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Antimicrobial resveratrol tetramers from the stem bark of Vatica oblongifoliassp. oblongifolia

Zgoda-Pols JR, Freyer AJ, Killmer LB, Porter JR

J Nat Prod, 2002 Nov;65(11):1554-9.
PMID: 12444676

Two new resveratrol tetramers, hopeaphenol A (1) and isohopeaphenol A (2), along with the known vaticaphenol A (3), were isolated from the stem bark of Vatica oblongifolia ssp. oblongifolia through bioassay-guided fractionation. The structures and their relative stereochemistry were determined by spectroscopic techniques. Compounds 1 and 3 demonstrated moderate activity against methicillin-resistant Staphylococcus aureus and Mycobacterium smegmatis.

Matched MeSH terms: Mycobacterium smegmatis/drug effects
Fulltext Combating Intracellular Pathogens with Nanohybrid-Facilitated Antibiotic Delivery

Bose RJC, Tharmalingam N, Choi Y, Madheswaran T, Paulmurugan R, McCarthy JR, et al.

Int J Nanomedicine, 2020;15:8437-8449.
PMID: 33162754 DOI: 10.2147/IJN.S271850

BACKGROUND: Lipid polymer hybrid nanoparticles (LPHNPs) have been widely investigated in drug and gene delivery as well as in medical imaging. A knowledge of lipid-based surface engineering and its effects on how the physicochemical properties of LPHNPs affect the cell-nanoparticle interactions, and consequently how it influences the cytological response, is in high demand.
METHODS: Herein, we have engineered antibiotic-loaded (doxycycline or vancomycin) LPHNPs with cationic and zwitterionic lipids and examined the effects on their physicochemical characteristics (size and charge), antibiotic entrapment efficiency, and the in vitro intracellular bacterial killing efficiency against Mycobacterium smegmatis or Staphylococcus aureus infected macrophages.
RESULTS: The incorporation of cationic or zwitterionic lipids in the LPHNP formulation resulted in a size reduction in LPHNPs formulations and shifted the surface charge of bare NPs towards positive or neutral values. Also observed were influences on the drug incorporation efficiency and modulation of the drug release from the biodegradable polymeric core. The therapeutic efficacy of LPHNPs loaded with vancomycin was improved as its minimum inhibitory concentration (MIC) (2 µg/mL) versus free vancomycin (4 µg/mL). Importantly, our results show a direct relationship between the cationic surface nature of LPHNPs and its intracellular bacterial killing efficiency as the cationic doxycycline or vancomycin loaded LPHNPs reduced 4 or 3 log CFU respectively versus the untreated controls.
CONCLUSION: In our study, modulation of surface charge in the nanomaterial formulation increased macrophage uptake and intracellular bacterial killing efficiency of LPHNPs loaded with antibiotics, suggesting alternate way for optimizing their use in biomedical applications.

Matched MeSH terms: Mycobacterium smegmatis/drug effects
5'-Methoxyarmillane, a Bioactive Sesquiterpenoid Aryl Ester from the Fungus Armillaria ostoyae

Orban AM, Eichberg J, Marner M, Breuer S, Patras MA, Mettal U, et al.

Chembiochem, 2024 Nov 04;25(21):e202400168.
PMID: 38738599 DOI: 10.1002/cbic.202400168

Higher fungi of the genus Armillaria belonging to the phylum Basidiomycota produce bioactive sesquiterpenoid aryl esters called melleolides. A bioactivity-guided discovery process led to the identification of the new melleolide 5'-methoxyarmillane (1) in organic extracts from the mycelium of Armillaria ostoyae. Remarkably, supplementation of rapeseed oil to the culture medium potato dextrose broth increased the production of 1 by a factor of six during the course of the 35 days fermentation. Compound 1 was isolated and its structure elucidated by UHPLC-QTOF-HR-MS/MS and NMR spectroscopy. It showed toxicity against Madin-Darby canine kidney II (MDCK II, IC50 19.2 μg/mL, 44.1 μM) and human lung cancer Calu-3 cells (IC50 15.2 μg/mL, 34.9 μM) as well as moderate bioactivity against Mycobacterium tuberculosis (MIC 8 mg/mL, 18.4 μM) and Mycobacterium smegmatis (MIC 16 mg/mL, 36.8 μM), but not against Staphylococcus aureus, Escherichia coli, Candida albicans, and Septoria tritici. No inhibitory effects of 1 against the influenza viruses H3N2, H1N1pdm, B/Malaysia, and B/Massachusetts were observed.

Matched MeSH terms: Mycobacterium smegmatis/drug effects
Fulltext 4'-O-substitutions determine selectivity of aminoglycoside antibiotics

Perez-Fernandez D, Shcherbakov D, Matt T, Leong NC, Kudyba I, Duscha S, et al.

Nat Commun, 2014;5:3112.
PMID: 24473108 DOI: 10.1038/ncomms4112

Clinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4',6'-O-acetal and 4'-O-ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact poorly with the drug-binding pocket of eukaryotic mitochondrial or cytosolic ribosomes. Yet, these compounds largely retain their inhibitory activity for bacterial ribosomes and show antibacterial activity. Our data indicate that 4'-O-substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets.

Matched MeSH terms: Mycobacterium smegmatis/drug effects