Synthesis,Molecular Modeling,and Biological Evaluation of Novel Chiral Thiosemicarbazone Derivatives as Potent Anticancer Agents

A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF‐7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC‐27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound 17b exhibited the most potent activity (IC₅₀ 4.6 μM) against HGC‐27 as compared with the reference compound, sindaxel (IC₅₀ 10.3 μM), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents. Chirality 27:177–188, 2015. © 2014 Wiley Periodicals, Inc.     

The Effects of Chromium Picolinate and Chromium Histidinate Administration on NF-κB and Nrf2/HO-1 Pathway in the Brain of Diabetic Rats

The objective of this experiment was to investigate the effects of supplemental chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-??B p65) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in diabetic rat brain. Nondiabetic (n?=?45) and diabetic (n?=?45) male Wistar rats were either not supplemented or supplemented with CrPic or CrHis via drinking water to consume 8???g elemental chromium (Cr) per day for 12?weeks. Diabetes was induced by streptozotocin injection (40?mg/kg i.p., for 2?weeks) and maintained by high-fat feeding (40?%). Diabetes was associated with increases in cerebral NF-??B and 4-hydroxynonenal (4-HNE) protein adducts and decreased in cerebral nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (I??B??) and Nrf2 levels. Both Cr chelates were effective to decrease levels of NF-??B and 4-HNE protein adducts and to increase levels of I??B?? and Nrf2 in the brain of diabetic rats. However, responses of these increases and decreases were more notable when Cr was supplemented as CrHis than as CrPic. In conclusion, Cr may play a protective role in cerebral antioxidant defense system in diabetic subjects via the Nrf2 pathway by reducing inflammation through NF-??B p65 inhibition. Histidinate form of Cr was superior to picolinate form of Cr in reducing NF-??B expression and increasing Nrf2 expression in the brain of diabetic rats.     

The structure of 180° supernumerary limbs and a hypothesis of their formation

The results of a detailed analysis of 100 supernumerary limbs generated by 180° ipsilateral rotation (on the same limb stump) of regeneration blastemas is presented. The limbs were analyzed in terms of their position of origin, frequency, cartilage structure by Victoria blue staining, and muscle structure by serial sections. Single, double, or triple supernumeraries can be produced at no unique position of origin, although the posterodorsal quadrant was preferred. Four classes of supernumerary limbs were generated by such operations—normal; double dorsal or double ventral; part normal/part mirror imaged; part normal/part inverted in approximately equal frequencies. After amputation of these supernumeraries the same muscle patterns are faithfully regenerated. A hypothesis to explain the production of these abnormal limbs is proposed based on the observed phenomenon of fusion of supernumerary blastemata, but their regenerative behaviour presents problems for current models of pattern formation. Similar results have been obtained with developing limb buds and the relation between development and regeneration is discussed.     

Anti-HIV-1 activity of low molecular weight sulfated chitooligosaccharides

Chitooligosaccharides are nontoxic and water-soluble compounds obtained by enzymatic degradation of chitosan, which is derived from chitin by a deacetylation process. Chitooligosaccharides possess broad range of activities such as antitumour, antifungal, antibacterial activities. Sulfated chitooligosaccharides (SCOSs) with different molecular weights were synthesized by a random sulfation reaction. In the present study, anti-HIV-1 properties of SCOSs and the impact of molecular weight on their inhibitory activity were investigated. SCOS III (MW 3-5 kDa) was found to be the most effective compound to inhibit HIV-1 replication. At nontoxic concentrations, SCOS III exhibited remarkable inhibitory activities on HIV-1-induced syncytia formation (EC₅₀ 2.19 μg/ml), lytic effect (EC₅₀ 1.43 μg/ml), and p24 antigen production (EC₅₀ 4.33 μg/ml and 7.76 μg/ml for HIV-1_RF and HIV-1_Ba-L, respectively). In contrast, unsulfated chitooligosaccharides showed no activity against HIV-1. Furthermore, it was found that SCOS III blocked viral entry and virus-cell fusion probably via disrupting the binding of HIV-1 gp120 to CD4 cell surface receptor. These results suggest that sulfated chitooligosaccharides represent novel candidates for the development of anti-HIV-1 agent.     

