- Exploring the ability of dihydropyrimidine-5-carboxamide and 5-benzyl-2,4-diaminopyrimidine-based analogues for the selective inhibition of L. major dihydrofolate reductase
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To tackle leishmaniasis, search for efficient therapeutic drug targets should be pursued. Dihydrofolate reductase (DHFR) is considered as a key target for the treatment of leishmaniasis. In current study, we are interested in the design and synthesis of selective antifolates targeting DHFR from L. major. We focused on the development of new antifolates based on 3,4-dihydropyrimidine-2-one and 5-(3,5-dimethoxybenzyl)pyrimidine-2,4-diamine motif. Structure activity relationship (SAR) studies were performed on 4-phenyl ring of dihydropyrimidine (26–30) template. While for 5-(3,5-dimethoxybenzyl)pyrimidine-2,4-diamine, the impact of different amino acids (valine, tryptophan, phenylalanine, and glutamic acid) and two carbon linkers were explored (52–59). The synthesized compounds were assayed against LmDHFR. Compound 59 with the IC50 value of 0.10 μM appeared as potent inhibitors of L. major. Selectivity for parasite DHFR over human DHFR was also determined. Derivatives 55–59 demonstrated excellent selectivity for LmDHFR. Highest selectivity for LmDHFR was shown by compounds 56 (SI = 84.5) and 58 (SI = 87.5). Compounds Antileishmanial activity against L. major and L. donovani promastigotes was also performed. To explore the interaction pattern of the synthesized compounds with biological macromolecules, the docking studies were carried out against homology modelled LmDHFR and hDHFR targets.
- Bibi, Maria,Qureshi, Naveeda Akhter,Sadiq, Abdul,Farooq, Umar,Hassan, Abbas,Shaheen, Nargis,Asghar, Irfa,Umer, Duaa,Ullah, Azmat,Khan, Farhan A.,Salman, Muhammad,Bibi, Ahtaram,Rashid, Umer
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- Cooperative Pd/Cu Catalysis: Multicomponent Synthesis of Tetrasubstituted Imidazolones from Methyl α-Isocyanoacetates, Primary Amines, and Aryl(vinyl) Iodides
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Three-component reaction of methyl α,α-disubstituted α-isocyanoacetates, primary amines, and aryl(vinyl) halides in the presence of Pd(OAc)2 (0.05 equiv) and Cu2O (1.0 equiv) provided 2,3,5,5-tetrasubstituted imidazolones via the for
- Clemenceau, Antonin,Wang, Qian,Zhu, Jieping
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supporting information
p. 126 - 129
(2018/01/17)
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- Synthesis and biological evaluation of novel lipoamino acid derivatives
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Seven novel lipoamino acid conjugates were synthesized from methyl oleate and amino acids. Methyl oleate was grafted to different amino acids using thioglycolic acid as a spacer group. Seven derivatives (3a-g) were prepared and characterized by spectral data (NMR, IR and MS spectral studies). All the derivatives were studied for their antimicrobial, anti-biofilm and anticancer activities. Among all the derivatives, it was found that compound 3b was the most potent antibacterial compound which showed good activity against four Gram positive bacterial strains and also exhibited excellent antifungal activity against a fungal strain. In the anti-biofilm assay, compound 3b showed promising activity with IC50 value of 2.8 μM against Bacillus subtilis MTCC 121. All the compounds showed anticancer activities with 3c showing promising anticancer activity (IC50 = 15.3-22.4 μM) against the four cell lines tested.
- Kaki, Shiva Shanker,Arukali, Sammaiah,Korlipara, Padmaja V.,Prasad,Yedla, Poornachandra,Ganesh Kumar
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supporting information
p. 209 - 212
(2015/12/20)
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- A small molecule peptidomimetic of spider silk and webs
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A peptidomimetic compound containing leucine, tyrosine and malonic acid self-assembles through various noncovalent interactions to form spider silk-like fibers at ambient temperature. From the high-density liquid, a liquid-solid phase transition is initiated at 20 °C and solidification occurs upon contact with air. The fiber has comprehensive mechanical strength and optical properties similar to spider silk, and can be used to mimic a natural spider web. This journal is
- Maji, Krishnendu,Sarkar, Rajib,Bera, Santu,Haldar, Debasish
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supporting information
p. 12749 - 12752
(2015/05/20)
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- FATTY ACID ACETYLATED SALICYLATES AND THEIR USES
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The invention relates to Fatty Acid Acetylated Salicylate Derivatives; compositions comprising an effective amount of a Fatty Acid Acetylated Salicylate Derivative; and methods for treating or preventing an inflammatory disorder comprising the administration of an effective amount of a Fatty Acid Acetylated Salicylate Derivative.
