Involvement of a coumarin analog AD-013 in the DNA damage response pathways in MCF-7 cells

Molecular Biology Reports - Coumarin is a plant-derived compound but as such has no medical uses. Several synthetic coumarin analogs have been shown to possess anti-proliferative activity and to...     

Synthesis,characterization and evaluation of antimicrobial and cytotoxic activities of biogenic silver nanoparticles synthesized from <Emphasis Type="Italic">Streptomyces xinghaiensis</Emphasis> OF1 strain

We report synthesis of silver nanoparticles (AgNPs) from Streptomyces xinghaiensis OF1 strain, which were characterised by UV–Vis and Fourier transform infrared spectroscopy, Zeta sizer, Nano tracking analyser, and Transmission electron microscopy. The antimicrobial activity of AgNPs alone, and in combination with antibiotics was evaluated against bacteria, namely Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis, and yeasts viz., Candida albicans and Malassezia furfur by using micro-dilution method. The minimum inhibitory concentration (MIC) and minimum biocidal concentration of AgNPs against bacterial and yeast strains were determined. Synergistic effect of AgNPs in combination with antibacterial and antifungal antibiotics was determined by FIC index. In addition, MTT assay was performed to study cytotoxicity of AgNPs alone and in combination with antibiotics against mouse fibroblasts and HeLa cell line. Biogenic AgNPs were stable, spherical, small, polydispersed and capped with organic compounds. The variable antimicrobial activity of AgNPs was observed against tested bacteria and yeasts. The lowest MIC (16 µg ml^?1) of AgNPs was found against P. aeruginosa, followed by C. albicans and M. furfur (both 32 µg ml^?1), B. subtilis and E. coli (both 64 µg ml^?1), and then S. aureus and Klebsiella pneumoniae (256 µg ml^?1). The high synergistic effect of antibiotics in combination with AgNPs against tested strains was found. The in vitro cytotoxicity of AgNPs against mouse fibroblasts and cancer HeLa cell lines revealed a dose dependent potential. The IC₅₀ value of AgNPs was found in concentrations of 4 and 3.8 µg ml^?1, respectively. Combination of AgNPs and antibiotics significantly decreased concentrations of both antimicrobials used and retained their high antibacterial and antifungal activity. The synthesis of AgNPs using S. xinghaiensis OF1 strain is an eco-friendly, cheap and nontoxic method. The antimicrobial activity of AgNPs could result from their small size. Remarkable synergistic effect of antibiotics and AgNPs offer their valuable potential in nanomedicine for clinical application as a combined therapy in the future.     

Novel (S)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12(2H,11H)-dione derivatives: Selective inhibition of MV-4-11 biphenotypic B myelomonocytic leukemia cells’ growth is accompanied by reactive oxygen species overproduction and apoptosis

A series of optically pure (R)- and (S)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12(2H,11H)-dione derivatives was designed and synthesized as novel anthramycin analogues in a three-step, one-pot procedure, and tested for their antiproliferative activity on nine following cell lines: MV-4-11, UMUC-3, MDA-MB-231, MCF7, LoVo, HT-29, A-549, A2780 and BALB/3T3. The key structural features responsible for exhibition of cytotoxic effect were determined: the (S)-configuration of chiral center and the presence of hydrophobic 4-biphenyl substituent in the side chain. Introduction of bromine atom into the 8 position (8g) or substitution of dilactam ring with benzyl group (8m) further improved the activity and selectivity of investigated compounds. Among others, compound 8g exhibited selective cytotoxic effect against MV-4-11 (IC₅₀?=?8.7?μM) and HT-29 (IC₅₀?=?17.8?μM) cell lines, while 8m showed noticeable anticancer activity against MV-4-11 (IC₅₀?=?10.8?μM) and LoVo (IC₅₀?=?11.0?μM) cell lines. The cell cycle arrest in G₁/S checkpoint and apoptosis associated with overproduction of reactive oxygen species was also observed for 8e and 8m.     

