- Investigation of permeation of theophylline through skin using selected piperazine-2,5-diones
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Transdermal administration of drugs that penetrate, in this case directly into the blood circulation, has many advantages and is promising for many drugs thanks to its easy application and good patient compliance. (S)-8-Methyl-6,9-diazaspiro[4.5]decan-7,10-dione (alaptide), has been studied as a potential chemical permeation enhancer. Based on its structure, four selected piperazine-2,5-diones were synthesized by means of multi-step synthetic pathways. All the compounds were investigated on their ability to enhance the permeation of the model drug theophylline from the hydrophilic medium propylene glycol:water (1:1). In vitro experiments were performed using vertical Franz diffusion cells at constant temperature 34 ± 0.5 ?C and using full-thickness pig (Sus scrofa f. domestica) ear skin. Withdrawn samples were analyzed by RP-HPLC for determination of the permeated amount of theophylline. All the compounds were applied in ratio 1:10 (w/w) relative to the amount of theophylline. One hour after application, the permeated amount of theophylline from formulations with alaptide and (3S,6S)-3,6-dimethylpiperazine-2,5-dione, was ca. 15- and 12-fold higher, respectively, than from the formulation without the tested compounds. Despite the enhancement ratio of both enhancers in a steady state was ca. 2.3, the pseudo-enhancement ratio in the time range from 1 to 3 h was 4.4. These enhancement ratios indicate that the compounds are able to enhance the permeation of agents through the skin; however, the short-term application of both compound formulations seems to be more advantageous. In addition, the screening of the cytotoxicity of all the prepared compounds was performed using three cell lines, and the compounds did not show any significant toxic effect.
- Pokorna, Aneta,Bobal, Pavel,Oravec, Michal,Rarova, Lucie,Bobalova, Janette,Jampilek, Josef
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- Engineered Substrate for Cyclooxygenase-2: A Pentapeptide Isoconformational to Arachidonic Acid for Managing Inflammation
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Beyond the conventional mode of working of anti-inflammatory agents through enzyme inhibition, herein, COX-2 was provided with an alternate substrate. A proline-centered pentapeptide isoconformational to arachidonic acid, which exhibited appreciable selectivity for COX-2, overcoming acetic acid- and formalin-induced pain in rats to almost 80%, was treated as a substrate by the enzyme. Remarkably, COX-2 metabolized the pentapeptide into small fragments consisting mainly of di- and tripeptides that ensured the safe breakdown of the peptide under in vivo conditions. The kinetic parameter Kcat/Km for COX-2-mediated metabolism of the peptide (6.3 × 105 M-1 s-1) was quite similar to 9.5 × 105 M-1 s-1 for arachidonic acid. Evidenced by the molecular dynamic studies and the use of Y385F COX-2, it was observed that the breakage of the pentapeptide has probably been taken place through H-bond activation of the peptide bond by the side chains of Y385 and S530.
- Kaur, Baljit,Kaur, Manpreet,Kaur, Navjot,Garg, Saweta,Bhatti, Rajbir,Singh, Palwinder
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p. 6363 - 6376
(2019/07/08)
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- 1,3-Oxazolidin-5-ones derived from proline as chiral components in the synthesis of predictive enantioselective coupling reagents
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1,3-Oxazolidin-5-ones derived from both enantiomers of proline and trichloroacetaldehyde were prepared and applied as an amine component in the synthesis of chiral predictive triazine-based coupling reagents. The reagents were found to be useful in condensations yielding enantiomerically enriched products from racemic substrates.
- KAsperowicz-Frankowska, Katarzyna,Kolesińska, Beata,Gzik, Anna,Jastrzabek, Konrad,Kamiński, Zbigniew J.
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p. 921 - 927
(2018/09/22)
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- Synthesis of chiral triazine coupling reagents based on esters of n-alkylproline and their application in the enantioselective incorporation of d or l amino acid residue directly from racemic substrate
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Esters of N-methylproline and N-allylproline were prepared and used as component for synthesis of chiral triazine based coupling reagents. N-Triazinylammonium tetrafluoroborate obtained from methylester of L-N-methylproline, 2-chloro-4,6-dimethozxy-1,3,5-
- Kasperowicz-Frankowska, Katarzyna,Gzik, Anna,Dziemidkiewicz, Michal,Kolesi-Ska, Beata,Kamiski, Zbigniew J.
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p. 994 - 1003
(2015/02/02)
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- Synthesis and bioactivity of diketopiperazine PJ147 and its derivatives from Gliocladium sp. YUP08
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Concise total synthesis of diketopiperazine PJ147, obtained from mycelium of Gliocladium sp. YUP08, has been achieved in seven steps with 43.5% overall yield. Biological evaluation of PJ147 exhibited strong inhibiting activity against A375-S2, Hela, P388, A-549, HL-60, and BEL-7420 cell lines. Thus, eight derivatives of PJ147 with high water solubility were also synthesized to facilitate the in vivo bioassay of this kind of diketopiperazines. 2014
- Li, Xue-Zheng,Chen, Gang,Wang, Hai-Feng,Hua, Hui-Ming,Pei, Yue-Hu
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p. 764 - 769
(2014/08/18)
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- Intermolecular Aminolyses of 1-Thioglycosyl Esters of N-Acylamino Acids
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Fully acetylated 1-thioglycopyranosyl esters of N-acylamino acids (1-3), comprising different 1-thio sugars, undergo aminolysis with glycine methyl ester in dichloromethane at 40° to form the corresponding N-acyldipeptide methyl esters. The relative reactivity of the C-1 thioester bond towards aminolysis depends inter alia on the structure of the sugar moiety. Acylating efficiency of the 1-thioesters was additionally demonstrated by aminolysis of 2,3,4,6-tetra-O-acetyl-1-S-(N-tert-butyloxycarbonyl-L-tyrosyl)-1-thio-β-D- glucopyranose (3h) with peptidoglycan monomer (PGM, a disaccharide-pentapeptide) in N,N-dimethylformamide at room temperature to give the corresponding disaccharide-hexapeptide.
