Synthesis and antitumor activity of some novel thiophene, pyrimidine, coumarin, pyrazole and pyridine derivatives

2-Cyano-N-(thiazol-2-yl) acetamide (2a) and 2-cyano-N-(oxazol-2-yl) acetamide (2b) were obtained via the reaction of ethylcyanoacetate with either 2-aminothiazole (1a) or 2-aminooxazole (1b). The the formed products were directed toward the reaction with cyclopentanone and elemental sulphur in the presence of triethylamine to give cyclopenta[b]thiophene derivatives (3a,b). The latter products when reacted with either ethylcyanoacetate or malononitrile to form compounds 4a,b and 5a,b, respectively. Compounds 4a,b were aimed to synthesize some heterocyclic compounds; thus internal cyclization reactions were introduced to form compounds 6a,b. Also, compounds 4a,b reacted with salicylaldehyde, hydrazine derivatives and either urea or thiourea to produce coumarin derivatives (7a,b), pyrazole derivatives (8a-d) and pyrimidine derivatives (9a-d), respectively. Reaction of either benzaldehyde or benzene diazonium chloride (11) with compounds 4a,b afforded compounds 10a,b and 12a,b, respectively. On the other hand, compounds 5a,b underwent internal cyclization to form pyrimidine derivatives 13a,b. Also when compounds 5a,b reacted with either ethylcyanoacetate or malononitrile they gave pyridine derivatives (15a-d) through the formation of intermediates (14a-d). Finally, formation of fused pyrimidine derivatives (17a,b) was afforded through the reaction of compounds 5a,b and salicylaldehyde, applying two different pathways. First pathway used catalytic amount of piperidine to form compounds 16a,b; the latter products underwent cyclization to give compounds 17a,b. The second pathway using catalytic amount of sodium ethoxide solution directly in one step afforded compounds 17a,b. The structures of the newly synthesized compounds were established using IR, 1H NMR, 13C NMR and mass spectrometry and their antitumor activity was investigated. Some of these compounds showed promising inhibitory effects on the three different cell lines. However, fused pyrimidine acetonitrile derivatives 6a and 6b exerted the highest inhibitory effect comparable to that of doxorubicin

Animal and plant protein intake during infancy and childhood DNA methylation:a meta-analysis in the NutriPROGRAM consortium

Background: Higher early-life animal protein intake is associated with a higher childhood obesity risk compared to plant protein intake. Differential DNA methylation may represent an underlying mechanism. Methods: We analysed associations of infant animal and plant protein intakes with DNA methylation in early (2−6 years, N = 579) and late (7̄−12 years, N = 604) childhood in two studies. Study-specific robust linear regression models adjusted for relevant confounders were run, and then meta-analysed using a fixed-effects model. We also performed sex-stratified meta-analyses. Follow-up analyses included pathway analysis and eQTM look-up. Results: Infant animal protein intake was not associated with DNA methylation in early childhood, but was associated with late-childhood DNA methylation at cg21300373 (P = 4.27 × 10¯8, MARCHF1) and cg10633363 (P = 1.09 × 10¯7, HOXB9) after FDR correction. Infant plant protein intake was associated with early-childhood DNA methylation at cg25973293 (P = 2.26 × 10−7, C1orf159) and cg15407373 (P = 2.13 × 10−7, MBP) after FDR correction. There was no overlap between the findings from the animal and plant protein analyses. We did not find enriched functional pathways at either time point using CpGs associated with animal and plant protein. These CpGs were not previously associated with childhood gene expression. Sex-stratified meta-analyses showed sex-specific DNA methylation associations for both animal and plant protein intake. Conclusion: Infant animal protein intake was associated with DNA methylation at two CpGs in late childhood. Infant plant protein intake was associated with DNA methylation in early childhood at two CpGs. A potential mediating role of DNA methylation at these CpGs between infant protein intake and health outcomes requires further investigation.</p

Performance Analysis of Solar Adsorption Cooling System - Effect of Position of Heat Storage Tank

An insulated storage tank has been added with adsorption cooling system run by solar heat collected by CPC panel. It has been expected and seen that the storage tank has a vital contribution in the performance of the chiller. The storage tank is connected with a solar heat driven single stage two bed basic adsorption chillers activated with silica gel-water pair in two ways. The tank is connected in such a way that (i) the solar collectors supply hot water to the desorption bed, the outflow of the desorber is collected in the reserve tank. The reserve tank supplies water to the collector and complete the heat transfer cycle. (ii) The solar collector supply hot water which is collected in the storage tank first and then supplied to the desorber. The outflow of the desorber is carried to the collector again. Comparative studies have been conducted at the steady state for both of the systems with heat storage. It has been observed that the system is robust with design (i) while with design (ii) performance enhances beyond the sunset time with heat storage

Expression of auxin-binding protein1 during plum fruit ontogeny supports the potential role of auxin in initiating and enhancing climacteric ripening

