The preparation and antioxidant activity of the sulfanilamide derivatives of chitosan and chitosan sulfates

Chitosan (CS) and chitosan sulfates (CSS) with different molecular weight (Mw) were reacted with 4-acetamidobenzene sulfonyl chloride to obtain sulfanilamide derivatives of chitosan and chitosan sulfates (LSACS, HSACS, LSACSS, HSACSS). The preparation conditions such as different reaction time, temperature, solvent, and the molar ratio of reaction materials are discussed in this paper. Their structures were characterized by FTIR spectroscopy and elemental analyses. The antioxidant activities of the derivatives were investigated employing various established in vitro systems, such as hydroxyl-radical ((*)OH) superoxide anion (O2(*-)) scavenging and reducing power. All kinds of the compounds (HCS, LCS, HCSS, LCSS, HSACS, LSACS, HSACSS, LSACSS) showed stronger scavenging activity on hydroxyl radical than ascorbic acid (Vc). The inhibitory activities of the derivatives toward superoxide radical by the PMS-NADH system were obvious. The experiment showed that the superoxide radical scavenging effect of sulfanilamide derivatives of chitosan and chitosan sulfates was stronger than that of original CS and CSS. All of the derivatives were efficient in the reducing power. The results indicated that the sulfanilamide group were grafted on CS and CSS increased the reducing power of them obviously.     

Novel derivatives of chitosan and their antifungal activities in vitro

Three kinds of Schiff bases of carboxymethyl chitosan (CMCTS) were prepared, and their antifungal activities were assessed according to Jasso de Rodríguez's method. The results indicated that 2-(2-hydroxybenzylideneamino)-6-carboxymethylchitosan (HNCMCTS) and 2-(5-chloro-2-hydroxybenzylideneamino)-6-carboxymethylchitosan (HCCMCTS) had better inhibitory effects than those of chitosan or CMCTS against Fusarium oxysporium f. sp. vasinfectum, Alternaria solani, and Valsa mali.     

Preparation, characterization and antifungal properties of 2-(α-arylamino phosphonate)-chitosan

In this paper, 20 kinds of different 2-(α-arylamino phosphonate)-chitosan (2-α-AAPCS) were prepared by different Schiff bases of chitosan (CS) reacted with di-alkyl phosphite in benzene solution. The structures of the derivatives (2-α-AAPCS) were characterized by FT-IR spectroscopy and elemental analysis. In addition, the antifungal activities of the derivatives against four kinds of fungi were evaluated in the experiment. The results indicated that all the prepared 2-α-AAPCS had a significant inhibiting effect on the investigated fungi when the derivatives concentration ranged from 50 to 500 μg mL⁻¹. Furthermore, the antifungal activities of the derivatives increased with increasing the molecular weight and concentration. And the antifungal activities of the derivatives were affected by their dimensional effect and charge density. Besides, the rule and mechanism of the antifungal activities of them were discussed in this paper.     

Syntheses and Biological Activities of Dihydro-5,6-dehydrokawain Derivatives

The syntheses and biological activities of dihydro-5,6-dehydrokawain derivatives against plant pathogenic fungi and termites were investigated. Dihydro-5,6-dehydrokawain was isolated by a simple method without chromatography from the leaves of Alpinia speciosa K. Schum. The white crystalline compound obtained was identified as dihydro-5,6-dehydrokawain (1) by instrumental analyses. 4-Hydroxy-6-(2-phenylethyl)-2H-pyran-2-one (3) was prepared by hydrolyzing dihydro-5,6-dehydrokawain. Three dihydro-5,6-dehydrokawain derivatives were synthesized by reacting 3 with phosphoric agents.

Among the synthesized compounds, dimethyl [6-(2-phenylethyl)-2-oxo-2H-pyran-4-yl] phosphorothionate (4) had the strongest antifungal activity of 91% at 100 ppm against Corticium rolfsii.     

