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1.
Biosci Biotechnol Biochem ; 86(1): 31-36, 2021 Dec 22.
Article in English | MEDLINE | ID: mdl-34734225

ABSTRACT

2-Methylthio-N7-methyl-cis-zeatin (1) was isolated from the culture broth of Streptomyces sp. 80H647 along with 2 known purine derivatives, 5'-methylthioinosine (2) and AT-265 (dealanylascamycin, 3). The structure elucidation of compound 1 was accomplished by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) analyses. It inhibited the growth of Plasmodium falciparum 3D7 with a GI50 of 2.4 µm and had no effect on the growth of Arabidopsis at 2 µm. This is the first report of an N7-methylated zeatin-type natural product from Streptomyces and as an antimalarial compound.


Subject(s)
Antimalarials
2.
J Antibiot (Tokyo) ; 74(7): 477-479, 2021 07.
Article in English | MEDLINE | ID: mdl-33879862

ABSTRACT

N-acetyl-α-hydroxy-ß-oxotryptamine (1) along with N-acetyl-ß-oxotryptamine (2) and pimprinine (3) were isolated from the culture broth of Streptomyces sp. 80H647. Compound 1 was found to be a racemate via X-ray diffraction analysis and the enantiomers were successfully purified by chiral-phase HPLC. The absolute configuration was assigned by comparison of the calculated and experimental ECD spectra. The α-hydroxy moiety of 1 was vital for cytotoxicity against different cancer cell lines.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Biological Products/chemistry , Streptomyces/chemistry , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Biological Products/pharmacology , Cell Line, Tumor , Crystallography, X-Ray , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , Stereoisomerism , Structure-Activity Relationship , Tryptamines/chemistry
3.
J Antibiot (Tokyo) ; 72(12): 991-995, 2019 12.
Article in English | MEDLINE | ID: mdl-31395970

ABSTRACT

A new siderophore glucuronide, nocardamin glucuronide (1), was isolated together with nocardamin (2) by applying the one strain-many compounds (OSMAC) approach to the ascamycin-producing strain, Streptomyces sp. 80H647, and performing multivariate analysis using mass spectral data. Structure elucidation was accomplished by a combination of NMR and MS analyses. The absolute configuration of the glucuronic acid moiety was found to be ß-D-GlcA by hydrolysis using ß-glucuronidase, subsequent derivatization of the hydrolysate, and comparison with standards. The siderophore activity of 1 was evaluated through the chrome azurol S assay and was comparable to that of 2 and deferoxamine (IC50 13.4, 9.5, and 6.3 µM, respectively). Nocardamin glucuronide (1) is the first example of a siderophore glucuronide.


Subject(s)
Siderophores/chemistry , Siderophores/pharmacology , Streptomyces/metabolism , Adenosine/analogs & derivatives , Adenosine/metabolism , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antimalarials/chemistry , Antimalarials/pharmacology , Cell Line, Tumor , Deferoxamine/pharmacology , Humans , Hydroxybenzoates/chemistry , Iron/metabolism , Magnetic Resonance Spectroscopy , Mass Spectrometry/statistics & numerical data , Molecular Structure , Peptides, Cyclic/isolation & purification , Principal Component Analysis , Siderophores/isolation & purification , Siderophores/toxicity , Toxicity Tests
4.
BMC Med Educ ; 18(1): 152, 2018 Jun 27.
Article in English | MEDLINE | ID: mdl-29945579

ABSTRACT

BACKGROUND: Mobile learning (mLearning) devices (such as tablets and smartphones) are increasingly part of the clinical environment but there is a limited and somewhat conflicting literature regarding the impact of such devices in the clinical learning environment. This study aims to: assess the impact of mLearning devices in the clinical learning environment on medical students' studying habits, attitudes towards mobile device supported learning; and the perceived reaction of clinicians and patients to the use of these devices as part of learning in the clinical setting. METHODS: Over three consecutive academic years, 18 cohorts of medical students (total n = 275) on a six-week rotation at a large teaching hospital in London were supplied with mLearning devices (iPad mini) to support their placement-based learning. Feedback on their experiences and perceptions was collected via pre- and post-use questionnaires. RESULTS: The results suggest mLearning devices have a positive effect on the students' perceived efficiency of working, while experience of usage not only confirmed pre-existing positive opinions about devices but also disputed some expected limitations associated with mLearning devices in the clinical workplace. Students were more likely to use devices in 'down-time' than as part of their clinical learning. As anticipated, both by users and from the literature, universal internet access was a major limitation to device use. The results were inconclusive about the student preference for device provision versus supporting a pre-owned device. CONCLUSION: M-learning devices can have a positive impact on the learning experiences medical students during their clinical attachments. The results supported the feasibility of providing mLearning devices to support learning in the clinical environment. However, universal internet is a fundamental limitation to optimal device utilisation.


