- Characterization and cytotoxicity evaluation of biocompatible amino acid esters used to convert salicylic acid into ionic liquids
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The technological utility of active pharmaceutical ingredients (APIs) is greatly enhanced when they are transformed into ionic liquids (ILs). API-ILs have better solubility, thermal stability, and the efficacy in topical delivery than solid or crystalline drugs. However, toxicological issue of API-ILs is the main challenge for their application in drug delivery. To address this issue, 11 amino acid esters (AAEs) were synthesized and investigated as biocompatible counter cations for the poorly water-soluble drug salicylic acid (Sal) to form Sal-ILs. The AAEs were characterized using 1H and 13C NMR, FTIR, elemental, and thermogravimetric analyses. The cytotoxicities of the AAE cations, Sal-ILs, and free Sal were investigated using mammalian cell lines (L929 and HeLa). The toxicities of the AAE cations greatly increased with inclusion of long alkyl chains, sulfur, and aromatic rings in the side groups of the cations. Ethyl esters of alanine, aspartic acid, and proline were selected as a low cytotoxic AAE. The cytotoxicities of the Sal-ILs drastically increased compared with the AAEs on incorporation of Sal into the cations, and were comparable to that of free Sal. Interestingly, the water miscibilities of the Sal-ILs were higher than that of free Sal, and the Sal-ILs were miscible with water at any ratio. A skin permeation study showed that the Sal-ILs penetrated through skin faster than the Sal sodium salt. These results suggest that AAEs could be used in biomedical applications to eliminate the use of traditional toxic solvents for transdermal delivery of poorly water-soluble drugs.
- Moshikur, Rahman Md.,Chowdhury, Md. Raihan,Wakabayashi, Rie,Tahara, Yoshiro,Moniruzzaman, Muhammad,Goto, Masahiro
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- Optical activity 1,5-substituted-1,3,5-hexahydrotriazine-2-N-nitroimines: Synthesis and insecticidal activity
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Twelve novel neonicotinoid analogues 1-(2-furfuryl)-5-substituted-1,3,5- hexahydrotriazine-2-N-nitroimines 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3l were synthesized. Their structures were characterized by 1H NMR, IR, and elemental analysis. The preliminary bioassay tests showed that all the title compounds gave ≥90% mortality against Nilaparvata lugen 500 mg/L.
- Xue, Si-Jia,Bu, Hong-Fei,Liu, Li,Xu, Xiao,Ma, Xubo,Zhu, Jun
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p. 1067 - 1070
(2013/10/21)
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- Chiral 1,5-disubstituted 1,3,5-hexahydrotriazine-2-N-nitroimine analogues as novel potent neonicotinoids: Synthesis, insecticidal evaluation and molecular docking studies
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A new series of 1,5-disubstituted 1,3,5-hexahydrotriazine-2-N-nitroimines (4a-4x) were designed and synthesized as novel chiral neonicotinoid analogues. The single-crystal structure of 4n was further determined by X-ray diffraction, and its S configuration was confirmed. Preliminary bioassay showed that compound 4e, 4k, 4u, 4v exhibited excellent insecticidal activities at 100 mg/L, while 4k had >90% mortality at 10 mg/L, which suggested it could be used as a lead for future development. Modeling the inhibitor-nAChR complexes by molecular docking studies explained the structure-activity relationships observed in vitro, and revealed an intriguing molecular binding mode at the active site of nAChR, which raised the possibility that these analogues may arbitrate their insecticidal activity through a mechanism other than imidacloprid.
- Sun, Chuanwen,Zhu, Jun,Wang, Haifeng,Jin, Jia,Xing, Jiahua,Yang, Dingrong
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experimental part
p. 11 - 20
(2011/02/27)
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- Sulfur-containing β-amino alcohols as catalysts in enantioselective synthesis
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Oxazaborolidine catalysts generated in situ from cyclic or acyclic sulfur containing (R)-cysteine, (S)-penicillamine and (S)-methionine derivates and BH3 have been applied successfully to the enantiocontrolled, catalytic reduction of aromatic ketones. The corresponding sec alcohols could be obtained in excellent enantiomeric excess, up to 100% ee. Using these chiral auxiliaries in the enantioselective addition of diethylzinc to aldehydes afforded optically active sec alcohols in enantiomeric excess up to 93% ee.
- Trentmann, Wilhelm,Mehler, Thomas,Martens, Juergen
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p. 2033 - 2043
(2007/10/03)
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- 9. Les β-cetonitriles groupes protecteurs de la fonction amine. Preparation d'amino-alcools
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β-Ketonitrile-Derived Protecting Groups of the Amino Function.Synthesis of Amino Alcohols.The amino group of natural L-amino acid esters is protected by condensation with 2-oxocyclopentanenitrile (1) or 2-formyl-2-phenylacetonitrile (10).Only the ester group of the formed cyanoenamino esters 2 and 11 reacts with nucleophilic reagents such as organometallics (RMgX, RLi), borohydrides, or metal amides, whereas the cyanoenamino group is unchanged (Schemes 1 and 2).Cyanoenamino alcohols obtained by reduction of cyanoenamino esters 2 are hydrolyzed under acidic conditions to amino alcohols with retention of the configuration of the starting amino acid.This sequence of reactions allows to prepare derivatives of L-tyrosinol from (-)-L-tyrosine (see, e.g., Scheme 4).Cyanoenamino esters 11 are readily methylated at the N-atom to give N-methylated cyanoenamino esters (Scheme 3).This property is exploited on the way of multistep procedure to obtain N-methylated amino alcohols homologous to natural (-)-(1R,2S)-ephedrine.
- Abarbri, Mohamed,Guignard, Alain,Lamant, Maurice
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p. 109 - 121
(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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