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Page/Page column 118
(2010/03/04)
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- Enantiomeric resolution of α-amino acid derivatives on two diastereomeric chiral stationary phases based on chiral crown ethers incorporating two different chiral units
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Two diastereomeric chiral stationary phases (CSPs) were applied to the liquid chromatographic resolution of various racemic a-amino methyl esters, α-amino N,N-diethylamides and α-amino N-propylamides. The CSP incorporating (R)-3,3' -diphenyl-1,1' -binaphtyl and (R,R)-tartaric acid unit as chiral barriers did not show any chiral recognition. In contrast, the CSP incorporating (R)-3,3'-diphenyl-1,1'-binaphtyl and (S,S)-tartaric acid unit as chiral barriers was found to show excellent chiral recognition especially for the two enantiomers of a-amino N-propylamides. Some of a-amino methyl esters and α-amino N,N-diethylamides were also resolved on the CSP incorporating (R)-3,3'-diphenyl-1,1'-binaphtyl and (S,S)-tartaric acid unit. From these results it was concluded that the two chiral units composing the diastereomeric CSPs can show "matched" or "mismatched" effect on the chiral recognition according to their absolute stereochemistry.
- Kim, Hee Jin,Choi, Hee Jung,Cho, Yoon Jae,Hyun, Myung Ho
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body text
p. 1551 - 1554
(2010/10/20)
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- Design and synthesis of N-methylmaleimide indolocarbazole bearing modified 2-acetamino acid moieties as Topoisomerase I inhibitors
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A novel series of N-methylmaleimide indolocarbazole derivatives bearing modified 2-acetamino acid moieties are first reported. The cytotoxic effects of these compounds were tested in five human tumor cell lines. The potent compounds 9a, 9b, 9d, and 9e have been further evaluated for their effect on Topoisomerase I (TOPO I) and cancer cell cycle. It is concluded that the indolocarbazoles with alkyl piperazine or morpholine substituent groups instead of esters or glycosyl residues would have better activities against tumors.
- Li, Zhiyu,Zhai, Fuming,Zhao, Li,Guo, Qinglong,You, Qidong
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scheme or table
p. 406 - 409
(2011/02/26)
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- A resource-efficient and highly flexible procedure for a three-component synthesis of 2-imidazolines
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(Chemical Equation Presented) A multicomponent reaction between α-acidic isonitriles, primary amines, and carbonyl compounds was studied using 14 different solvents. Depending on the isocyanide that was used, optimal yields for the three-component synthesis of 2H-2-imidazolines were observed in different solvents. The solvents could be used as purchased, and in situ preformation of the imine was not required. By selecting the appropriate solvent, it was possible to considerably expand the range of compatible isocyanides toward less α-acidic isocyanides. Further process simplification was achieved by performing the reaction at higher concentrations and avoiding purification by column chromatography, resulting in a fast, easy to perform, and resource-efficient protocol for this three-component reaction.
- Elders, Niels,Schmitz, Rob F.,De Kanter, Frans J. J.,Ruijter, Eelco,Groen, Marinus B.,Orru, Romano V. A.
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p. 6135 - 6142
(2008/02/10)
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- Electrophilic amination of racemic and non-racemic allenyltitaniums. One-pot synthesis of α-hydrazinoalkynes from propargylic alcohol derivatives
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Successive treatment of propargylic carbonates or phosphates with a Ti(O-i-Pr)4/2i-PrMgCl reagent and dialkyl azodicarboxylates gave α- hydrazinoalkynes in good yields. The reaction, which proceeded with up to 86% chiral transfer, thus has opened up a new route to optically active α- hydrazinoalkynes from the optically active propargylic compounds.
- An, Duk Keun,Hirakawa, Koichiro,Okamoto, Sentaro,Sato, Fumie
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p. 3737 - 3740
(2007/10/03)
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- ENANTIOSELECTIVE ELECTROPHILIC BOND CONSTRUCTION TO THE α-CARBON OF α-AMINOACIDS
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In this report, we describe three possibilities for aminoacid synthesis using an enantioselective electrophilic process.Thus, enantioselective carboxylation, alkylation and protonation of Schiff bases yield optically active aminoacids with e.e. up to 76percent.
- Duhamel, Lucette,Duhamel, Pierre,Fouquay, Stephane,Eddine, Jamal Jamal,Peschard, Olivier,et al.
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p. 5495 - 5506
(2007/10/02)
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- A Facile Synthesis of α-Amino Esters via Reduction of α-Nitro Esters Using Ammonium Formate as a Catalytic Hydrogen Transfer Agent
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Various nitroesters 3 were selectively and rapidly reduced to their corresponding amino esters 4 in very good yield using anhydrous ammonium formate as a catalytic hydrogen transfer agent.
- Ram, Siya,Ehrenkaufer, Richard E.
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p. 133 - 135
(2007/10/02)
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- OPTICALLY ACTIVE F-2-ISOPROPOXYPROPIONIC ACID: A NOVEL DERIVATIZING AGENT FOR GAS CHROMATOGRAPHIC ANALYSIS
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F-2-Isopropoxypropionic acid (PIPA) was resolved into enantiomers via its diastereomeric (+)-1-phenylethylamide. (+)-F-2-Isopropoxypropionyl derivatives of several chiral 1-arylalkylamines and α-amino acids were effectively resolved by gas chromatography at low temperature.
- Kawa, Hajimu,Yamaguchi, Fumihiko,Ishikawa, Nobuo
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p. 745 - 748
(2007/10/02)
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