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https://www.readbyqxmd.com/read/30102466/6-chloropurine-ribonucleosides-from-chloropyrimidines-one-pot-synthesis
#1
Renaud Zelli, Waël Zeinyeh, Jean-Luc Décout
A one-pot glycosylation and cyclization procedure is described for the synthesis of 6-chloropurine ribonucleosides from chloropyrimidines. From such a procedure and modification of the obtained chloropurine ribonucleosides, many drug candidates or molecular tools for biological study designed from their similarity to naturally occurring nucleosides could be obtained. The synthesis begins by preparation of several amidinoaminochloropyrimidines as precursors for the one-pot procedure. Then, by adding trimethylsilyl trifluoromethanesulfonate (TMSOTf) to a mixture of a pyrimidine and 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribose, different 6-chloropurine ribonucleosides are obtained...
August 13, 2018: Current Protocols in Nucleic Acid Chemistry
https://www.readbyqxmd.com/read/30101366/d-ribose-induces-nephropathy-through-rage-dependent-nf-%C3%AE%C2%BAb-inflammation
#2
Jinni Hong, Xuemei Wang, Ning Zhang, Hong Fu, Weiwei Li
Recently, aberrantly high levels of D-ribose have been discovered in type II diabetic patients. D-ribose glycates proteins more rapidly than D-glucose, resulting in the production of advanced glycation end products (AGEs). Accumulations of these products can be found in impaired renal function, but the mechanisms are poorly understood. The present study tested whether D-ribose induces renal dysfunction via the RAGE-dependent NF-κB signaling pathway. In vivo, administration of D-ribose was found to lower blood glucose and regulate insulin tolerance...
August 13, 2018: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/30095186/global-metabolomic-responses-in-urine-from-atm-deficient-mice-in-response-to-ld-50-30-gamma-irradiation-doses
#3
Evagelia C Laiakis, Tytus D Mak, Steven J Strawn, Yi-Wen Wang, Bo-Hyun Moon, Pelagie Ake, Albert J Fornace
Exposures to ionizing radiation (IR) may either be accidental or intentional, for medical purposes or even through terrorist actions. As certain populations emerge to be more radiosensitive than others, it is imperative to assess those individuals and treat them accordingly. To demonstrate the feasibility of rapid identification of such cases, we utilized the highly radiosensitive mouse model Atm-/- in the C57BL/6 background, and evaluated the urinary responses in 8-10 week old male mice at early time points (4, 24, and 72 h) after exposure to their respective LD50/30 doses [4 Gy for Atm-/- , and 8 Gy for wild type (WT)]...
August 10, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/30011856/facile-preparation-of-n-glycosylated-10-piperazinyl-artemisinin-derivatives-and-evaluation-of-their-antimalarial-and-cytotoxic-activities
#4
Yuet Wu, Silvia Parapini, Ian D Williams, Paola Misiano, Ho Ning Wong, Donatella Taramelli, Nicoletta Basilico, Richard K Haynes
According to the precepts that C-10 amino-artemisinins display optimum biological activities for the artemisinin drug class, and that attachment of a sugar enhances specificity of drug delivery, polarity and solubility so as to attenuate toxicity, we assessed the effects of attaching sugars to N-4 of the dihydroartemisinin (DHA)-piperazine derivative prepared in one step from DHA and piperazine. N -Glycosylated DHA-piperazine derivatives were obtained according to the Kotchetkov reaction by heating the DHA-piperazine with the sugar in a polar solvent...
July 13, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29968540/synthesis-and-structural-elucidation-of-novel-benzothiazole-derivatives-as-anti-tubercular-agents-in-silico-screening-for-possible-target-identification
#5
Katharigatta N Venugopala, Sandeep Chandrashekharappa, Melendhran Pillay, Subhrajyoti Bhandary, Mahmoud Kandeel, Fawzi M Mahomoodally, Mohamed A Morsy, Deepak Chopra, Bandar E Aldhubiab, Mahesh Attimarad, Osama I Alwassil, Sree Harsha, Koleka Mlisana
BACKGROUND: Benzothiazole derivatives are known for anti-TB properties. Based on the known antiTB benzothiazole pharmacophore, in the present study, we described the synthesis, structural elucidation, and anti-tubercular screening of a series of novel benzothiazole (BNTZ) derivatives (BNTZ 1-7 and BNTZ 8-13). OBJECTIVE: Development of benzothiazole based anti-TB compounds. METHODS: Title compounds are synthesized by microwave method and purified by column chromatography...