A concise synthesis of 4-nitrophenyl 2-azido-2-deoxy- and 2-acetamido-2-deoxy-D-mannopyranosides

4-nitrophenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha- and beta-D-mannopyranosides were prepared from methyl 4,6-O-benzylidene-alpha-D-glucopyranoside and 1,3,4,6-tetra-O-acetyl-alpha-D-glucopyranose, respectively. Chemoselective reduction of both azides with hydrogen sulfide readily afforded 4-nitrophenyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-alpha-D- and -beta-D-mannopyranosides in higher yields than reduction with triphenylphosphine or a polymer-supported triarylphosphine. Subsequent de-O-acetylation yielded 4-nitrophenyl 2-acetamido-2-deoxy-alpha-D-mannopyranoside and 4-nitrophenyl 2-acetamido-2-deoxy-beta-D-mannopyranoside in 20% and 44% overall yields, respectively.     

Synthesis,characterization and antifungal activity of quaternary derivatives of chitosan on Aspergillus flavus

Two series of new chitosan derivatives were synthesized by reaction of deacetylated chitosan (CH) with propyl (CH-Propyl) and pentyl (CH-Pentyl) trimethylammonium bromides to obtain derivatives with increasing degrees of substitution (DS). The derivatives were characterized by ¹H NMR and potentiometric titration techniques and their antifungal activities on the mycelial growth of Aspergillus flavus were investigated in vitro. The antifungal activities increase with DS and the more substituted derivatives of both series, CH-Propyl and CH-Pentyl, exhibited antifungal activities respectively three and six times higher than those obtained with commercial and deacetylated chitosan. The minimum inhibitory concentrations (MIC) were evaluated at 24, 48 and 72 h by varying the polymer concentration from 0.5 to 16 g/L and the results showed that the quaternary derivatives inhibited the fungus growth at polymer concentrations four times lower than that obtained with deacetylated chitosan (CH). The chitosans modified with pentyltrimethylammonium bromide exhibited higher activity and results are discussed taking into account the degree of substitution (DS).     

Antifungal efficacy of chitosan and its thiourea derivatives upon the growth of some sugar-beet pathogens

Chitosan (CS) was modified by reaction with benzoyl thiocyanate to give a thiourea derivative (TUCS). The antifungal behavior of chitosan and its thiourea derivative was investigated in vitro on the mycelial growth, sporulation and germination of conidia or sclerotia of the following sugar-beet: Beta vulgaris pathogens isolated in Egypt, Rhizoctonia solani Kühn (AG(2-2)) Sclerotium rolfsii Sacc. and Fusarium solani (Mart.) Sacc. All the prepared thiourea derivatives had a significant inhibiting effect on the different stages of development on the germination of conidia or sclerotia of all the investigated fungi in the polymer concentration range of 5-1000 microg ml(-1). In the absence of chitosan and its derivative, R. solani exhibited the fastest growth of the fungi studied. However, growth tolerance of the modified chitosan was highest for F. solani and lowest for R. solani. The most sensitive to the modified chitosan stress with regard to their germination and number produced were the sclerotia of S. rolfsii. It has been found that the TUCS is a much better fungicidal agent (about 60 times more) than the pure CS against most of the fungal strains tested. The molecular weight and the degree of deacetylation were found to have an important effect on the growth activities of the pathogens.     

Thermal decomposition of β-d-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-d-hexopyranoses under neutral conditions

β-d-Galactopyranosyl-(1→3)-2-acetamido-2-deoxy-d-glucose (LNB) and β-d-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-d-galactose (GNB) decompose rapidly upon heating into d-galactose and mono-dehydrated derivatives of the corresponding 2-acetamido-2-deoxy-d-hexoses, including 2-acetamido-2,3-dideoxy-hex-2-enofuranoses and bicyclic 2-acetamido-3,6-anhydro-2-deoxy-hexofuranoses. The decomposition is conducted under neutral conditions where glycosyl linkages are generally believed to be stable. The half-lives of LNB and GNB were 8.1 min and 20 min, respectively, at 90 °C and pH 7.5. The pH dependency of decomposition rates suggests that the instabilities are an extension of the conditions for the peeling reaction, often observed with glycans of O-linked glycoproteins under alkaline conditions. Such decomposition under the neutral conditions is commonly observed with 3-O-linked reducing aldoses.     

