Molecules

117 KiB

Open AccessArticle

The Drug Release Profile from Calcium-induced Alginate Gel Beads Coated with an Alginate Hydrolysate

by Yoshifumi Murata, Daisaku Jinno, Dongchun Liu, Takshi Isobe, Kyouko Kofuji and Susumu Kawashima

Molecules 2007, 12(11), 2559-2566; https://doi.org/10.3390/12112559 - 29 Nov 2007

Cited by 41 | Viewed by 13785

Abstract

Calcium-induced alginate gel bead (Alg-Ca) coated with an alginate hydrolysate(Alg), e.g. the guluronic acid block (GB) was prepared and the model drug, hydrocortisonerelease profiles were investigated under simulated gastrointestinal conditions. Theirmolecular weights were one sixth or one tenth that of Alg and the [...] Read more.

Calcium-induced alginate gel bead (Alg-Ca) coated with an alginate hydrolysate(Alg), e.g. the guluronic acid block (GB) was prepared and the model drug, hydrocortisonerelease profiles were investigated under simulated gastrointestinal conditions. Theirmolecular weights were one sixth or one tenth that of Alg and the diffraction patterns of thehydrolysates resembled that of Alg. The drug release rate from Alg-Ca coated with GBapparently lowered than that of Alg-Ca (coating-free) in the gastric juice (pH1.2). And thecoating did not resist the disintegration of Alg-Ca in the intestinal juice (pH 6.8) and thegel erosion accelerated the drug release. On the other hand, for the coated Alg-Cacontaining chitosan, the drug release showed zero-order kinetics without rapid erosion ofAlg-Ca. The drug release rate from Alg-Ca was able to be controlled by the coating andmodifying the composition of the gel matrix. Full article

(This article belongs to the Special Issue Prodrugs)

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104 KiB

Open AccessArticle

Hantzsch Synthesis of 2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(o-methoxyphenyl)-1,4-dihydropyridine; a Novel Cyclisation Leading to an Unusual Formation of 1-Amino-2-methoxycarbonyl-3,5-bis(o-methoxyphenyl)-4-oxa-cyclohexan-1-ene

by Mirela Filipan-Litvić, Mladen Litvić, Ivica Cepanec and Vladimir Vinković

Molecules 2007, 12(11), 2546-2558; https://doi.org/10.3390/12112546 - 26 Nov 2007

Cited by 32 | Viewed by 17279

Abstract

Hantzsch condensation of two equivalents of methyl-3-aminocrotonate with (m-and p)-methoxybenzaldehyde afforded the expected products 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(m-methoxyphenyl)-1,4-dihydropyridine and 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(p-methoxyphenyl)-1,4-dihydropyridine, whereas o-methoxy-benzaldehyde produced mainly 1-amino-2-methoxycarbonyl-3,5-bis(o-methoxy-phenyl)-4-oxa-cyclohexan-1-ene. The structure of the product, not previously reported in theliterature, was determined by 1D and 2D NMR spectra and its MS [...] Read more.

Hantzsch condensation of two equivalents of methyl-3-aminocrotonate with (m-and p)-methoxybenzaldehyde afforded the expected products 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(m-methoxyphenyl)-1,4-dihydropyridine and 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(p-methoxyphenyl)-1,4-dihydropyridine, whereas o-methoxy-benzaldehyde produced mainly 1-amino-2-methoxycarbonyl-3,5-bis(o-methoxy-phenyl)-4-oxa-cyclohexan-1-ene. The structure of the product, not previously reported in theliterature, was determined by 1D and 2D NMR spectra and its MS fragmentation. This isthe first example of cyclisation leading to a substituted pyran rather than 1,4-DHP undertypical Hantzsch reaction conditions. A plausible mechanism for its formation ispostulated. Full article

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85 KiB

Open AccessArticle

Synthesis of New L-Ascorbic Ferulic Acid Hybrids

by Anne Sophie Voisin-Chiret, Marc-Antoine Bazin, Jean-Charles Lancelot and Sylvain Rault

Molecules 2007, 12(11), 2533-2545; https://doi.org/10.3390/12112533 - 17 Nov 2007

Cited by 21 | Viewed by 13601

Abstract

A feasibility and chemical study of the coupling conditions of L-ascorbic acidwith ferulic acid derivatives are described on the basis of the known synergistic effects ofmixtures of various antioxidants. Novel L-ascorbic ferulic hybrids linked at the C-3hydroxyl group were prepared with the aim [...] Read more.