July 3, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29968034/isomerases-and-epimerases-for-biotransformation-of-pentoses
#6
REVIEW
Zheng Fang, Wenli Zhang, Tao Zhang, Cuie Guang, Wanmeng Mu
Pentoses represent monosaccharides with five carbon atoms. They are organized into two main groups, aldopentoses and ketopentoses. There are eight aldopentoses and four ketopentoses and each ketopentose corresponds to two aldopentoses. Only D-xylose, D-ribose, and L-arabinose are natural sugars, but others belong to rare sugars that occur in very small quantities in nature. Recently, rare pentoses attract much attention because of their great potentials for commercial applications, especially as precursors of many important medical drugs...
July 2, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29953880/diabetex-a-novel-approach-for-diabetic-wound-healing
#7
Alshaymaa Amin Zaki El-Bahy, Yara Mohamed Aboulmagd, Mohanad Zaki
INTRODUCTION AND AIM: Wound healing is an orderly complex process involving inflammation, clotting, re-epithelialization, neovascularization and wound closure. In diabetic patients, such process is impaired and delayed, posing negative economic as well as social consequences. Diabetex, (patency# EP 0877617 A1) composed of L-alanine, d-ribose, nicotinic acid and calcium ascorbate, which was initially introduced to treat cancer is thought to have anti- diabetic effects. The present study was designed to investigate the therapeutic merit of diabetex as well as the cellular mechanisms involved in such effects and its safety profile compared to metformin in wounded diabetic rats...
June 25, 2018: Life Sciences
https://www.readbyqxmd.com/read/29944092/ruegeria-denitrificans-sp-nov-a-marine-bacterium-in-the-family-rhodobacteraceae-with-the-potential-ability-for-cyanophycin-synthesis
#8
David R Arahal, Teresa Lucena, Lidia Rodrigo-Torres, María J Pujalte
Strain CECT 5091T , an aerobic, marine, Gram-reaction- and Gram-stain-negative, chemoheterotrophic bacterium was isolated from oysters harvested off the Spanish Mediterranean coast. Analysis of the 16S rRNA gene sequence placed the strain within the genus Ruegeria, in the family Rhodobacteraceae, with 16S rRNA gene similarities of 98.7, 98.7 and 98.4 % to Ruegeria conchae, Ruegeria atlanticaand Ruegeria arenilitoris, respectively. Average nucleotide identities (ANI) and in silico DNA-DNA hybridization (DDH) were determined, comparing the genome sequence of CECT 5091T with those of the type strains of 12 species of the genus Ruegeria: the values obtained were always below the thresholds (95-96 % ANI, 70 % in silico DDH) used to define genomic species, proving that CECT 5091T represents a novel species of the genus Ruegeria...
June 26, 2018: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/29928149/pharmacokinetic-evaluation-of-d-ribose-after-oral-and-intravenous-administration-to-healthy-rabbits
#9
Karem H Alzoubi, Zuhair Bani Ismail, Mohamed K Al-Essa, Osama Y Alshogran, Reem F Abutayeh, Nareman Abu-Baker
Introduction: This study explored D-ribose pharmacokinetics after intravenous (IV) and oral administration to healthy rabbits. Materials and methods: D-ribose was administered once as 420 mg/kg (N=4) or 840 mg/kg (N=6) dose intravenously, or as an oral dose of 420 mg/kg (N=3) or 840 mg/kg (N=3). Serum was obtained at various time points, up to 210 minutes after administration. Urine was also collected after IV administration. Pharmacokinetic parameters were determined from drug concentration-time data using Kinetica software...
2018: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/29920084/exploration-of-the-relationship-between-intestinal-colostrum-or-milk-and-serum-metabolites-in-neonatal-calves-by-metabolomics-analysis
#10
Yunxia Qi, Xiaowei Zhao, Dongwei Huang, Xiaocheng Pan, Yongxin Yang, Huiling Zhao, Han Hu, Guanglong Cheng
In contrast to colostral immunoglobulins, changes in metabolite composition of ingested colostrum in the gut have received little attention. Here, we characterized the metabolite profiles of colostrum and milk, ingested colostrum and milk, and serum of neonatal calves by liquid chromatography tandem-mass spectrometry and gas chromatography-mass spectrometry metabolomics approaches. Colostrum and milk underwent similar changes in metabolite profiles in the gut after being ingested. These changes were characterized by increases in methionine, glutamate, thymine, and phosphorylcholine...