Synthesis of acyl thiourea derivatives of chitosan and their antimicrobial activities in vitro

Three different acyl thiourea derivatives of chitosan (CS) were synthesized and their structures were characterized by FT-IR spectroscopy and elemental analysis. The antimicrobial behaviors of CS and its derivatives against four species of bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Sarcina) and four crop-threatening pathogenic fungi (Alternaria solani, Fusarium oxysporum f. sp. vasinfectum, Colletotrichum gloeosporioides (Penz.) Saec, and Phyllisticta zingiberi) were investigated. The results indicated that the antimicrobial activities of the acyl thiourea derivatives are much better than that of the parent CS. The minimum value of MIC and MBC of the derivatives against E. coli was 15.62 and 62.49 microg/mL, respectively. All of the acyl thiourea derivatives had a significant inhibitory effect on the fungi in concentrations of 50-500 microg/mL; the maximum inhibitory index was 66.67%. The antifungal activities of the chloracetyl thiourea derivatives of CS are noticeably higher than the acetyl and benzoyl thiourea derivatives. The degree of grafting of the acyl thiourea group in the derivatives was related to antifungal activity; higher substitution resulted in stronger antifungal activity.     

Immobilization of a protease on modified chitosan beads for the depolymerization of chitosan

Neutral protease was immobilized on chitosan (CS), carboxymethyl chitosan (CMCS), and N-succinyl chitosan (NSCS) hydrogel beads. And the biocatalysts obtained were used to prepare low molecular weight chitosan (LMWC) and chitooligomers. Weight-average molecular weight of LMWC produced by neutral protease immobilized on CS, CMCS and NSCS hydrogel beads were 3.4 kDa, 3.2 kDa and 1.9 kDa, respectively. The effects of immobilization support and substrate on enzymatic reaction were analyzed by measuring classical Michaelis-Menten kinetic parameters. The FT-IR, XRD and potentiometric determination results indicated decrease of molecular weight led to transformation of crystal structure, but the degree of N-deacetylation and chemical structures of residues were not changed compared to initial chitosan. The degree of polymerization of chitooligomers was mainly from 2 to 7. We observed a strong dependence of the immobilized enzyme properties on the chemical nature of the supports, which leads to different microenvironment of neutral protease and changes the hydrolyzing process.     

Preparation and antimicrobial activity of some carboxymethyl chitosan acyl thiourea derivatives

Acetyl, chloroacetyl and benzoyl thiourea derivatives of carboxymethyl chitosan (ATUCMCS, CATUCMCS, and BZTUCMCS) with comparable grafting degree were synthesized and their structures were characterized by FTIR spectroscopy and elemental analyses. The antimicrobial behaviors of CMCS and its derivatives against three types of bacteria [Bacillis subtilis (B. subtilis), Staphylococous aureus (S. aureus) and Escherichia coli (E. coli)] and three crop-threatening pathogenic fungi [Aspergillus fumigate (A. fumigate), Geotrichum candidum (G. candidum) and Candida albicans (C. albicans)] were investigated. The results indicated that the antibacterial and the antifungal activities of the acyl thiourea derivatives are much higher than that of the parent CMCS. The acyl thiourea derivatives were more potent in case of Gram-positive bacteria than Gram-negative bacteria. This is illustrated for example by the values of minimum inhibitory concentration (MIC) of the ATUCMCS, CATUCMCS and BZTUCMCS against B. subtilis were 3.9, 15.6 and 62.5, respectively, while the MIC values of these derivatives against E. coli were 62.5, 125 and 500. Moreover, the antifungal activity of the CATUCMCS is higher than that of the acetyl and benzoyl thiourea derivatives. This may be due to the presence of chlorine atom.     

