Studies on saccharide benzimidazoles: 2-(ß-D-gulofuranosyl)benzimidazole and 2-(ß-D-glucofuranosyl)benzimidazole C-nucleoside analogs; synthesis, anomeric configuration and antifouling potency.

A series of acyclic 2-(D-gulo-) and 2-(D-gluco-)benzimidazole C-nucloside analogs have been prepared by condensation of o-phenylenediamine dihydrochloride derivatives with D-gulonic acid-γ-lactone and D-gluconic acid-γ-lactone, separately. Acid catalyzed dehydrative cyclization of the acyclic benzimidazole C-nucleoside afforded the corresponding 2-(ß-D-gulo-) and 2-(ß-D-gluco-)furanosyl benzimidazole C-nucleoside analogs. The structure and the anomeric configuration of C-nucleoside analogs obtained were determined by periodate oxidation, 1H NMR, UV and circular dichroism (CD) spectroscopy. The antifouling property of C-nucleoside analogs has been studied using antibacterial biofilm test. 2-(D-gulo-) and 2-(D-gluco-)benzimidazole analogs were useful for inhibiting marine bacterial growth and did not cause any bad effect to the surrounding seawater.

Synthesis of compounds having antimicrobial activity from alginate.

Compounds having antimicrobial activity were synthesized from sodium alginate, the main constituent of brown algae. Sodium alginate was oxidized with sodium periodate to get alginate dialdehyde (ADA). FTIR spectrum of the ADA gave very small peak characteristic for aldehyde groups at 1720 cm-1, indicating that the aldehyde group is masked somehow. It may be hydrated, involving at hemiacetal formation or hemialdol, similar to cellulose dialdehyde. Two methods were used for the condensation of ADA with o-phenylenediamine analogs to obtain the final products. The first method was stirring at room temperature and the second method was heating in microwave. The microwave method gave higher yield and shorter reaction time than the other method. The condensation reaction is considered as a shiff-base formation and the proposed mechanism was suggested. The condensation products were characterized by FTIR and UV spectra. The antimicrobial potency for five of these products in addition to the used alginate and to the precursor amines was evaluated against four pathogenic fungi and six pathogenic bacteria species.

Homo-C-nucleoside analogs IV. Synthesis of 4-(2,5-anhydro-D-altro-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole homo-C-nucleoside. CD assignment of the absolute configuration of the carbon bridge.

Dehydrative cyclization of 4-(D-altro-pentitol-1-yl)2-phenyl-2H-1,2,3-triazole in basic medium with one moler equivalent of p-toluene sulfonyl chloride in pyridine solution gave the homo-C-nucleoside 4-(2,5-anhydro-D-altro-1-yl)-2-phenyl-2H-1,2,3-triazole. The structure and anomeric configuration was determined by acylation, nuclear magnetic resonance (NMR), and mass spectroscopy. The stereochemistry at the carbon bridge of homo-C-nucleoside 2-phenyl-2H-1,2,3-triazoles was determined by circular dichroism (CD) spectroscopy.

Assessment of serum level of interleukin-1b and interleukin-12 in leprosy: impact of previous Bacillus Calmitte Guerin vaccination.

Macrophages play an important role in attempt to eliminate mycobacteria, via production of cytokines, including interleukin-1, and interleukin-12. Bacillus Calmitte Guerin (BCG) vaccination, known to induce interleukin-1ß in tuberculosis, was originally aimed at tuberculosis control, but it showed efficacy against leprosy. Our aim was to estimate serum levels of interleukin-1ß and interleukin-12, in leprosy, and to assess the impact of previous BCG vaccination on their levels. Serum interleukin-1ß and interleukin-12 p70 were estimated in 43 leprotic patients and 43 controls by enzyme-linked immunosorbent assay. Patients were grouped according to presence or absence of reactions, as well as bacillary load. Serum interleukin-1ß was significantly higher in patients as compared to controls (p = 0.047), and was significantly different in patients' groups (p = 0.036); with significantly higher level in multibacillary patients, both non reactional and with erythema nodosum leprosum, compared with paucibacillary/non reactional patients (p = 0.012 and 0.049 respectively). A statistically significant higher interleukin-1ß was found in BCG vaccinated paucibacillary patients as compared to unvaccinated patients (p = 0.031). Significantly elevated interleukin-12 was present in patients as compared to controls (p < 0.001), with no statistically significant difference comparing patients' groups. BCG vaccination showed stimulatory effect on monocytes only in the immunocompetent paucibacillary leprosy patients, as evidenced by higher Interleukin-1ß in this group. Interleukin-1ß was shown to have a pro-inflammatory role in multibacillary patients with or without erythema nodosum leprosum. Targeting interleukin-1ß may be promising to control episodic refractory erythema nodosum leprosum. Interleukin-12 may be a general marker of active Mycobacterium leprae infection.