- Ljevakovic, Durdica,Tomic, Srdanka,Tomasic, Jelka,Horvat, Jaroslav
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p. 1329 - 1337
(2007/10/03)
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- N-tert-Butylglyoxylicamide, the New Reagent for Peptide Segment Coupling by Four-Component Reaction
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In contrast to the use of other aldehyd components, the Tetra Component Reactions (4CR) of carboxyl acids and primary amines with combinations of N-tert-butylglyoxylicamide and isocyanides produce carbonamides that yield the desired stereochemically unifo
- Koenig, Stephan,Kloesel, Roland,Karl, Rosi,Ugi, Ivar
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p. 1586 - 1596
(2007/10/02)
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- SYNTHESIS OF FRAGMENTS OF THE VP1 PROTEIN OF TYPE A22 FOOT-AND-MOUTH DISEASE VIRUS. SYNTHESIS OF FRAGMENTS 134-139, 134-145, 140-145, 150-155, AND 150-159
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Fragments of peptides of the amino acid sequences (134-145) and (150-159) of the VP1 protein of the type A22 foot-and-mouth disease (FMD)virus have been synthesized by the classical methods of peptide chemistry.Oligopeptides were obt
- Khalikov, Sh. Kh.,Alieva, S. V.,Ashurov, S. G.
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p. 202 - 212
(2007/10/02)
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- KINETICS OF THE ALKALINE HYDROLYSIS OF SEVERAL N-BENZYLOXYCARBONYLDIPEPTIDE METHYL AND ETHYL ESTERS
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The reaction rates of the alkaline hydrolysis of synthesized N-protected dipeptide methyl and ethyl esters were studied systematically.From the kinetic data the energies of activation, the pre-exponential factors and the reference values at 40 deg C were calculated.The rate of hydrolysis shows to be strongly dependent on the C-terminal amino acid in the sequence Gly >> Ala/Met/Phe > Leu >> Val/Pro.Surprisingly the N-terminal amino acid also exerts an effect, but in a different sequence.N-Terminal Phe in particular shows a relative accelerating effect.Remarkable is the significantly faster ester hydrolysis of glycine containing dipeptide ethyl esters in ethanol/water compared to the corresponding methyl esters in methanol/water.
- Hoogwater, D. A.,Peereboom, M.
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p. 5325 - 5332
(2007/10/02)
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- AMINO ACIDS AND PEPTIDES. VIII. A WATER - SOLUBLE ACTIVE ESTER, PHENOLSULFONIC ACID DERIVATIVE
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N-protected amino acid 4-phenolsulfonic acid derivative esters, such as 2,6-dibromo-4-sulfophenyl ester sodium salt, 2,6-dichloro-4-sulfophenyl ester potassium salt and 2-nitro-4-sulfophenyl ester sodium salt, were prepared.These esters are water - soluble active esters, and were applied for rhe synthesys of Leu-enkephalin.Keywords - water - soluble active ester; 2,6-dichloro-4-sulfophenyl ester; 2,6-dibromo-4-sulfophenyl ester; 2-nitro-4-sulfophenyl ester; peptide synthesis; Leu-enkephalin
- Kawasaki, Koichi,Tsuji, Toshiki,Maeda, Misuko,Matsumoto, Tatsuya,Hirase, Katsuhiko
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p. 1044 - 1048
(2007/10/02)
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- PEPTIDE BOND FORMATION BY INTERMOLECULAR AMINOLYSIS OF D-GLUCOPYRANOSYL ESTERS OF AMINO ACIDS
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The reaction of HO-protected and -unprotected D-glucopyranosyl esters of N-acylamino acids (Gly, Ala, Phe) with glycine and phenylalanine methyl esters in N,N-dimethylformamide at 38 deg C and dichloromethane at 40 deg C, respectively, led to repture of the C-1 ester bond and formation of the corresponding N-acyldipeptide methyl ester.The relative reactivity of the C-1 ester bond toward aminolysis was greatly influenced by the structure of the amino acid nucleophile, the nature of the aglycon side-chain group, and the anomeric configuration of the D-glucopyranosyl ester involved.Evidence for a substantially lower acylating efficiency of the ester at C-2, as compared to that at C-1, was obtained by aminolysis of two fully acetylated 2-O-(acylaminoacyl)-β-D-glucopyranoses.Treatment of 1-O-(glycylglycylglycyl)-β-D-glucopyranose with phenylalanine methyl ester in N,N-dimethylformamide led to parallel hydrolysis and intermolecular aminolysis, to give the tripeptide and tetrapeptide methyl ester.
- Horvat, Stefica,Keglevic, Dina
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