- Prebiotic Origin of Pre-RNA Building Blocks in a Urea “Warm Little Pond” Scenario
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Urea appears to be a key intermediate of important prebiotic synthetic pathways. Concentrated pools of urea likely existed on the surface of the early Earth, as urea is synthesized in significant quantities from hydrogen cyanide or cyanamide (widely accepted prebiotic molecules), it has extremely high water solubility, and it can concentrate to form eutectics from aqueous solutions. We propose a model for the origin of a variety of canonical and non-canonical nucleobases, including some known to form supramolecular assemblies that contain Watson-Crick-like base pairs.The dual nucleophilic-electrophilic character of urea makes it an ideal precursor for the formation of nitrogenous heterocycles. We propose a model for the origin of a variety of canonical and noncanonical nucleobases, including some known to form supramolecular assemblies that contain Watson-Crick-like base pairs. These reactions involve urea condensation with other prebiotic molecules (e. g., malonic acid) that could be driven by environmental cycles (e. g., freezing/thawing, drying/wetting). The resulting heterocycle assemblies are compatible with the formation of nucleosides and, possibly, the chemical evolution of molecular precursors to RNA. We show that urea eutectics at moderate temperature represent a robust prebiotic source of nitrogenous heterocycles. The simplicity of these pathways, and their independence from specific or rare geological events, support the idea of urea being of fundamental importance to the prebiotic chemistry that gave rise to life on Earth.
- Menor Salván,Bouza, Marcos,Fialho, David M.,Burcar, Bradley T.,Fernández, Facundo M.,Hud, Nicholas V.
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- Design, synthesis and biological evaluation of pyrimidine-based derivatives as antitumor agents
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In this paper we made a contentious effort to afford heterocyclic compounds with interesting biological activities. The reaction of guanidine with either activated methylene groups, arylhydrazono derivatives, dicyanopropene derivatives, malononitrile dimer or arylhydarazononitrile derivatives afforded diaminopyrimidine derivatives, aryldiazenyl pyrimidine derivatives, fused pyridopyrimidne derivatives and pyrimidopyridazine derivatives respectively. Also the reaction of guanidine with phenylhydrazono carbonyl compounds produced phenyldiazenyl pyrimidine derivatives. The latter products were directed toward the reaction with either acetic anhydride or ethylcyanoacetate to form acetamidopyrimidine derivatives and cyanoacetamidopyrimidine derivatives respectively. The latter products underwent cyclization via reaction with either activated methylene groups or activated methylene carbonyl compounds afforded pyridopyrimidne derivatives. 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.
- AlHazmi, Hassan A.,Albratty, Mohammed M.,El-Sharkawy, Karam A.
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p. 227 - 238
(2020/10/06)
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- Efficient self-assembly in water of long noncovalent polymers by nucleobase analogues
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Molecular self-assembly is widely appreciated to result from a delicate balance between several noncovalent interactions and solvation effects. However, current design approaches for achieving self-assembly in water with small, synthetic molecules do not consider all aspects of the hydrophobic effect, in particular the requirement of surface areas greater than 1 nm2 for an appreciable free energy of hydration. With the concept of a minimum hydrophobic surface area in mind, we designed a system that achieves highly cooperative self-assembly in water. Two weakly interacting low-molecular-weight monomers (cyanuric acid and a modified triaminopyrimidine) are shown to form extremely long supramolecular polymer assemblies that retain water solubility. The complete absence of intermediate assemblies means that the observed equilibrium is between free monomers and supramolecular assemblies. These observations are in excellent agreement with literature values for the free energy of nucleic acid base interactions as well as the calculated free energy penalty for the exposure of hydrophobic structures in water. The results of our study have implications for the design of new self-assembling structures and hydrogel-forming molecules and may provide insights into the origin of the first RNA-like polymers.
- Cafferty, Brian J.,Gállego, Isaac,Chen, Michael C.,Farley, Katherine I.,Eritja, Ramon,Hud, Nicholas V.
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supporting information
p. 2447 - 2450
(2013/03/28)
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- Microwave-expedited one-pot, two-component, solvent-free synthesis of functionalized pyrimidines
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The synthesis of a series of diversely substituted pyrimidines under solvent-free conditions in good yields is described. Under microwave irradiation, a variety of nucleophilic substrates containing the N?C?N unit with ?-dicarbonyl compounds, ethyl cyanoacetate, malononitrile, and chalcones was cyclized to give pyrimidines. A combinatorial type approach for a one-step synthesis has been developed where a ring-closing condensation is followed by spontaneous aromatization to afford 28 functionalized and aryl/alkyl substituted pyrimidines. CSIRO 2007.
- Goswami, Shyamaprosad,Jana, Subrata,Dey, Swapan,Kumar Adak, Avijit
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p. 120 - 123
(2008/02/11)
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- Design, synthesis and evaluation of 5-substituted amino-2,4-diamino-8- chloropyrimido-[4,5-b]quinolines as novel antimalarials
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The design, synthesis and evaluation of 5-substituted amino-2,4-diamino-8- chloropyrimido-[4,5-b]quinolines as potent antimalarials is reported. Novel 5-substituted amino-2,4-diamino-8-chloropyrimido-[4,5-b]quinolines were designed based on a pharmacophore developed for potent antimalarial activity using Chem-X and MOE softwares. The designed molecules were synthesized by following a novel route and were evaluated by Rane's test for blood schizonticidal activity in mice infected by Plasmodium berghei. Based on the Mean Survival Time (MST) data, of the nine compounds evaluated, three had curative potential when compared with chloroquine.
- Joshi, Advait A.,Narkhede, Sachin S.,Viswanathan
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- 3-deoxyglucosone and skin
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The invention relates to a method of removing 3-deoxyglucosone and other alpha-dicarbonyl sugars from skin. The invention further relates to methods of inhibiting production and function of 3-deoxyglucosone and other alpha-dicarbonyl sugars in skin. The invention also relates to methods of treating 3-deoxyglucosone and other alpha-dicarbonyl sugars associated diseases and disorders of skin.
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- Amino-substituted pyrimidines, derivatives and methods of use therefor
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The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises an agent capable of inhibiting the formation of advanced glycosylation end products of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
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- Decarbonylation of Some Pyrimidine-5-carboxaldehydes
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In the course of determining the ultraviolet spectra of some 2,4,6-trisubstituted-pyrimidine-5-carboxaldehydes we discovered the facile loss of the formyl group.The reaction appears to be restricted to pyrimidine-5-carboxaldehydes containing three strongly electron donating substituents.Loss of the formyl group occurs at room temperature only in methanol with large excess of acid.Other alcohols and water fail to afford the decarbonylated product.A suggested pathway for this reaction is offered.
- Delia, Thomas J.,Polenz, Barry,Martin, Mary C.
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p. 1697 - 1700
(2007/10/02)
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