Preparation and characterisation of chitosans with oligosaccharide branches

The trimer 2-acetamido-2-deoxy-D-glucopyranosyl-beta-(1-->4)-2-acetamido-2-deoxy-D-glucopyranosyl-beta-(1-->4)-2,5-anhydro-D-mannofuranose (A-A-M) was reductively N-alkylated onto a fully de-N-acetylated chitosan (F(A)<0.001, DP(n)=25) to obtain branched chitosans with degree of substitution (DS) of 0.070, 0.23 and 0.40, as determined by 1H NMR spectroscopy. The apparent pK(a) values of the primary and secondary amines of the chitosans substituted with the trimer A-A-M were determined by monitoring the chemical shift of the H-2 of GlcN, and were determined as 6.5-6.9 for the primary (unsubstituted) amines and as 5.0-5.2 for the secondary (substituted) amines. The intrinsic pK(a) values (pK(int)) were found to be 7.3-7.4 for the substituted and 8.7 for the unsubstituted amines. The chitosan branched with A-A-M (DS 0.40) was found to be soluble in aqueous solution over the entire pH range. SEC-MALLS (size-exclusion chromatography with a multi-angle laser light scattering detector) further showed that addition of branches did not affect the molar hydrodynamic volume of the chitosan.     

Synthesis, characterization, and antifungal activity of novel quaternary chitosan derivatives

Three novel quaternary chitosan derivatives were successfully synthesized by reaction of chloracetyl chitosan (CACS) with pyridine (PACS), 4-(5-chloro-2-hydroxybenzylideneamino)-pyridine (CHPACS), and 4-(5-bromo-2-hydroxybenzylideneamino)-pyridine (BHPACS). The chemical structure of the prepared chitosan derivatives was confirmed by Fourier transform infrared (FT-IR) and ¹³C nuclear magnetic resonance (¹³C NMR) and their antifungal activity against Cladosporium cucumerinum, Monilinia fructicola, Colletotrichum lagenarium, and Fusarium oxysporum was assessed. Comparing with the antifungal activity of chitosan, CACS, and PACS, CHPACS and BHPACS exhibited obviously better inhibitory effects, which should be related to the synergistic reaction of chitosan itself with the grafted 2-[4-(5-chloro-2-hydroxybenzylideneamino)-pyridyl]acetyl and 2-[4-(5-bromo-2-hydroxybenzylideneamino)-pyridyl]acetyl.     

Effect of carboxymethylation conditions on the water-binding capacity of chitosan-based superabsorbents

A superabsorbent polymer (SAP) from chitosan was provided via carboxymethylation of chitosan, followed by cross-linking with glutaraldehyde and freeze-drying. This work was focused on an investigation of the effects of monochloroacetic acid (MCAA), sodium hydroxide, and reaction time on preparation of carboxymethyl chitosan (CMCS). The CMCS products were characterized using FTIR spectroscopy, and their degrees of substitution (DS) were measured using conductimetry and FTIR analysis. The highest DS value was obtained when the carboxymethylation reaction was carried out using 1.75 g MCAA and 1.75 g NaOH per g of chitosan in 4 h. The water solubilities of the CMCS products at various pHs were also evaluated, and the results indicated a significant impact of the reaction parameters on the solubility of CMCS. The CMCSs with the highest DS value resulted in SAPs having the highest water-binding capacity (WBC). The WBC of the best SAP measured after 10 min exposure in distilled water, 0.9% NaCl solution, synthetic urine, and artificial blood was 104, 33, 30, and 57 g/g, respectively. The WBC of this SAP at pH 2-9 passed a maximum at pH 6.     

In vitro evaluation of the biomedical properties of chitosan and quaternized chitosan for dental applications