A feasibility and chemical study of the coupling conditions of L-ascorbic acidwith ferulic acid derivatives are described on the basis of the known synergistic effects ofmixtures of various antioxidants. Novel L-ascorbic ferulic hybrids linked at the C-3hydroxyl group were prepared with the aim to protect the alcohol function and the enediolsystem. Full article

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461 KiB

Open AccessArticle

Comparative Study of Regioselective Synthesis of β-Aminoalcohols under Solventless Conditions Catalyzed by Sulfated Zirconia and SZ/MCM-41

by Guillermo Negrón-Silva, C. Xochitl Hernández-Reyes, Deyanira Angeles-Beltrán, Leticia Lomas-Romero, Eduardo González-Zamora and Juan Méndez-Vivar

Molecules 2007, 12(11), 2515-2532; https://doi.org/10.3390/12112515 - 15 Nov 2007

Cited by 21 | Viewed by 11616

Abstract

Sulfated zirconia and SZ/MCM-41 were used as catalysts for the synthesis of β-aminoalcohols via epoxide aminolysis. Sulfated zirconia was prepared by sol-gel andSZ/MCM-41 was obtained by impregnation. Solid catalysts were characterized by XRD,SEM-EDS, UV-Vis, FT-IR pyridine desorption and Nitrogen physisorption. Both acidmaterials were [...] Read more.

Sulfated zirconia and SZ/MCM-41 were used as catalysts for the synthesis of β-aminoalcohols via epoxide aminolysis. Sulfated zirconia was prepared by sol-gel andSZ/MCM-41 was obtained by impregnation. Solid catalysts were characterized by XRD,SEM-EDS, UV-Vis, FT-IR pyridine desorption and Nitrogen physisorption. Both acidmaterials were useful as catalysts, even when they were recycled several times. The β-aminoalcohols were characterized by FT-IR, ¹H- and ¹³C-NMR and GC-MS. Full article

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130 KiB

Open AccessArticle

Synthesis and Molecular Structure of Ethyl [N-tosyl-(R)-prolyloxy]-2(S)-[4-cyano-8,8-ethylenedioxy-5-oxo-5,6,7,8-tetrahydroindolizin-3-yl] Acetate, a Key Intermediate in the Total Synthesis of (20S)-Camptothecins

by Yun-Yan Kuang and Fen-Er Chen

Molecules 2007, 12(11), 2507-2514; https://doi.org/10.3390/12112507 - 13 Nov 2007

Cited by 2 | Viewed by 8454

Abstract

The synthesis of optically active [N-tosyl-(R)-prolyloxy]-2(S)-[4-cyano-8,8-ethylenedioxy-5-oxo-5,6,7,8-tetrahydroindolizin-3-yl] acetate (4a), a key intermediate forthe total asymmetric synthesis of 20(S)-camptothecin anticancer drugs, is described. Itsstructure was characterized by 2D-NMR techniques and the absolute configuration wasfurther confirmed for the first time by X-ray crystal structure analysis. Full article

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167 KiB

Open AccessReview

Cyclization-activated Prodrugs

by Paula Gomes, Nuno Vale and Rui Moreira

Molecules 2007, 12(11), 2484-2506; https://doi.org/10.3390/12112484 - 12 Nov 2007

Cited by 52 | Viewed by 18412

Abstract

Many drugs suffer from an extensive first-pass metabolism leading to druginactivation and/or production of toxic metabolites, which makes them attractive targets forprodrug design. The classical prodrug approach, which involves enzyme-sensitive covalentlinkage between the parent drug and a carrier moiety, is a well established [...] Read more.