Possible role of adenosine in the CNS effects of ethanol

The ability of adenosine to modify the CNS effects of acute and chronic ethanol was studied by using theophylline, an adenosine antagonist, and dipyridamole, a blocker of adenosine reuptake. We also studied the binding characteristics of adenosine using crude membranes of whole brain. Theophylline pretreatment prior to acute ethanol administration markedly reduced the duration of ethanol-induced sleep and similarly decreased the intensity and duration of motor incoordination. In chronic ethanol treated mice the effect of theophylline on ethanol-induced hypnosis and motor incoordination was similar to the acute experiment. Dipyridamole markedly prolonged the duration of ethanol-induced hypnosis and potentiated the motor incoordination produced by acute ethanol. However, in chronic ethanol treated mice dipyridamole was not able to potentiate the motor incoordinating effect of ethanol although it was able to prolong ethanol hypnosis similar to the results obtained in the acute ethanol study. Neither drug had any effect on ethanol-induced hypothermia, in either the acute or chronic studies.After 10 days of ethanol ingestion the adenosine dissociation constant was unchanged whereas the number of brain adenosine receptors was increased 28% although the increase did not reach statistical significance. The number of the adenosine receoptors was reduced 40% at 24 and 48 h after withdrawal and returned to prewithdrawal levels at 72 h. The dissociation constant was reduced at 24 and 48 h but by 72 h had returned to prewithdrawal levels. The marked changes in adenosine binding characteristics as well as the modification of some CNS effect of ethanol by drugs which influence either adenosine binding to its receptor or the availability of adenosine suggest that adenosine may be involved in the expression of some of the CNS effects of ethanol.     

Diversity and metabolic potential of culturable bacteria from the rhizosphere of Turkish tea grown in acidic soils

The purpose of this study was to investigate the diversity of cultivable phosphate solubilising (PSB) and total bacteria originated from 384 rhizospheric acidic soils samples of tea plants grown at 32 locations. Over 900 rhizoplane bacteria were randomly selected from agar-solidified trypticase soy broth, and identified using fatty acid methyl ester (FAME) profiles. Based on FAME profiles, 53 bacterial genera were identified with a similarity index >0.3, but 60.3% of the identified isolates belonged to five genera: Bacillus (34.6%), Pseudomonas (8.9%), Stenotrophomonas (6.1%), Paenibacillus (5.9%) and Arthrobacter (4.8%). The bacilli group comprised many different species, with the most abundant being B. cereus, B. megaterium and B. sphaericus. The main identified Pseudomonads included P. fluorescens, P. putida, and P. alcaligenes. About 30.4% of the bacterial isolates could not be classified to genus since their similarity indices were <0.3 indicating no close matches. Most of the total and P-solubilizing bacteria isolated were Gram positive (61.3 and 52.3%), and Gram negative constituted only 38.7 and 47.7%. Out of the 214 PSB from a pool of 506 bacterial isolates recovered on the selective media from the rhizosphere of tea, 74 of them were characterized by carbon sources using BIOLOG^M GN2 and GP2 plates. Bacillus, Pseudomonas, Paenibacillus and Stenotrophomonas genera were the most prominent P-solubilizing groups in the rhizosphere and soil populations analyzed. B. cereus, P. fluorescens, S. maltophilia, B. megaterium, P. putida, B. sphaericus and Paenibacillus polymyxa were the most frequent P-solubilizing species in the acidic tea rhizosohere soils. Selected Gram-positive PSB appeared to favour carbohydrates, and Gram-negative bacteria appeared to favour carboxylic acids, amino acids and carbohydrates as carbon sources. Selected phosphate solubilizing acid tolerant strains showed high variability in utilizing various carbon sources.     

Combined point mutations in codon 12 and 13 of KRAS oncogene in prostate carcinomas

Prostate cancer is a common malignancy that develops by structural mutation(s) and/or other genetic alterations in specific genes.The G to T transversions in codon 12 and C to T transitions in codon 13 of KRAS proto-oncogene are predominant point mutations that occur in about 20% of different cancers in human. In the current study it was aimed to investigate the prevalence and predictive significance of KRAS mutations in patients with prostate carcinomas. In a total of 30 fresh tumoural tissue specimens were investigated in patients with prostate carcinoma. All tumoural specimens were histo-pathologically diagnosed and genotyped for codon 12, 13 KRAS point mutations by reverse hybridisation and direct sequencing methods. KRAS mutations were found in 12 (40%) samples with 29 samples deriving from adenocarcinomas and 1 sample was small cell prostate carcinoma. In 1 (3.44%) sample codon 12 was found to be mutated and in 2 (6.8%) samples codon 13 and in 9 (31%) samples combined codon 12 and 13 were found to be mutated particularly in higher grade of tumoural tissues. Our study, based on representative collection of human prostate tumours, indicates that combined mutations in codons 12 and 13 KRAS are relatively infrequent and most commonly occur in prostate carcinomas.     

Investigation of the Effects of the Fenoxaprop-p-Ethyl Herbicide and Salicylic Acid on the Ascorbic Acid and Vitamin B6 Vitamers in Wheat Leaves

Journal of Plant Growth Regulation - Herbicides inhibit plant growth and development by various mechanisms, and oxidative stress is a common plant response to herbicide treatment. In a limited...