The aim of this study was to evaluate the potential dental applications of chitosan (CS) and N-[1-hydroxy-3-(trimethylammonium)propyl]chitosan chloride (HTCC). HTCC was prepared by reacting CS with glycidyltrimethylammonium chloride (GTMAC). CS and HTCC were characterized by infrared (FITR) and ¹H NMR spectroscopy. The antibacterial activity of CS and HTCC against oral pathogens, their proliferation activity and effects on the ultrastructure of human periodontal ligament cells (HPDLCs) were investigated. The results indicated that four oral strains were susceptible to CS and HTCC with minimum inhibitory concentrations (MICs) ranging from 0.25 to 2.5 mg/mL. The in vitro 3-(4,5-dimethyl-2-thizolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay determined that CS at 2000, 1000, 100, and 50 μg/mL could stimulate the proliferation of HPDLCs. Instead, HTCC inhibited the proliferation at the same concentrations but accelerated the proliferation of HPDLCs at relatively low concentrations (10, 3, 1.5, 1, and 0.3 μg/mL). Transmission electron microscopy (TEM) observations revealed that the ultra-architecture of HPDLC was seriously destroyed by HTCC treatment at 1000 μg/mL. Taken together, these results contribute information necessary to enhance our understanding of CS and HTCC in the dental field.     

Preparation and antimicrobial activity of hydroxypropyl chitosan

Water-soluble hydroxypropyl chitosan (HPCS) derivatives with different degrees of substitution (DS) and weight-average molecular weight (Mw) were synthesized from chitosan and propylene epoxide under basic conditions. Their structure was characterized by IR spectroscopy, NMR spectroscopy, and elemental analysis, which showed that both the OH groups at C-6 and C-3 and the NH2 group of chitosan were alkylated. The DS value of HPCS ranged from 1.5 to 3.1 and the Mw was between 2.1x10(4) and 9.2x10(4). In vitro antimicrobial activities of the HPCS derivatives were evaluated by the Kirby-Bauer disc diffusion method and the macrotube dilution broth method. The HPCS derivatives exhibited no inhibitory effect on two bacterial strains (Escherichia coli and Staphylococcus aureus); however, some inhibitory effect was found against four of the six pathogenic fruit fungi investigated. Some derivatives (HPCS1, HPCS2, HPCS3, HPCS3-1, and HPCS4) were effective against C. diplodiella and F. oxysporum. HPCS3-1 is the most effective one with MIC values of 5.0, 0.31, 0.31, and 0.16mg/mL against A. mali, C. diplodiella, F. oxysporum, and P. piricola, respectively. Antifungal effects were also observed for HPCS2 and HPCS3-1 against A. mali, as well as HPCS3 and HPCS3-1 against P. piricola. The results suggest that relatively lower DS and higher Mw value enhances the antifungal activity of HPCS derivatives.     

Antiprotozoal activity of bicyclic diamines with a N-methylpiperazinyl group at the bridgehead atom

ω-Aminoacyl and -alkyl derivatives of 4-(4-methylpiperazin-1-yl)bicyclo[2.2.2]octan-2-amines and of 5-(4-methylpiperazin-1-yl)-2-azabicyclo[3.2.2]nonanes were prepared and their activities were examined in vitro against the multiresistant K₁ strain of Plasmodium falciparum and against Trypanosoma brucei rhodesiense (STIB 900). Some of the newly synthesized compounds showed very promising antiprotozoal activity and selectivity. A few of the alkylamino-2-azabicyclo[3.2.2]nonanes exhibited high antiplasmodial activity, whereas a single bicyclo[2.2.2]octane derivative was the most potent antitrypanosomal compound. The results of the newly synthesized compounds were compared with the activities of already synthesized compounds and of drugs in use. Structure–activity relationships were discussed.     

Ring-substituted quinolines. Part 2: Synthesis and antimycobacterial activities of ring-substituted quinolinecarbohydrazide and ring-substituted quinolinecarboxamide analogues