Auxin-binding protein1 (ABP1) is an active element involved in auxin signaling and plays critical roles in auxin-mediated plant development. Here, we report the isolation and characterization of a putative sequence from Prunus salicina L., designated PslABP1. The expected protein exhibits a similar molecular structure to that of well-characterized maize-ABP1; however, PslABP1 displays more sequence polarity in the active-binding site due to substitution of some crucial amino-acid residues predicted to be involved in auxin-binding. Further, PslABP1 expression was assessed throughout fruit ontogeny to determine its role in fruit development. Comparing the expression data with the physiological aspects that characterize fruit-development stages indicates that PslABP1 up-regulation is usually associated with the signature events that are triggered in an auxin-dependent manner such as floral induction, fruit initiation, embryogenesis, and cell division and elongation. However, the diversity in PslABP1 expression profile during the ripening process of early and late plum cultivars seems to be due to the variability of endogenous auxin levels among the two cultivars, which consequently can change the levels of autocatalytic ethylene available for the fruit to co-ordinate ripening. The effect of auxin on stimulating ethylene production and in regulating PslABP1 was investigated. Our data suggest that auxin is involved in the transition of the mature green fruit into the ripening phase and in enhancing the ripening process in both auxin- and ethylene-dependent manners thereafter

Two highly divergent alcohol dehydrogenases of melon exhibit fruit ripening-specific expression and distinct biochemical characteristics

Alcohol dehydrogenases (ADH) participate in the biosynthetic pathway of aroma volatiles in fruit by interconverting aldehydes to alcohols and providing substrates for the formation of esters. Two highly divergent ADH genes (15% identity at the amino acid level) of Cantaloupe Charentais melon (Cucumis melo var. Cantalupensis) have been isolated. Cm-ADH1 belongs to the medium-chain zinc-binding type of ADHs and is highly similar to all ADH genes expressed in fruit isolated so far. Cm-ADH2 belongs to the short-chain type of ADHs. The two encoded proteins are enzymatically active upon expression in yeast. Cm-ADH1 has strong preference for NAPDH as a co-factor, whereas Cm-ADH2 preferentially uses NADH. Both Cm-ADH proteins are much more active as reductases with Kms 10–20 times lower for the conversion of aldehydes to alcohols than for the dehydrogenation of alcohols to aldehydes. They both show strong preference for aliphatic aldehydes but Cm-ADH1 is capable of reducing branched aldehydes such as 3-methylbutyraldehyde, whereas Cm-ADH2 cannot. Both Cm-ADH genes are expressed specifically in fruit and up-regulated during ripening. Gene expression as well as total ADH activity are strongly inhibited in antisense ACC oxidase melons and in melon fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. These data suggest that each of the Cm-ADH protein plays a specific role in the regulation of aroma biosynthesis in melon fruit

The prognostic significance of minimal residual disease in adult Egyptian patients with precursor acute lymphoblastic leukemia

AbstractBackgroundMinimal residual disease (MRD) studies in adult acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of relapse.ObjectivesWe aimed to determine the value of MRD monitoring by flowcytometry (FCM) in predicting outcome in adult Precursor ALL patients.Patients and methodsBone marrow (BM) samples were analyzed by 4-color FCM collected at diagnosis and after induction therapy (MRD1) to correlate MRD positivity with disease free survival (DFS) and overall survival (OS).ResultsStudy included 57 adult ALL patients (44 males and 13 females) with a median age of 22years (18–49). DFS showed no significant difference with age, gender and initial TLC (p=0.838, 0.888 and 0.743, respectively). Cumulative DFS at 2years was 34% for B-lineage ALL (n: 35) and 57% for T-lineage ALL (n: 18) (p=0.057). Cumulative DFS at 2years was 7% for MRD1 positive (high risk, HR) versus 57% for MRD1 negative patients (Low risk, LR) (p<0.001). Cumulative DFS at 2years was 29% for HR patients (n: 26) versus 55% for LR (n: 27) according to GMALL classification (p=0.064). Cumulative OS did not differ according to age, gender and TLC (p=0.526, 0.594 and 0.513, respectively). Cumulative OS at 2years was 36% for B ALL (n: 39) versus 77% for TALL (n: 18) (p=0.016) and was 49% for Philadelphia chromosome (Ph) negative patients versus 0% for Ph-positive patients (p<0.001). Regarding MRD1, OS at 2years was 18% for MRD1 HR (n: 17) versus 65% for MRD1 LR (n: 38) (p<0.001). OS was 35% for high-risk patients (n: 30) and 62% for low-risk patients (n: 27) classified according to GMALL risk stratification (p=0.017).ConclusionMRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients

Performance evaluation of a waste-heat driven adsorption system for automotive air-conditioning: Part II - Performance optimization under different real driving conditions

