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1.
J Agric Food Chem ; 72(13): 6998-7009, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38507729

ABSTRACT

Chemical exploration for two isolates of the recently described ascomycete species Polyphilus sieberi, derived from the eggs of the plant parasitic nematode Heterodera filipjevi, afforded the identification of many compounds that belong to various metabolite families: two previously undescribed chlorinated cyclotetrapeptides, omnipolyphilins A (1) and B (2), one new pyranonaphthoquinone, ventiloquinone P (3), a 6,6'-binaphto-α-pyranone dimer, talaroderxine D (4) in addition to nine known metabolites (5-13) were isolated from this biocontrol candidate. All isolated compounds were characterized by comprehensive 1D, 2D NMR, and HR-ESI-MS analyses. The absolute configurations of the cyclotetrapeptides were determined by a combination of advanced Marfey's method, ROE correlation aided by conformational analysis, and TDDFT-ECD calculations, while ECD calculations, Mosher's method, and experimental ECD spectra were used for ventiloquinone P (3) and talaroderxine D (4). Among the isolated compounds, talaroderxine D (4) showed potent antimicrobial activities against Bacillus subtilis and Staphylococcus aureus with MIC values of 2.1 and 8.3 µg mL-1, respectively. Additionally, promising inhibitory effects on talaroderxine D (4) against the formation of S. aureus biofilms were observed up to a concentration of 0.25 µg mL-1. Moreover, ophiocordylongiiside A (10) showed activity against the free-living nematode Caenorhabditis elegans.


Subject(s)
Ascomycota , Tylenchoidea , Humans , Animals , Staphylococcus aureus , Bacillus subtilis , Molecular Structure
2.
Chem Biodivers ; 21(4): e202400385, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38421379

ABSTRACT

Chemical prospection of an extract derived from a saprotrophic fungus Lachnum sp. IW157 resulted in the isolation and characterization of six unprecedentedly reported ambuic acid analogues named lachnuoic acids A-F (1-6). Chemical structures of 1-6 were determined based on comprehensive 1D and 2D NMR spectroscopic analyses together with HR-ESI-MS spectrometry. The relative configurations of 1-3 were defined by ROESY spectroscopic analyses while their absolute configurations were unambiguously determined by Mosher's esters method. All isolated compounds were subjected to cytotoxic, antimicrobial, antibiofilm and nematicidal activity assays where only lachnuoic acid A (1) revealed potent antimicrobial activity against Staphylococcus aureus and Bacillus subtilis at MIC values of 16.6 and 8.3 µg/mL, respectively.


Subject(s)
Anti-Infective Agents , Ascomycota , Molecular Structure , Ascomycota/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Cyclohexanones
3.
ACS Omega ; 8(44): 41689-41695, 2023 Nov 07.
Article in English | MEDLINE | ID: mdl-37970032

ABSTRACT

Chemical investigation for the mycelial extract of a saprotrophic fungus Lachnum sp. IW157 growing on the common reed grass Phragmites communis afforded the identification of two polyketide metabolites diaporphasines E (1) and F (2). Chemical structures of isolated compounds were unambiguously elucidated based on extensive 1D and 2D NMR spectral analyses in addition to their high-resolution mass spectrometry. The isolated compounds were assessed for their cytotoxicity and antimicrobial and biofilm inhibitory activities. While compound 1 revealed potent cytotoxicity against the tested cell lines L929 and KB3.1 with IC50 values of 0.9 and 3.7 µM, respectively, compound 2 exhibited moderate effects on the formation of S. aureus biofilms at 31.25 µg/mL.

4.
Cureus ; 15(4): e37459, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37187622

ABSTRACT

Abdominal tuberculosis (TB) is a common form of extrapulmonary TB (EXPTB). It is being reported increasingly, especially in high-burden regions of the world. We present a case of a 37-year-old male who presented to the emergency department with clinical features suggestive of bowel obstruction. On clinical examination, the patient exhibited generalized tenderness in the abdomen. A subsequent CT scan revealed features consistent with small bowel obstruction. The patient underwent a diagnostic laparoscopy, which was converted to an exploratory laparotomy due to intraoperative findings of adhesions. Notably, there were extensive peritoneal deposits and adhesions between bowel loops. Peritoneal biopsies were obtained and subjected to the acid-fast bacillus (AFB) smear and culture, which demonstrated the growth of the Mycobacterium tuberculosis complex. As a result, the patient was initiated on antituberculous therapy.

5.
Metallomics ; 9(7): 902-909, 2017 07 19.
Article in English | MEDLINE | ID: mdl-28561856

ABSTRACT

Trivalent lanthanum (La3+) has the potential to treat bone resorption disorders (such as osteoporosis) by eliciting a bone-building response in the cells which control skeletal remodelling. Because La3+ suffers from extremely poor intestinal absorption, specifically designed chelators are required in order that a biologically active form of lanthanum can be administered orally. Two such chelators, 1,2-dimethyl-3-hydroxy-4-pyridinone (Hdpp) and bis-{[bis(carboxymethyl)amino]methy}phosphinic acid (H5XT), have previously been the subjects of extensive physical, in vitro, and in vivo testing as the tris- and mono-lanthanum(iii) complexes La(dpp)3 and La(XT), respectively. In this manuscript, we expand upon those studies to include 4-week intravenous (IV) and oral La3+ biodistribution profiles, which show that the metal ion initially accumulates in the liver followed by preferential redistribution and retention by bone. Of the two compounds, La(XT) demonstrates the more favourable in vivo characteristics, therefore dose-dependent oral biodistribution studies were carried out with this complex. These show drug saturation above a dose of 100 mg kg-1 day-1, so liver histology was performed in order to assess any potential toxicity. Finally, we improve upon the physical characterization of La(dpp)3 to include a single crystal X-ray structure, which exhibits an 8-coorindate La3+ centre with two bound water molecules, and a disordered exoclathrate-type hydrogen bonded network.


Subject(s)
Bone Resorption/drug therapy , Lanthanum/administration & dosage , Lanthanum/therapeutic use , Administration, Intravenous , Administration, Oral , Animals , Bone Resorption/blood , Bone Resorption/pathology , Creatinine/blood , Crystallography, X-Ray , Dose-Response Relationship, Drug , Lanthanum/chemistry , Liver/enzymology , Molecular Conformation , Rats , Tissue Distribution
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