Additional structural modifications of the new chemical entity, 2,8-dicyclopentyl-4-methylquinoline (DCMQ; MIC = 6.25 μg/mL, M. tuberculosis H37Rv) resulted in the synthesis of four new series of the ring-substituted quinolinecarbohydrazides (series 1–4) constituting 22 analogues. All new derivatives were evaluated for in vitro antimycobacterial activities against drug-sensitive M. tuberculosis H37Rv strain. Certain ring-substituted-2-quinolinecarbohydrazide analogues described herein showed good inhibitory activity. In particular, analogues 4-(1-adamantyl)-2-quinolinecarbohydrazide (2d), 4,5-dicyclopentyl-2-quinolinecarbohydrazide (2e), 4,8-dicyclopentyl-2-quinolinecarbohydrazide (2f), and 4,5-dicyclohexyl-2-quinolinecarbohydrazide (2g) have exhibited the MIC value of 6.25 μg/mL. Further investigation of the most suitable lead prototype, 4-(1-adamantyl)-2-quinolinecarbohydrazide (2d, series 1) led to the synthesis of N2-alkyl/N2,N2-dialkyl/N2-aryl-4-(1-adamantyl)-2-quinolinecarboxamides (series 5) consisting of 13 analogues. Some of the synthesized carboxamides 7a, 7h, and 7m reported herein have exhibited excellent antimycobacterial activities in the range of 6.25–3.125 μg/mL against drug-sensitive and drug-resistant M. tuberculosis H37Rv strains.     

Synthesis of methylated chitosan containing aromatic moieties: Chemoselectivity and effect on molecular weight

N-Arylated chitosans were synthesized via Schiff bases formed by the reaction between the primary amino group of chitosan with aromatic aldehydes followed by reduction of the Schiff base intermediates with sodium cyanoborohydride. Treatment of chitosan containing N,N-dimethylaminobenzyl and N-pyridylmethyl substituents with iodomethane under basic conditions led to quaternized N-(4-N,N-dimethylaminobenzyl) chitosan and quaternized N-(4-pyridylmethyl) chitosan. Methylation occurred at either N,N-dimethylaminobenzyl and N-pyridylmethyl groups before the residual primary amino groups of chitosan GlcN units were substituted. The total degree of quaternization of each chitosan varied depending on the extent of N-substitution (ES) and the sodium hydroxide concentration used in methylation. Increasing ES increased the total degree of quaternization but reduced attack at the GlcN units. N,N-dimethylation and N-methylation at the primary amino group of chitosan decreased at higher ES’s. Higher total degrees of quaternization and degrees of O-methylation resulted when higher concentrations of sodium hydroxide were used. The molecular weight of chitosan before and after methylation was determined by gel permeation chromatography under mild acidic condition. The methylation of the N,N-dimethylaminobenzyl derivative with iodomethane was accompanied by numerous backbone cleavages and a concomitant reduction in the molecular weight of the methylated product was observed. The antibacterial activity of water-soluble methylated chitosan derivatives was determined using Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria; minimum inhibitory concentrations (MIC) of these derivatives ranged from 32 to 128 μg/mL. The presence of the N,N-dimethylaminobenzyl and N-pyridylmethyl substituents on chitosan backbone after methylation did not enhance the antibacterial activity against S. aureus. However, N-(4-N,N-dimethylaminobenzyl) chitosan with degree of quaternization at the aromatic substituent and the primary amino group of chitosan of 17% and 16–30%, respectively, exhibited a slightly increased antibacterial activity against E. coli.     

Cytokinins: Synthesis of 2-, 8-, and 2,8-substituted 6-(3-methyl-2-butenylamino)purines and their relative activities in promoting cell growth

We have synthesized 2- and 8-monosubstituted and 2,8-disubstituted derivatives of the cytokinin 6-(3-methyl-2-butenylamino)purine (N⁶-isopentenyladenine) and have shown the dependence of growth-promoting activity in the tobacco bioassay upon the position, number, and type of substituent. The representative substituent groups were MeS, Me, MeSO₂, C₆H₅CH₂S, HS and Cl. The 8-methyl derivative was exceptional in being more active than the unsubstituted parent compound. In general, substitution in the 8-position decreases activity less than substitution in the 2-position, with the exception of the electron-attracting methylsulfonyl. Substitution in both the 2- and 8-positions lowers the activity more than substitution at either single position on the adenine nucleus, with the exception of the 2,8-dimethyl derivative. The chloro and methylthio derivatives show activity in the same range as the methyl derivatives, and the mercapto compounds, which exist mainly as CS tautomers, show somewhat less activity than the corresponding methylthio compounds. Bulky (C₆H₅CH₂S and MeSO₂) and strongly electron-attracting (MeSO₂) substituents cause relatively great reduction in cytokinin activity.