Many drugs suffer from an extensive first-pass metabolism leading to druginactivation and/or production of toxic metabolites, which makes them attractive targets forprodrug design. The classical prodrug approach, which involves enzyme-sensitive covalentlinkage between the parent drug and a carrier moiety, is a well established strategy toovercome bioavailability/toxicity issues. However, the development of prodrugs that canregenerate the parent drug through non-enzymatic pathways has emerged as an alternativeapproach in which prodrug activation is not influenced by inter- and intraindividualvariability that affects enzymatic activity. Cyclization-activated prodrugs have beencapturing the attention of medicinal chemists since the middle-1980s, and reached maturityin prodrug design in the late 1990s. Many different strategies have been exploited in recentyears concerning the development of intramoleculary-activated prodrugs spanning fromanalgesics to anti-HIV therapeutic agents. Intramolecular pathways have also a key role intwo-step prodrug activation, where an initial enzymatic cleavage step is followed by acyclization-elimination reaction that releases the active drug. This wor Full article

(This article belongs to the Special Issue Prodrugs)

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64 KiB

Open AccessCommunication

A Novel Synthesis of Bromobenzenes Using Molecular Bromine

by Hamdi Özkan, Ali Dişli, Yılmaz Yıldırır and Lemi Türker

Molecules 2007, 12(11), 2478-2483; https://doi.org/10.3390/12112478 - 12 Nov 2007

Cited by 12 | Viewed by 10000

Abstract

Certain substituted bromobenzenes have been synthesized in acceptable yieldsusing a novel Sandmeyer type reaction. The reactions are relatively quick and possiblyproceed via a radical mechanism. Full article

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81 KiB

Open AccessArticle

Synthesis and Biological Activity of N-Substituted-3-chloro-2-azetidinones

by Ameya A. Chavan and Nandini R. Pai

Molecules 2007, 12(11), 2467-2477; https://doi.org/10.3390/12112467 - 12 Nov 2007

Cited by 87 | Viewed by 10498

Abstract

2-Aminobenzothiazole-6-carboxylic acid (1), on condensation with chloroacetylchloride yielded 2-(2-chloroacetylamino)benzothiazole-6-carboxylic acid (2), which onamination with hydrazine hydrate yielded in turn 2-(2-hydrazinoacetylamino)benzo-thiazole-6-carboxylic acid (3). Compound 3, on condensation with various aromaticaldehydes afforded a series of 2-{2-[N’-(arylidene)hydrazino]acetylamino}benzothiazole-6-carboxylic acids 4a-h, which upon dehydrative annulation in the presence [...] Read more.

2-Aminobenzothiazole-6-carboxylic acid (1), on condensation with chloroacetylchloride yielded 2-(2-chloroacetylamino)benzothiazole-6-carboxylic acid (2), which onamination with hydrazine hydrate yielded in turn 2-(2-hydrazinoacetylamino)benzo-thiazole-6-carboxylic acid (3). Compound 3, on condensation with various aromaticaldehydes afforded a series of 2-{2-[N’-(arylidene)hydrazino]acetylamino}benzothiazole-6-carboxylic acids 4a-h, which upon dehydrative annulation in the presence ofchloroacetyl chloride and triethylamine yielded 2-{2-[3-chloro-2-(aryl)-4-oxoazetidin-1-ylamino]-acetylamino}benzothiazole-6-carboxylic acids 5a-h. The synthesized compounds4a-h and 5a-h were screened for their antibacterial activity against four microorganisms:Staphylococcus aureus (Gram positive), Bacillus subtilis (Gram positive), Psuedomonasaeruginosa (Gram negative) and Escherichia coli (Gram negative). They were found toexhibit good to moderate antibacterial activity. The antifungal activity of these compoundswere also tested against three different fungal species. None of them were active againstthe species tested. Full article