[EN] In this part, Part 11, of a two-part study, the validated model of part I is integrated into a general vehicle model in order to predict the performance of the system under real driving conditions. The overall model takes into account all the system components to simulate the dynamic performance of the entire system and predict the cabin temperature at the available waste heat. The system was implemented in a Fiat Grande Punto vehicle and the experimental tests were performed at the Centro Ricerche Fiat (CRF), Italy laboratories. Different design configurations were investigated to explore further improvements of the performance. Results showed that the model was able to well predict the transient performance of the system under different start-up and ambient conditions as well as the normal operating conditions. Using two radiators instead of one radiator increases the cooling capacity by 7.0% and decreases the cabin temperature by 9.1%. At the warming up period, the adsorption system faces serious difficulties to start producing the required cooling. Possible strategies to avoid this problem were studied and compared. In general, it has been proved that the amount of engine waste heat available is sufficient to produce enough cooling to keep reasonably comfortable temperatures in the cabin. (C) 2016 Elsevier Ltd. All rights reserved.This work has been partially supported by the Thermally Operated Mobile Air Conditioning Systems (TOPMACS). The authors are very grateful to the Energy Research Center of Netherlands (ECN) for their support with the experimental work.This work has been partially supported by the Thermally Operated Mobile Air Conditioning Systems (TOPMACS). The authors are very grateful to the Energy Research Center of Netherlands (ECN) for their support in the experimental work.Verde Trindade, M.; Harby Mohamed Abd Alaal, K.; De Boer, R.; Corberán, JM. (2016). Performance evaluation of a waste-heat driven adsorption system for automotive air-conditioning: Part II - Performance optimization under different real driving conditions. Energy. 115:996-1009. doi:10.1016/j.energy.2016.09.086S996100911

Reakcija β-amino-α,γ-dicianokrotononitrila s acetofenonom: sinteza derivata piridina, piridazina i tiofena s antimikrobnim djelovanjem

Condensation of β-amino-α,γ-dicyanocrotononitrile (1) with acetophenone gave the 2-amino-4-phenylpenta-1,3-diene-1,1,3-tricarbonitrile (2). The latter product was used in a series of heterocyclization reactions when react with different reagents like diazonium salts, hydrazines, hydroxylamine and elemental sulfur to give pyridazine, pyrazole, isoxazole and thiophene derivatives, respectively. On the other hand, it gave pyridine derivatives with aromatic aldehydes followed by reaction with cyanomethylene reagents. The MIC values for the newly synthesized product were measured against E. coli, B. cereus, B. subtilis and C. albicansKondenzacijom β-amino-α,γ-dicijanokrotononitrila 1 s acetofenonom dobiven je 2-amino-4-fenilpenta-1,3-dien-1,1,3-trikarbonitril (2) koji je upotrebljen u reakcijama heterociklizacije s različitim reagensima poput diazonijevih soli, hidrazina, hidroksilamina i elementarnog sumpora pri čemu su nastali derivati piridazina, pirazola, izoksazola, odnosno tiofena. Spoj 2 je u reakciji s aromatskim aldehidima te naknadno sa cijanometilenima dao derivate piridina. Određene su MIC vrijednosti za novosintetizirane spojeve protiv E. coli, B. cereus, B. subtilis i C. albicans

Domestication syndrome is investigated by proteomic analysis between cultivated cassava (Manihot esculenta Crantz) and its wild relatives

Cassava (Manihot esculenta Crantz) wild relatives remain a largely untapped potential for genetic improvement. However, the domestication syndrome phenomena from wild species to cultivated cassava remain poorly understood. The analysis of leaf anatomy and photosynthetic activity showed significantly different between cassava cultivars SC205, SC8 and wild relative M. esculenta ssp. Flabellifolia (W14). The dry matter, starch and amylose contents in the storage roots of cassava cultivars were significantly more than that in wild species. In order to further reveal the differences in photosynthesis and starch accumulation of cultivars and wild species, the globally differential proteins between cassava SC205, SC8 and W14 were analyzed using 2-DE in combination with MALDI-TOF tandem mass spectrometry. A total of 175 and 304 proteins in leaves and storage roots were identified, respectively. Of these, 122 and 127 common proteins in leaves and storage roots were detected in SC205, SC8 and W14, respectively. There were 11, 2 and 2 unique proteins in leaves, as well as 58, 9 and 12 unique proteins in storage roots for W14, SC205 and SC8, respectively, indicating proteomic changes in leaves and storage roots between cultivated cassava and its wild relatives. These proteins and their differential regulation across plants of contrasting leaf morphology, leaf anatomy pattern and photosynthetic related parameters and starch content could contribute to the footprinting of cassava domestication syndrome. We conclude that these global protein data would be of great value to detect the key gene groups related to cassava selection in the domestication syndrome phenomena

HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons

Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2. © 2013 Zhang et al