Investigating Niche Construction in Dynamic Human-Animal Landscapes: Bridging Ecological and Evolutionary Timescales

Human influence on the environment is evident at all landscape and ecological scales, from local to global, shaping both abiotic and biotic processes. Niche construction theory provides a means by which to investigate the consequences of these anthropogenic effects, but primatological research has been slow to integrate ecological and evolutionary timelines. We review methods that can be used to study how human niche construction influences nonhuman primates including phenological assessment, nonhuman primate behavioral observations, and ethnographic interview techniques. We argue that this approach provides a starting place to examine niche construction theory but that scholars of primate behavioral ecology must expand our methodologies to bridge the disconnect between ecological and evolutionary research time frames. We suggest areas of research and methods that have been underused but offer opportunities for integrative, innovative research. We conclude that an integrated, synthetic methodological approach is a major goal and that it will likely require a cross-disciplinary, collaborative effort.     

Cytotoxic and NF-κB and mitochondrial transmembrane potential inhibitory pentacyclic triterpenoids from Syzygium corticosum and their semi-synthetic derivatives

Syzygium is a large genus of flowering plants, with several species, including the clove tree, used as important resources in the food and pharmaceutical industries. In our continuing search for anticancer agents from higher plants, a chloroform extract of the leaves and twigs of Syzygium corticosum collected in Vietnam was found to be active toward the HT-29 human colon cancer cell line. Separation of this extract guided by HT-29 cells and nuclear factor-kappa B (NF-κB) inhibition yielded 19 known natural products, including seven triterpenoids, three ellagic acid derivatives, two methylated flavonoids, a cyclohexanone, four megastigmanes, a small lactone, and an aromatic aldehyde. The full stereochemistry of (+)-fouquierol (2) was defined for the first time. Biological investigations showed that (+)-ursolic acid (1) is the major cytotoxic component of S. corticosum, which exhibited also potent activities in the NF-κB and mitochondrial transmembrane potential (MTP) inhibition assays conducted, with IC₅₀ values of 31?nM and 3.5?µM, respectively. Several analogues of (+)-ursolic acid (1) were synthesized, and a preliminary structure-activity relationship (SAR) study indicated that the C-3 hydroxy and C-28 carboxylic acid groups and 19,20-dimethyl substitution are all essential in the mediation of the bioactivities observed for this triterpenoid.     

PATTERNS OF RELATIVE GROWTH IN NEREOCYSTIS LUETKEANA (PHAEOPHYTA)1

Plants of Nereocystis luetkeana (Mert.) Post. et Rupr. of different sizes were held on a raft at the surface of the sea off the Friday Harbor Laboratories, San Juan Island, Washington for 5 day periods for observation of detailed relative growth of different parts. Each stipe was marked at intervals with injected Indian ink and each blade was punched with a series of holes. Measurements of diameter, length, width and thickness were made before and after the 5 day periods. Blades showed a very similar pattern of relative growth rate (R) over an 18-fold range of sizes. The maximum local R in length was about 0.2 day⁻¹ and occurred at 6.5% of the distance from the bulb to the tip, declining to 0.01 at half way. Half the linear growth occurred in the proximal one tenth of the blade and 95% within the proximal half. The relative growth rate of the whole blade declined only slightly with increased size and lay between 0.0.3 and 0.06 day⁻¹ (approx. 3–6% day⁻¹). The linear growth rate therefore increased with blade size, the maximum observed being 14 cm day⁻¹. The maximum relative growth rate in blade width was slower, and sited more distally than that in length. Unless fertile tissue was involved all blade tissue, except that closely adjoining the bulb, became thinner during growth. R in volume reached 0.3 day⁻¹. Presumably because the plants were held near the sea surface stipes grew slowly, with a maximum linear rate of 9 mm day⁻¹. The maximum R in length decreased with stipe length. Bulb R in volume also decreased as size increased, from a maximum of 0.3 day⁻¹.