July 11, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29851474/overview-of-the-development-of-dpre1-inhibitors-for-combating-the-menace-of-tuberculosis
#11
Rupesh V Chikhale, Mahesh A Barmade, Prashant R Murumkar, Mange Ram Yadav
Decaprenylphosphoryl-β-d-ribose 2'-epimerase (DprE1), a vital enzyme for cell wall synthesis, plays a crucial role in the formation of lipoarabinomannan and arabinogalactan. It was first reported as a druggable target on the basis of inhibitors discovered in high throughput screening of a drug library. Since then, inhibitors with different types of chemical scaffolds have been reported for their activity against this enzyme. Formation of a covalent or noncovalent bond by the interacting ligand with the enzyme causes loss of its catalytic activity which ultimately leads to the death of the mycobacterium...
June 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29846073/proton-collision-on-deoxyribose-originating-from-doubly-ionized-water-molecule-dissociation
#12
Marie-Anne Hervé du Penhoat, Nely Rodrı Guez Moraga, Marie-Pierre Gaigeot, Rodolphe Vuilleumier, Ivano Tavernelli, Marie-Fraņcoise Politis
In this work, we studied the fragmentation dynamics of 2-deoxy-d-ribose (DR) in solution that arises from the double ionization of a water molecule in its primary hydration shell. This process was modeled in the framework of ab initio molecular dynamics. The charge unbalanced in the solvent molecules produces a Coulomb explosion with the consequent release of protons with kinetic energy in the few electronvolts range, which collide with the surrounding molecules in solution inducing further chemical reactions...
June 21, 2018: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29782986/antiglycation-study-of-hmg-r-inhibitors-and-tocotrienol-against-glycated-bsa-and-ldl-a-comparative-study
#13
Rabia Nabi, Sahir Sultan Alvi, Rizwan Hasan Khan, Shafeeque Ahmad, Saheem Ahmad, M Salman Khan
Non-enzymatic glycation mediated advanced glycation end products (AGEs) generation results in the pathogenesis of diabetic complications and atherosclerotic cardiovascular disease (ASCVD) which is greatly influenced by 3-hydroxy-3-methyl-glutaryl Co-A reductase (HMG-R) activity. HMG-R inhibitors, statins, are well known for reducing mortality and morbidity of ASCVD in patients with diabetes due to their pleiotropic effects independent of cholesterol lowering. Due to distinct chemical structures, various statins may play important role in the inhibition of AGEs mediated pathologies...
September 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29780691/understanding-d-ribose-and-mitochondrial-function
#14
Diane E Mahoney, John B Hiebert, Amanda Thimmesch, John T Pierce, James L Vacek, Richard L Clancy, Andrew J Sauer, Janet D Pierce
Mitochondria are important organelles referred to as cellular powerhouses for their unique properties of cellular energy production. With many pathologic conditions and aging, mitochondrial function declines, and there is a reduction in the production of adenosine triphosphate. The energy carrying molecule generated by cellular respiration and by pentose phosphate pathway, an alternative pathway of glucose metabolism. D-ribose is a naturally occurring monosaccharide found in the cells and particularly in the mitochondria is essential in energy production...
2018: Advances in bioscience and clinical medicine
https://www.readbyqxmd.com/read/29750132/potential-clinical-benefits-of-d-ribose-in-ischemic-cardiovascular-disease
#15
REVIEW
Linda M Shecterle, Kathleen R Terry, John A St Cyr
Cardiovascular disease still remains the leading cause of deaths worldwide. Atherosclerosis, the most common type of cardiovascular disease, has continued to progress due to many factors, genetics, and lifestyles. All cells require adequate adenosine triphosphate (ATP) levels to maintain their integrity and function. Myocardial ischemia commonly found in atherosclerosis can produce lower levels of ATP, which affects not only cellular energy, but also alters normal function. D-ribose, a naturally occurring pentose carbohydrate, has been shown to increase cellular energy levels and improve function following ischemia in pre-clinical studies and have demonstrated potential benefits in clinical evaluations...
