1D/2D NMR spectroscopic data and electronic circular dichroism calculations. Compound 1 is a rare anthrone substituted with a carbonyl group at position 1. Furthermore, all isolated compounds were tested for their cytotoxicity against HepG2 cell lines.

Diabetes is a major global health issue and as current treatments fail, the search for new antidiabetic drugs is crucial. This investigation, focusing on identifying potential antidiabetic compounds from the endangered plant species Vepris glandulosa, led to the isolation of two known alkaloids, choisyine acetate (1) and choisyine (2). The study established the in vitro inhibitory activities and in silico molecular interaction of the two alkaloids with α-amylase based on IC50 values, Linewaever-Burk/Dixon plot kinetic analyses and Molecular docking, respectively. The α-amylase inhibition assay revealed noncompetitive inhibition for both compounds with IC50 and Ki values of 4.74±0.17 and 4.75 mM for compound 1, and 11.29±0.44 and 12.37 mM for compound 2, respectively. In comparison, the standard drug acarbose displayed a competitive mode of inhibition, with IC50 and Ki values of 11.99±0.02 and 12.68 mM, respectively. The binding affinities with α-amylase were -6.42 and -6.07 kcal/mol for compounds 1 and 2, respectively relative to acarbose -8.03 Kcal/mol. Moreover, the predicted physicochemical and ADMET properties of these two compounds justified their potential as lead compounds for drug discovery. These compounds demonstrated remarkable inhibition potential comparable to the standard drug, highlighting their potential as viable alternatives in the management of diabetes.

Three new putative sequences of 14-residue peptaibols, named amazonins I-III were characterized from the endophytic fungus Trichoderma amazonicum via genome mining, high-performance liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS), and molecular networking. Bioinformatic analysis of the T. amazonicum genome assembly revealed 63 clusters of biosynthetic genes (BGCs) related to secondary metabolites, including a nonribosomal peptide synthetase accountable for the biosynthesis of the discovered peptide sequences. Analysis of the adenylation domains, along with manual interpretation of MS/MS spectra, allowed extensive annotation of the new peptaibol sequences. The combination of bioinformatic tools and LC-MS/MS provides a better opportunity to characterize and identify new peptaibol sequences. Thus, the importance of studies on the production and characterization of peptaibols produced by Trichoderma species from the Amazon region is highlighted.

Herein, the synthesis, anti-cancer evaluation, and in silico studies of a series of 1,2,4-oxadiazole compounds (8-15) are disclosed. The synthesized molecules were tested in vitro for anti-cancer activity against MCF-7, MDA-MB-231, HeLa, Ishikawa cell lines and human embryonic kidney (HEK-293) cell lines. Among the synthesized compounds, 9 and 15 exhibited significant cytotoxicity, with IC50 values of 7.82 μM and 6.02 μM, respectively, against MCF-7 cell line, better than that of anti-breast cancer drug, tamoxifen (IC50 = 11.92 μM), used as control. Significantly, both 9 and 15 exhibited very low toxicity (IC50 > 20 µM) against normal HEK-293 cells. This suggests them as potentially effective anti-cancer lead molecules. The in vitro anti-cancer data was supported by in silico studies which also identified compounds 9 and 15 as potent inhibitors of the 17β-hydroxysteroid dehydrogenase1 (17β-HSD1) proteins, demonstrating strong interactions and stability The atom-based QSAR model exhibited high accuracy, significant regression, and predictive reliability, aiding in understanding and optimizing biological activity. The drug-likeness study of compounds 9 and 15 indicated favorable pharmacokinetics, with in silico toxicity predictions showing compound 15 to be non-toxic. These findings suggest compounds 9 and 15 as potential lead molecules against breast cancer.

This study investigates the wound-healing potential of Euphorbia guyoniana latex (EGL) in male Wistar rats, along with its biochemical composition and biological activities. Phytochemical analysis identified moderate levels of phenolics, flavonoids, and tannins, with HPLC revealing five phenolic compounds. EGL demonstrated strong antioxidant activity in DPPH assays, surpassing ascorbic acid in protecting red blood cells. Its performance in the ß-carotene-linoleic acid assay was robust, though its FRAP assay results were weaker. EGL also exhibited significant anti-inflammatory activity, comparable to Acetylsalicylic acid, and showed antibacterial effects against Listeria innocua. In Vivo, EGL-infused ointments accelerated wound healing, reducing epithelialization periods to 12-16 days, with a higher wound contraction rate compared to controls. The study concludes that EGL, rich in bioactive compounds, holds potential as a promising natural agent for wound healing, owing to its potent antioxidant, anti-inflammatory, and antibacterial properties.

O-alkylation of the hydroxy compounds, including acetaminophen, starting compounds for the synthesis of the drug, and natural compounds with the bromides of dihydroartemisinin (DHA) and zerumbone, produced twenty novel ether conjugates 15a-j and 16a-j, respectively. Their structures were elucidated by 1D-, 2D-NMR, and HRMS data. Their in vitro cytotoxic activity was screened using three cancer cell lines: HepG2, HeLa, and PC-12. The results showed that eight out of ten conjugates in series 15a-j containing DHA skeleton exhibited activity against the tested cell lines, with IC50 values ranging from 4.26-47.37 µM. Notably, all conjugates in series 16a-j containing zerumbone scaffolds inhibited the growth of HepG2, HeLa, and PC12 with IC50 in the range of 4.46-35.07 µM. Using network pharmacology and molecular docking to target anti-liver cancer in the above 20 synthetic compounds, 271 intersection targets were discovered, including 5 targets with high degree values (EGFR, ESR1, AKT1, MDM2, and NFKB1). Artemisinin derivative 15i gave the highest binding energy for targets AKT1, EGFR, and NFKB1, while zerumbone-murrayafoline A ether 16g in the remaining series also gave the highest energy for proteins EGFR, AKT1, and NFKB1.

The study aimed to assess the effectiveness of these formulations against  S. maltophilia in terms of their antimicrobial and anti-biofilm properties. The physicochemical characteristics of HM-PULL-Tetracycline were analyzed using a field scanning electron microscope, X-ray dispersion, Zeta potential, and dynamic light scattering analysis. The antibacterial and anti-biofilm activity was assessed using minimal biofilm inhibitory concentration and broth micro-dilution. In addition, the biocompatibility of HM-PULL-Tetracycline was assessed by investigating its cytotoxicity on the human diploid fibroblasts (HDF) normal cell line using the MTT test. The HM-PULL-Tetracycline formulation successfully prevented biofilm formation, measuring 179.7± 2.66 nm in size and with an encapsulation efficiency of 84.86± 3.14%. It exhibited a biofilm growth inhibition rating of 69% and significantly down-regulated the expression of the smf-1, rpfF, rmlA, and spgM biofilm genes in S. maltophilia strains (p<0.05). Furthermore, the HM-PULL-Tetracycline formulation exhibited a 4 to 6-fold increase in antibacterial efficacy compared to unbound tetracycline. The HM-PULL-Tetracycline formulation demonstrated cell viability of over 90% at all doses tested against HDF normal cells. The findings of the current investigation demonstrate that HM-PULL-Tetracycline enhances the bactericidal and anti-biofilm properties without causing harm to healthy human cells. This suggests that Could be a promising approach for medication administration.