The mode of action of cytotoxic and antitumor 1-nitroacridines. I. The 1-nitroacridines do not exert their cytotoxic effects by physicochemical binding with DNA

The mode of action of cytotoxic and antitumor 1-nitroacridines and their isomeric derivatives was studied by comparing their effects in cell-free systems and towards cultured tumor HeLa cells, assuming that the nitroacridines considered exert cytotoxic effects by physicochemical binding with the DNA. All the nitroacridines impaired biosyntheses of DNA, RNA and protein in cultured HeLa cells and a causal relationship between nitroacridine inhibition of macromolecular biosyntheses and lethal effects of the agents appears likely. In cell-free systems, the nitroacridines bound with two independent sites on the DNA, forming complexes with enhanced resistance to DNA strand separation upon melting and inhibited the DNA polymerase reaction by altering activity of template and/or of enzyme. The 1-nitroacridines were poorly effective in cell-free systems and were the most potent inhibitors toward the growth of HeLa cells among the derivatives studied. It is concluded that the primary events responsible for cytotoxic effects of antitumor 1-nitroacridines and of their isomeric derivatives are different. The metabolic activation of 1-nitroacridines to more reactive intermediates which will attach to and alter the structure and/or function of DNA of sensitive cells is suggested.     

In silico annotation of unreviewed acetylcholinesterase (AChE) in some lepidopteran insect pest species reveals the causes of insecticide resistance

Lepidoptera is the second most diverse insect order outnumbered only by the Coeleptera. Acetylcholinesterase (AChE) is the major target site for insecticides. Extensive use of insecticides, to inhibit the function of this enzyme, have resulted in the development of insecticide resistance. Complete knowledge of the target proteins is very important to know the cause of resistance. Computational annotation of insect acetylcholinesterase can be helpful for the characterization of this important protein. Acetylcholinesterase of fourteen lepidopteran insect pest species was annotated by using different bioinformatics tools. AChE in all the species was hydrophilic and thermostable. All the species showed lower values for instability index except L. orbonalis, S. exigua and T. absoluta. Highest percentage of Arg, Asp, Asn, Gln and Cys were recorded in P. rapae. High percentage of Cys and Gln might be reason for insecticide resistance development in P. rapae. Phylogenetic analysis revealed the AChE in T. absoluta, L. orbonalis and S. exigua are closely related and emerged from same primary branch. Three functional motifs were predicted in eleven species while only two were found in L. orbonalis, S. exigua and T. absoluta. AChE in eleven species followed secretory pathway and have signal peptides. No signal peptides were predicted for S. exigua, L. orbonalis and T. absoluta and follow non secretory pathway. Arginine methylation and cysteine palmotylation was found in all species except S. exigua, L. orbonalis and T. absoluta. Glycosylphosphatidylinositol (GPI) anchor was predicted in only nine species.     

Quantitative structure-activity relationship study of novel rhinacanthins and related naphthoquinone esters as anticancer agents

Abstract

GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC₅₀ values (13 and 12?nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC_0–2h at the dose of 30?mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction).     

Structure and physicochemical properties of starches from kidney bean seeds at immature,premature and mature stages of development

Starches from kidney bean (Phaseolus vulgaris L. cv. Toramame) seeds at the immature, premature, mature stages of development were examined. The starch content increased from 94, 219 to 265 mg per seed. Starches showed the C(a)-crystalline type composed of small (<5 micrometer) and large (10-35 micrometer) granules, with the large granules largely increasing with maturity. The amylose content increased from 21, 26 to 27%, and rapid viscograms and DSC thermograms suggested that the mature-stage starch was gelatinized with ease. The amylose increased in size from DPn 820, 1000 to 1080 and a number of chains per molecule (NC) from 3.3, 4.2 to 4.5. The branched amylose was a minor component (11-18% by mole) with NC 20-22. The amylopectin was similar in CL (23), beta-amylolysis limit (59%), and chain-length distribution, but reduced in size (DPn 17,100-5270) and increased in content of phosphorus (114-174 ppm) with an increase in the amount of phosphorus linked to C-6 of the glucose residue (8-66%).     