Circular dichroism and anomeric configuration assignment of benzimidazole C-nucleoside analogs.

The circular dichroism of a series of acyclic polyhydroxyalkyl benzimidazole C-nucleoside analogs was correlated with the stereochemistry of the chiral carbon atom α to the benzimidazole base moiety. This correlation was used for the assignment of the anomeric configuration of 2-(ß-L-erythrofuranosyl) benzimidazole C-nucleoside analogs without a need to have the other anomer on hand, in a similar manner to the correlation obtained for assignment of the anomeric configuration of triazole C-nucleoside analogs.

Pattern of skin diseases in Cairo, Egypt.

BACKGROUND: Information on patterns of skin diseases in Egypt is scanty. METHODS: The medical records of patients attending dermatology outpatient clinics at Ain Shams University Hospitals from January 2001 to December 2001 were retrieved. Valid data of 7528 patients were included in the study. Demographic data (age and sex) and diagnoses of skin disease were extracted, coded, and analyzed. RESULTS: Patients' attendance revealed mean age of 23.5 ± 15.6 years and female predominance in a female to male ratio of 1.6:1. Most patients presented in summer (40.7%). Infections constituted most of the dermatoses (45.4%), and scabies was the most common disease (9.26%). Hypersensitivity diseases came after (22%) and, interestingly, the dermatitis subgroup (12.94%) followed fungal infections (15.83%) immediately, preceding other infection subgroups. Females predominated in most dermatoses. Urticaria predominated in infants, bacterial infections in preschool stage, fungal infections in school and young adult stages, and dermatitis in old adult and geriatric stages. Fungal infections predominated in all seasons. The peak presentation of all diseases was in summer except urticaria that was represented more in spring. CONCLUSION: Dermatitis preceded many infectious diseases as an index of the development and urbanization of a community. However, infections still represent the most common dermatoses. Fortunately, they are potentially controllable and, therefore, healthcare strategies that target infections may represent the key for an efficient national healthcare program.

Homo-C-nucleoside analogs III. Studies on the base-catalyzed dehydrative cyclization of 4-(d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole.

Treatment of 4-(d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole with one molar equivalent of 2,4,6-triisopropylbenzenesulfonyl chloride (TIBSCl) in pyridine solution afforded the homo-C-nucleoside analog; 4-(2,5-anhydro-d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole in 54% yield and 4-(α-d-arabinopyranosyl)-2-phenyl-2H1,2,3-triazole analog in 3% yield. The 4-(5-O-triisopropylbenzenesulfonyl)-d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole analog was isolated as an intermediate and identified as its tetra-O-acetyl derivative. The 4-(5-chloro-5-deoxy-d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole analog was isolated as a byproduct. The structure and anomeric configuration of the products were determined by acylation, NMR spectroscopy, and mass spectrometry.

CD and NMR assignment of the anomeric configuration of 4-(5-deoxy-alpha,beta-l-arabinofuranosyl)-2-phenyl-2H-1,2,3-triazole C-nucleoside analogs.

Acid-catalyzed dehydrative cyclization of 5-deoxy-L-manno-pentitol-1-yl)-2-heptulose bisphenylhydrazone and subsequent reflux with copper sulfate gave an anomeric mixture of 4-(5-deoxy-alpha,beta-L-arabinofuranosyl)-2-phenyl-2H-1,2,3-triazole C-nucleoside analogs. The mixture was separated by chromatography, and the anomeric compositions configurations of the components were determined by CD, NMR, mass spectroscopy, and acylation.

Synthesis of N-bridgehead heterocycles from saccharide benzimidazoles.

