The yellow cedar tree, Chamaecyparis nootkatensis, collected in southeast Alaska was evaluated as a potential source of new anticancer agents. Two new diterpene anticancer constituents termed nootkastatins 1 (4) and 2 (5) were isolated along with three previously known diterpene cancer cell growth inhibitors where two were reported as synthetic modifications of totarol and not previously found in nature. All five diterpene structures were established by HRMS and 1D and 2D NMR spectroscopic analyses combined with three X-ray crystal structure determinations (2, 3, and 5). Against a panel of six human cancer cell lines, this series of diterpenes exhibited inhibition over the range GI(50) 0.75-2.0 microg/mL, and all inhibited the growth of Gram-positive bacteria and fungi.
Since 1991 information on yeast isolates from blood cultures has been recorded prospectively from all microbiological laboratories (5 university and 16 county or local hospital laboratories) in Norway (population, 4.3 million). From 1991 to 1996 a total of 571 episodes of fungemia in 552 patients occurred (1991, 109 episodes; 1992, 81 episodes; 1993, 93 episodes; 1994, 89 episodes; 1995, 98 episodes; and 1996, 101 episodes). The fungemia rates per 10,000 patient days were 0.29 in 1991 and 0.27 in 1996. The average rates for the years 1991 to 1996 were 0.37 for the university laboratories and 0.20 for the other laboratories. These rates are low compared to the rate (0. 76) in five Dutch university hospitals in 1995 and the rate (2.0) in Iowa in 1991. The four most frequently isolated species were Candida albicans (66%), Candida glabrata (12.5%), Candida parapsilosis (7.6%), and Candida tropicalis (6.4%). The incidences of both C. albicans (range, 63 to 73%) and C. glabrata (range, 8.4 to 15.7%) varied somewhat throughout this period, but no significant increase or decrease was noted. MICs of amphotericin B, flucytosine, and fluconazole were determined for 89% of the isolates. All were susceptible to amphotericin B, and only 29 (5.6%) strains had decreased susceptibility to flucytosine. All C. albicans isolates were susceptible to fluconazole. The percentage of yeast isolates with decreased susceptibility to fluconazole (MICs, >/=16 microgram/ml) did increase, from 9.6% in 1991 and 1992 to 12.2% in 1994, 16.1% in 1995, and 18.6% in 1996. This was largely due to increases in the percentages of resistant C. glabrata and Candida krusei strains in the last 2 years. Compared to the incidence in other countries, it is remarkable that Norway has such a low and constant incidence of fungemia. A possible reason for this difference might be a restricted antibiotic use policy in Norway.
BACKGROUND: The incidence of invasive fungal infections is increasing in parallel with an increase of patients with immunodeficiencies. Resistance to these drugs is becoming a problem in spite of increased and improved treatment options. MATERIAL AND METHODS: Literature retrieved from Medline and personal findings and experience form the basis for this article. RESULTS: Candida albicans is still the most common species causing invasive fungal infections, but Candida non-albicans species are increasing in number. Invasive Aspergillus infections and infection with other moulds than Aspergillus spp. do occur, but do not constitute a large proportion of these infections. As of today we have four classes of antifungal agents and seven drugs with different mechanisms of action are registered in Norway. Primary resistance to several of these drugs has been observed in a number of Candida and Aspergillus species and this is the dominating form of resistance we observe today. Secondary resistance due to treatment is still an uncommon finding. Clinical resistance, which, in spite of in vitro susceptibility does not lead to eradication of the fungus, is also commonly observed. INTERPRETATION: The incidence of natural resistant fungi is increasing. Our main current challenge is therefore to rapidly and precisely identify the fungi so the proper drug is used to quickly initiate treatment on the correct indication.