Subject(s)
Attitude of Health Personnel , Cell Phone , Computers, Handheld , Education, Medical/methods , Learning , Students, Medical/psychology , Adult , Female , Hospitals, Teaching , Humans , London , Male , Perception , Surveys and Questionnaires , Young Adult
5.
J Nat Prod ; 80(10): 2708-2715, 2017 10 27.
Article in English | MEDLINE | ID: mdl-29019684

ABSTRACT

NMR- and MS-guided fractionation of an extract of an Okeania sp. marine cyanobacterium, collected from the Red Sea, led to the isolation of four new metabolites, including serinolamides C (1) and D (2) and lyngbyabellins O (3) and P (4), together with the three known substances lyngbyabellins F (5) and G (6) and dolastatin 16 (7). The planar structures of the new compounds were determined using NMR and MS analyses. The absolute configurations of 1 and 2 were determined by Marfey's analysis of their hydrolysates. The absolute configuration of 3 was ascertained by chiral-phase chromatography of degradation products, while that of 4 was determined by comparison to 3 and 5. The cytotoxic and antifouling activities of these compounds were evaluated using MCF7 breast cancer cells and Amphibalanus amphitrite larvae, respectively. Compounds 3, 4, and 7 exhibited strong antifouling activity, and 3 and 7 were not cytotoxic. A structure-activity relationship was observed for the cytotoxicity of the lyngbyabellins with the presence of a side chain (4 is more active than 3) leading to greater activity. For the antifouling activity, the acyclic form without a side chain (3) was the most active.


Subject(s)
Cyanobacteria/chemistry , Depsipeptides/isolation & purification , Lipids/isolation & purification , Animals , Biofouling/prevention & control , Breast Neoplasms , Depsipeptides/chemistry , Depsipeptides/pharmacology , Drug Screening Assays, Antitumor , Female , Humans , Indian Ocean , Lipids/chemistry , Lipids/pharmacology , Marine Biology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Structure-Activity Relationship , Thoracica/chemistry
6.
Org Lett ; 19(16): 4231-4234, 2017 08 18.
Article in English | MEDLINE | ID: mdl-28783344

ABSTRACT

Two new chlorinated fatty acid amides, columbamides D (1) and E (2), along with apratoxins A and C and wewakazole, were isolated from the organic extract of a Moorea bouillonii sample from Sabah, Malaysia. Structure elucidation was accomplished by a combination of MS and NMR analyses. The total synthesis of all four stereoisomers of 1 was completed, and the absolute configuration was determined by chiral-phase HPLC and Marfey's analysis.


Subject(s)
Amides/isolation & purification , Cyanobacteria/chemistry , Fatty Acids/isolation & purification , Amides/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Aquatic Organisms , Cell Line, Tumor , Drug Screening Assays, Antitumor/methods , Fatty Acids/chemistry , Halogenation , Humans , Malaysia , Molecular Conformation , Peptides, Cyclic/chemistry , Peptides, Cyclic/isolation & purification , Stereoisomerism
7.
J Nat Prod ; 79(4): 1213-8, 2016 Apr 22.
Article in English | MEDLINE | ID: mdl-26980238

ABSTRACT

A mass spectrometry (MS)-guided isolation has led to the purification of a new cyanobactin, wewakazole B (1), along with the known compound curacin D from a Red Sea Moorea producens. The planar structure of 1 was elucidated using a combination of NMR and MS techniques. After ozonolysis and acid hydrolysis, the absolute configurations of the amino acid components of 1 were determined by chiral-phase LC-MS and HPLC analyses. Notably, compound 1 exhibited cytotoxic activity toward human MCF7 breast cancer cells (IC50 = 0.58 µM) and human H460 lung cancer cells (IC50 = 1.0 µM) and was also found to be inactive in a siderophore assay.


Subject(s)
Antineoplastic Agents/pharmacology , Cyanobacteria/chemistry , Depsipeptides/isolation & purification , Depsipeptides/pharmacology , Peptides, Cyclic/pharmacology , Antineoplastic Agents/chemistry , Chromatography, High Pressure Liquid , Depsipeptides/chemistry , Drug Screening Assays, Antitumor , Humans , Indian Ocean , Lyngbya Toxins/chemistry , Marine Biology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Thiazoles/pharmacology
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