Treatment of D-arabino-tetritol-1-yl-benzimidazole with P-toluenesulfonyl chloride (1molequiv) in pyridine, afforded the N-bridgehead heterocycles, 2R,3R,4S-trihydroxy-1:2:3:4-tetrahydropyridino[1,2-a]benzimidazole. The structure of the latter compound was determined by acylation, (1)H, and (13)C NMR spectroscopy and mass spectrometry.

Circular dichroism as a reliable tool for anomeric assignment of glycosyl-2-phenyl-2H-1,2,3-triazole C-nucleoside analogs. A rule for prediction of their anomeric configuration.

The circular dichroism (CD) of a series of acyclic C-nucleoside analogs; 4-(pentahydroxypentyl-1-yl)-2-phenyl-2H-1,2,3-triazoles [1-5] and 4-(D-glycero-D-gulo)-2-phenyl-2H-1,2,3-triazole 6, are reported. A correlation between the sign of the Cotton effect at the maximal UV absorption and the absolute configuration of the carbon atom alpha- to the triazole base moiety is reported. The CD of anomeric 4-(alpha,beta-D-arabinofuranosyl)- and 4-(alpha,beta-D-arabinopyranosyl)-2-phenyl-2H-1,2,3-triazole C-nucleosides are reported. The assignment of the anomeric configuration of C-glycosyl-2-phenyl-2H-1,2,3-triazoles from their CD spectra was found to be a simple method that relies on comparison of the sign of the Cotton effect at the maximal UV absorption and the absolute configuration of the anomeric carbon atom. A correlation between the anomeric configuration and the sign of the Cotton effect at the maximal UV absorption is deduced and generalized as a rule for prediction of the anomeric configuration of C-glycosyl-2-phenyl-2H-1,2,3-triazoles. Nuclear Overhauser effect and 13C NMR spectra supported the CD assignment rule.

Studies on the dehydrative cyclization of epimeric 4-(L-xylo and L-lyxo-tetritol-1-yl)-2-phenyl-2H-1,2,3-triazoles. Circular dichroism and NMR assignment of the formed anomeric C-nucleoside L-threofuranosyl triazole analogs.

Dehydrative cyclization of epimeric 4-(L-xylo- and L-lyxo-tetritol-1-yl)-2-phenyl-2H-1,2,3-triazoles afforded the anomeric alpha and beta-L-threofuranosyl analogs. The anomeric configuration of the formed anomeric C-nucleoside analogs was determined by circular dichroism and NMR spectroscopy.

Characterization of the alginates from algae harvested at the Egyptian Red Sea coast.

The alginates from five species of brown algae from the Egyptian Red Sea coast, namely: Cystoseira trinode, Cystoseira myrica, Sargassum dentifolium, Sargassum asperifolium, and Sargassum latifolium, were isolated and their compositions and structures studied by 1H NMR spectroscopy. All the alginates studied contain more guluronic acid (G) than mannuronic acid (M) and have a homopolymeric block-type structure (eta<1). The intrinsic viscosity of the alginate samples range from 8.6 to 15.2 and the gel strength ranges from 10.97 to 15.51. The constitutional G- and M-blocks of alginates from two different species (C. trinode and S. latifolium) were separated after partial acid hydrolysis. The 1H NMR spectral data of the blocks GG and MM obtained by chemical fractionation were compared with those of polymeric alginates. The monomeric uronic acids were separated by complete acid hydrolysis of S. asperifolium alginate and the G and M monomers were characterized by 1H, 13C NMR spectroscopy as well as by paper electrophoresis.

Circular dichroism and the anomeric configuration of C-glycofuranosyl-2-phenyl-2H-1,2,3-triazoles.

Circular dichroism spectra of a series of 4-(tetra-hydroxy-tetryl-1-yl)2-phenyl-2H-1,2,3-triazoles were measured and the sign of their Cotton effects was correlated to the absolute configuration of the hydroxyl group alpha to the triazole base moiety. Those having the D-glycero-configuration in their Fischer projection formula show positive Cotton effect and those with the L-glycero-configuration show negative Cotton effect. This correlation was extended for the assignment of the anomeric configuration of the corresponding glycofuranosyl-C-nucleosides.