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69 KiB

Open AccessArticle

Syntheses of Calix[4]Pyrroles by Amberlyst-15 Catalyzed Cyclocondensations of Pyrrole with Selected Ketones

by Shive Murat Singh Chauhan, Bhaskar Garg and Tanuja Bisht

Molecules 2007, 12(11), 2458-2466; https://doi.org/10.3390/12112458 - 9 Nov 2007

Cited by 27 | Viewed by 11041

Abstract

A facile and efficient protocol is reported for the synthesis of calix[4]pyrrolesand N-confused calix[4]pyrroles in moderate to excellent yields by reaction of dialkyl orcycloalkyl ketones with pyrrole catalyzed by reusable Amberlyst^TM-15 under eco-friendlyconditions. Full article

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91 KiB

Open AccessArticle

Synthesis and Bioevaluation of 5-Fluorouracil Derivatives

by Zhi-Yong Tian, Gang-Jun Du, Song-Qiang Xie, Jin Zhao, Wen-Yuan Gao and Chao-Jie Wang

Molecules 2007, 12(11), 2450-2457; https://doi.org/10.3390/12112450 - 6 Nov 2007

Cited by 31 | Viewed by 13206

Abstract

A series of six novel 5-fluorouracil derivatives 1-6 were synthesized and theirstructures confirmed by ¹H- and ¹³C-NMR, MS and elemental analysis. The preliminary invitro antitumor activities against B16, K562 and CHO cells and the in vivo inhibitions ofliver cancer H₂₂ [...] Read more.

A series of six novel 5-fluorouracil derivatives 1-6 were synthesized and theirstructures confirmed by ¹H- and ¹³C-NMR, MS and elemental analysis. The preliminary invitro antitumor activities against B16, K562 and CHO cells and the in vivo inhibitions ofliver cancer H₂₂ demonstrated that some of these compounds effectively inhibit the growthof tumor cells, but the in vivo trials in mice revealed that the compounds also exhibitedserious liver and lung tissue toxicity. The hydrolysis experiments indicated that this type ofcompound did not readily liberate 5-fluorouracil, as expected. Full article

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176 KiB

Open AccessArticle

Dopamine-Imprinted Polymers: Template-Monomer Interactions, Analysis of Template Removal and Application to Solid Phase Extraction

by Piotr Luliński, Dorota Maciejewska, Magdalena Bamburowicz-Klimkowska and Mirosław Szutowski

Molecules 2007, 12(11), 2434-2449; https://doi.org/10.3390/12112434 - 1 Nov 2007

Cited by 50 | Viewed by 10283

Abstract

A dopamine-imprinted polymer (MIP) was prepared in aqueous methanolsolution at 60^oC by free-radical cross-linking polymerization of methacrylic acid in thepresence of ethylene glycol dimethacrylate as the cross-linker and dopamine hydrochlorideas the template molecule. Its ability to isolate dopamine was evaluated as [...] Read more.

A dopamine-imprinted polymer (MIP) was prepared in aqueous methanolsolution at 60^oC by free-radical cross-linking polymerization of methacrylic acid in thepresence of ethylene glycol dimethacrylate as the cross-linker and dopamine hydrochlorideas the template molecule. Its ability to isolate dopamine was evaluated as the basis of asolid phase extraction procedure and compared with that of a non-imprinted polymer(NIP). The binding of dopamine was 84.1% and 29.1% for MIP and NIP, respectively.Various reported post-polymerization treatments to reduce template bleeding wereexamined. In our case the lowest bleeding was achieved after applying a combinedprocedure: continuous extraction in a Soxhlet apparatus (CE), followed by microwave-assisted extraction (ME) to a level of 0.061 μg/mL. A simplified model of the template-monomer complexes allowed rationalization of monomer choice based on the heats ofcomplex formation at a PM3 level of theory. Full article

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Molecules, Volume 12, Issue 11 (November 2007) – 11 articles , Pages 2434-2566

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