March 9, 2018: Curēus
https://www.readbyqxmd.com/read/29713062/thymidine-catabolism-promotes-nadph-oxidase-derived-reactive-oxygen-species-ros-signalling-in-kb-and-yumoto-cells
#16
Sho Tabata, Masatatsu Yamamoto, Hisatsugu Goto, Akiyoshi Hirayama, Maki Ohishi, Takuya Kuramoto, Atsushi Mitsuhashi, Ryuji Ikeda, Misako Haraguchi, Kohichi Kawahara, Yoshinari Shinsato, Kentaro Minami, Atsuro Saijo, Yuko Toyoda, Masaki Hanibuchi, Yasuhiko Nishioka, Saburo Sone, Hiroyasu Esumi, Masaru Tomita, Tomoyoshi Soga, Tatsuhiko Furukawa, Shin-Ichi Akiyama
Thymidine phosphorylase (TP) is a rate-limiting enzyme in the thymidine catabolic pathway. TP is identical to platelet-derived endothelial cell growth factor and contributes to tumour angiogenesis. TP induces the generation of reactive oxygen species (ROS) and enhances the expression of oxidative stress-responsive genes, such as interleukin (IL)-8. However, the mechanism underlying ROS induction by TP remains unclear. In the present study, we demonstrated that TP promotes NADPH oxidase-derived ROS signalling in cancer cells...
April 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29686156/metabolism-of-sklb-tb1001-a-potent-antituberculosis-agent-in-animals
#17
Lu Xiong, Chao Gao, Yao-Jie Shi, Xin Tao, Cui-Ting Peng, Juan Rong, Kun-Lin Liu, Qian Lei, Yi-Wen Zhang, Ning-Yu Wang, Luo-Ting Yu
Tuberculosis is a major global health problem, and the emergence of multidrug-resistant and extensively drug-resistant strains has increased the difficulty of treating this disease. Among the novel antituberculosis drugs in the pipeline, decaprenylphosphoryl-beta-d-ribose-2-epimerase (DprE1) inhibitors such as BTZ043 and pBTZ169 exhibited extraordinary antituberculosis potency. Here, the metabolites of the new DprE1 inhibitor SKLB-TB1001 in vivo and its inhibition of cytochrome P450 isoforms and plasma protein binding (PPB) in vitro were studied...
July 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29610214/two-component-flavin-dependent-riboflavin-monooxygenase-degrades-riboflavin-in-devosia-riboflavina
#18
Hiroshi Kanazawa, Ryosuke Shigemoto, Yukie Kawasaki, Ken-Ichi Oinuma, Akira Nakamura, Shunsuke Masuo, Naoki Takaya
The actinobacterium Microbacterium maritypicum splits riboflavin (vitamin B2 ) into lumichrome and d-ribose. However, such degradation by other bacteria and the involvement of a two-component flavin-dependent monooxygenase (FMO) in the reaction remain unknown. Here we investigated the mechanism of riboflavin degradation by the riboflavin-assimilating alphaproteobacterium Devosia riboflavina (formerly Pseudomonas riboflavina ). We found that adding riboflavin to bacterial cultures induced riboflavin-degrading activity and a protein of the FMO family that had 67% amino acid identity with the predicted riboflavin hydrolase (RcaE) of M...
June 15, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29606104/study-protocol-randomized-controlled-trial-reducing-symptom-burden-in-patients-with-heart-failure-with-preserved-ejection-fraction-using-ubiquinol-and-or-d-ribose
#19
Janet D Pierce, Diane E Mahoney, John B Hiebert, Amanda R Thimmesch, Francisco J Diaz, Carol Smith, Qiuhua Shen, Dinesh Pal Mudaranthakam, Richard L Clancy
BACKGROUND: Heart failure (HF), the leading cause of morbidity and mortality in the US, affects 6.6 million adults with an estimated additional 3 million people by 2030. More than 50% of HF patients have heart failure with preserved left ventricular ejection fraction (HFpEF). These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. Patients with HFpEF experience symptoms of: (1) fatigue; (2) shortness of breath; and (3) swelling (edema) of the lower extremities...
April 2, 2018: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/29577866/synthesis-and-anticancer-properties-of-novel-truncated-carbocyclic-nucleoside-analogues
#20
Balija Sivakrishna, Sehbanul Islam, Amarendra Panda, Maddi Saranya, Manas Kumar Santra, Shantanu Pal
Series of novel truncated carbocyclic nucleoside analogues have been synthesized from the versatile starting material D-ribose and their anticancer activities have been evaluated. The nucleoside analogues induced cytotoxicity in breast and ovarian cancer cell lines. These compounds are less cytotoxic to normal kidney cell line (HEK 293) as compared to the cancer cells. Among the synthesized compounds, 1b and 1d showed the better cytotoxic effect with IC50 44 and 54 μM, in MCF7 cells, respectively. These compounds inactivate the important signaling kinases AKT and mTOR and thereby induce autophagy...
March 22, 2018: Anti-cancer Agents in Medicinal Chemistry
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