Artemisia herba-alba sesquiterpenes: in silico inhibition in the ATP-binding pocket.

To identify antimicrobial leads for medical applications, metabolites from the aerial part of Artemisia herba-alba were extracted and chromatographically purified. Two new sesquiterpenes, 1ß,8α-dihydroxyeudesm-4-en-6ß,7α,11ßH-12,6-olide (1) and 1ß,6α,8α-trihydroxy, 11α-methyl-eudesma-4(15)-en-13-propanoate (2) along with a known eudesmanolide 11-epi-artapshin (3) were identified. Structures were determined by spectroscopic methods including 1D- and 2D-NMR as well as mass spectroscopy. Compound 3 inhibited Gram-positive bacteria Bacillus subtilis, Lactobacillus cereus and Staphylococcus aureus and exhibited antifungal activity against the pathogenic fungus F. solani. The mode-of-action of these antimicrobial sesquiterpenes as bacterial type II DNA topoisomerase and/or DNA gyrase B inhibitors were examined via in silico studies. Such molecular-docking studies were also employed to examine antifungal activity against an N-myristoyl transferase (NMT) target. Compound 3 had the greatest gyrase B binding affinity in the ATP-binding pocket and was found to possess an inhibitory action against non-invasive micro-test technology (NMT).

Sarcoconvolutums F and G: Polyoxygenated Cembrane-Type Diterpenoids from Sarcophyton convolutum, a Red Sea Soft Coral.

Natural products and chemical analogues are widely used in drug discovery, notably in cancer and infectious disease pharmacotherapy. Sarcophyton convolutum (Alcyoniidae) a Red Sea-derived soft coral has been shown to be a rich source of macrocyclic diterpenes and cyclized derivatives. Two previously undescribed polyoxygenated cembrane-type diterpenoids, sarcoconvolutums F (1) and G (2), as well as four identified analogues (3-6) together with a furan derivate (7) were isolated from a solvent extract. Compounds were identified by spectroscopic techniques, including NMR, HREIMS, and CD, together with close spectral comparisons of previously published data. Sarcoconvolutum F (1) contains a rare 1-peroxid-15-hydroxy-10-ene functionality. Isolated metabolites (1-7) were screened against lung adenocarcinoma (A549), cervical cancer (HeLa) and oral cavity carcinoma (HSC-2) lines. Compound 4 exhibited an IC50 56 µM and 55 µM against A549 and HSC-2 cells, respectively.

Plant cell cultures: An enzymatic tool for polyphenolic and flavonoid transformations.

BACKGROUND: In the pharmaceutical sector, tissue culture techniques for large-scale production of natural chemicals can be a less expensive alternative to large-scale synthesis. Although recent biotransformation research have used plant cell cultures to target a wide range of bioactive compounds, more compiled information and synopses are needed to better understand metabolic pathways and improve biotransformation efficiencies. PURPOSE: This report reviews the biochemical transformation of phenolic natural products by plant cell cultures in order to identify potential novel biotechnological approaches for ensuring more homogeneous and stable phenolic production year-round under controlled environmental conditions. METHODS: Articles on the use of plant cell culture for polyphenolic and flavonoid transformations (1988 - 2021) were retrieved from SciFinder, PubMed, Scopus, and Web of Science through electronic and manual search in English. Following that, the authors chose the required papers based on the criteria they defined. The following keywords were used for the online search: biotransformation, Plant cell cultures, flavonoids, phenolics, and pharmaceutical products. RESULTS: The initial search found a total of 96 articles. However, only 70 of them were selected as they met the inclusion criteria defined by the authors. The analysis of these studies revealed that plant tissue culture is applicable for the large-scale production of plant secondary metabolites including the phenolics, which have high therapeutic value. CONCLUSION: Plant tissue cultures could be employed as an efficient technique for producing secondary metabolites including phenolics. Phenolics possess a wide range of therapeutic benefits, as anti-oxidant, anti-cancer, and anti-inflammatory properties. Callus culture, suspension cultures, transformation, and other procedures have been used to improve the synthesis of phenolics. Their production on a large scale is now achievable. More breakthroughs will lead to newer insights and, without a doubt, to a new era of phenolics-based pharmacological agents for the treatment of a variety of infectious and degenerative disorders.

Gastroprotection against Rat Ulcers by Nephthea Sterol Derivative.

Different species belonging to the genus Nephthea (Acyonaceae) are a rich resource for bioactive secondary metabolites. The literature reveals that the gastroprotective effects of marine secondary metabolites have not been comprehensively studied in vivo. Hence, the present investigation aimed to examine and determine the anti-ulcer activity of 4α,24-dimethyl-5α-cholest-8ß,18-dihydroxy,22E-en-3ß-ol (ST-1) isolated from samples of a Nephthea species. This in vivo study was supported by in silico molecular docking and protein-protein interaction techniques. Oral administration of ST-1 reduced rat stomach ulcers with a concurrent increase in gastric mucosa. Molecular docking calculations against the H+/K+-ATPase transporter showed a higher binding affinity of ST-1, with a docking score value of -9.9 kcal/mol and a pKi value of 59.7 nM, compared to ranitidine (a commercial proton pump inhibitor, which gave values of -6.2 kcal/mol and 27.9 µM, respectively). The combined PEA-reactome analysis results revealed promising evidence of ST-1 potency as an anti-ulcer compound through significant modulation of the gene set controlling the PI3K signaling pathway, which subsequently plays a crucial role in signaling regarding epithelialization and tissue regeneration, tissue repairing and tissue remodeling. These results indicate a probable protective role for ST-1 against ethanol-induced gastric ulcers.