The impact of silver nanoparticles (NPs) and microparticles (MPs) on bacterial and fungal assemblages was studied in soils collected from a low arctic site. Two different concentrations (0.066% and 6.6%) of Ag NPs and Ag MPs were tested in microcosms that were exposed to temperatures mimicking a winter to summer transition. Toxicity was monitored by differential respiration, phospholipid fatty acid analysis, polymerase chain reaction-denaturing gradient gel electrophoresis and DNA sequencing. Notwithstanding the effect of Ag MPs, nanosilver had an obvious, additional impact on the microbial community, underscoring the importance of particle size in toxicity. This impact was evidenced by levels of differential respiration in 0.066% Ag NP-treated soil that were only half that of control soils, a decrease in signature bacterial fatty acids, and changes in both richness and evenness in bacterial and fungal DNA sequence assemblages. Prominent after Ag NP-treatment were Hypocreales fungi, which increased to 70%, from only 1% of fungal sequences under control conditions. Genera within this Order known for their antioxidant properties (Cordyceps/Isaria) dominated the fungal assemblage after NP addition. In contrast, sequences attributed to the nitrogen-fixing Rhizobiales bacteria appeared vulnerable to Ag NP-mediated toxicity. This combination of physiological, biochemical and molecular studies clearly demonstrate that Ag NPs can severely disrupt the natural seasonal progression of tundra assemblages.
Estimation of antioxidant, antimicrobial activity and brine shrimp toxicity of plants collected from Oymyakon region of the Republic of Sakha (Yakutia), Russia.
Several plants are reported to be produced various biological active compounds. Lichens from the extreme environments such as high altitude, high UV, drought and cold are believed to be synthesized unique types of secondary metabolites than the other one. Several human pathogenic bacteria and fungi have been muted into drug resistant strains. Various synthetic antioxidant compounds have posed carcinogenic effects. This phenomenon needs further research for new effective drugs of natural origin. This manuscript aimed to screen new source of biological active compounds from plants of subarctic origin.
A total of 114 plant species, including 80 species of higher plants, 19 species of lichens and 15 species of mosses, were collected from Oymyakon region of the Republic of Sakha (Yakutia), Russia (63?20'N, 141?42'E-63?15'N, 142?27'E). Antimicrobial, DPPH free radical scavenging and brine shrimp (Artemia salina) toxicity of all crude extract were evaluated. The obtained result was analyzed and compared with commercial standards. A total of 28 species of higher plants showed very strong antioxidant activity (DPPH IC50, 0.45-5.0 ?g/mL), 13 species showed strong activity (DPPH IC50, 5-10 ?g/mL), 22 species showed moderate antioxidant activity (DPPH IC50,10-20 ?g/mL) and 17 species showed weak antioxidant activity (DPPH IC50 more than 20 ?g/mL). Similarly, 3 species of lichen showed strong antioxidant activity, one species showed moderate and 15 species showed weak DPPH reducing activity. In addition, 4 species of mosses showed moderate antioxidant activity and 11 species showed weak antioxidant activity. Similarly, extracts of 51 species of higher plants showed antimicrobial (AM) activity against Staphylococcus aureus and 2 species showed AM activity against Candida albicans. Similarly, 11 species of lichen showed AM activity against S. aureus and 3 species showed AM activity against Escherichia coli. One species of moss showed AM activity against S. aureus. And finally, one species of higher plant Rheum compactum and one species of lichen Flavocetraria cucullata showed the toxicity against Brine shrimp larvae in 100 ?g/mL of concentration.
The experimental results showed that subarctic plant species could be potential sources of various biologically active natural compounds.
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Cites: Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7915-228367443
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, and Marine Biopharmaceutical Institute, Second Military Medical University, Shanghai 200433, China. yuhaobing1986@126.com.
Three new pimarane diterpenes, eutypellenoids A?C (1?3), together with a known compound, eutypenoid C (4), were isolated from the culture extract of Eutypella sp. D-1 derived from the Arctic region. Compounds 1?3 possessed an uncommon tetrahydrofuran-fused pimarane diterpene skeleton. The structures of all compounds were determined by detailed spectroscopic analysis, electronic circular dichroism (ECD) analysis, as well as a comparison with the literature data. Antibacterial, antifungal, and cytotoxic activities of these compounds were evaluated. Compound 2 displayed antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 8 and 8 µg/mL, respectively. Additionally, compound 2 showed antifungal activity against Candidaparapsilosis, Candida albicans, Candida glabrata, and Candida tropicalis with MIC values of 8, 8, 16, and 32 µg/mL, respectively. Furthermore, compound 2 exhibited moderate cytotoxic activity against HCT-116 cell line with IC50 value of 3.7 µM.
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Cites: Mar Drugs. 2016 Mar 07;14(3):null PMID 26959036
Cites: J Asian Nat Prod Res. 2018 Jun 18;:1-9 PMID 29911892
Cites: Bioorg Med Chem. 2005 Dec 15;13(24):6651-62 PMID 16140015