箬叶多糖的分离纯化及其理化性质的研究

采用分步提取的方式从中药箬叶中分离得到８种多糖组分：酸性杂多糖ＦＳ、ＦＥ、ＦⅠ,β－Ｄ－葡萄糖醛酸聚糖ＦⅡ和四种半纤维素多糖α－Ｄ－木聚糖ＦⅢ－ａ、ＦⅢ－ｂ、ＦⅣ－ａ及ＦⅣ－ｂ．紫外光谱、红外光谱、凝胶色谱、元素分析等结果表明８种箬叶多糖为纯品．并采用纸层析,气相色谱分析确定其单糖组成．采用高效凝胶渗透色谱ＧＰＣ法测定了４种箬叶多糖ＦＥ、ＦⅠ、ＦⅢ－ａ及ＦⅣ－ａ的重均分子量Ｍｗ、数均分子量Ｍｎ,均为大分子,分子量分布较窄,纯度较高．     

Influence of pyrolysis condition on switchgrass bio-oil yield and physicochemical properties

The poor and inconsistent physicochemical properties of bio-oil are inhibiting its industrialized production. We investigated the variability in properties of switchgrass bio-oil produced at three pyrolysis temperatures (T = 450, 500, and 550 °C) and three feedstock moisture contents (MC = 5%, 10%, and 15%) in a 3 × 3 factorial experiment in order to exploit opportunities to improve bio-oil properties through optimization of pyrolysis parameters. Results showed that even with the single type of feedstock and pyrolysis system, the two main factors and their interaction caused large variations in bio-oil yield and most of the measured physicochemical properties. Following improvements of bio-oil properties could be individually achieved by selecting an optimal pyrolysis condition (shown in parenthesis) comparing with the worst case: increase of bio-oil yield by more than twofold (MC = 10%, T = 450 °C), increase of pH by 20.4% from 2.74 to 3.3 (MC = 10%, T = 550 °C), increase of higher heating value by 18.1% from 16.6 to 19.6 MJ/kg (MC = 10%, T = 450 °C), decrease of density by 5.9% from 1.18 to 1.11 g/cm³ (MC = 5%, T = 550 °C), decrease of water content by 36% from 31.4 to 20.1 wt.% (MC = 5%, T = 450 °C), decrease of viscosity by 40% from 28.2 to 17 centistokes (MC = 5%, T = 550 °C), decrease of solid content by 57% from 2.86 to 1.23 wt.% (MC = 15%, T = 550 °C), and decrease of ash content by 41.9% from 0.62 to 0.36 wt.% (MC = 15%, T = 550 °C). There is no single, clear-cut optimal condition that can satisfy the criteria for a bio-oil product with all the desired properties. Trade-offs should be balanced according to the usage of the end-products.     

Physicochemical characterization and functional analysis of some snake venom toxin proteins and related non-toxin proteins of other chordates

Snake venom contains a diverse array of proteins and polypeptides. Cytotoxins and short neurotoxins are non-enzymatic polypeptide components of snake venom. The three-dimensional structure of cytotoxin and short neurotoxin resembles a three finger appearance of three-finger protein super family. Different family members of three-finger protein super family are employed in diverse biological functions. In this work we analyzed the cytotoxin, short neurotoxin and related non-toxin proteins of other chordates in terms of functional analysis, amino acid compositional (%) profile, number of amino acids, molecular weight, theoretical isoelectric point (pI), number of positively charged and negatively charged amino acid residues, instability index and grand average of hydropathy with the help of different bioinformatical tools. Among all interesting results, profile of amino acid composition (%) depicts that all sequences contain a conserved cysteine amount but differential amount of different amino acid residues which have a family specific pattern. Involvement in different biological functions is one of the driving forces which contribute the vivid amino acid composition profile of these proteins. Different biological system dependent adaptation gives the birth of enriched bio-molecules. Understanding of physicochemical properties of these proteins will help to generate medicinally important therapeutic molecules for betterment of human lives.     

核盘菌多糖的理化性质

核盘菌多糖(SSG)是由核盘菌(Sclerotinia sclerotiorum)通过深层发酵产生的一种胞外多糖,具有潜在的免疫调节活力和明显的抑瘤作用。研究表明,SSG是一种由β-配糖键连接的葡聚糖。在水中溶解缓慢,但粘度较高,并具有良好的流变学性质。其特性粘度几乎不随离子强度的变化而改变,在pH1.88—12.26之间,[η]值变化不显著,但当pH值为13.32时,由于分子构象的变化导致[η]值急骤下降。温度≤90℃和热处理对SSG溶液的表观粘度影响不大。     

Banana starch: production, physicochemical properties, and digestibility—a review

The large quantity of green cull bananas has the potential of being used industrially and, thereby, to improve banana economics and eliminate the large environmental problem presented by banana waste. This review summarizes the present knowledge of the composition, structure, physiochemical properties, modifications, and digestibility of banana starches and provides suggestions for needed research to improve the utilization of green cull bananas.