Biomedical subjects
Publications and source records attributed to H N ElSohly.
The indolopyridoquinazoline alkaloid, 3-hydoxyrutaecarpine, was isolated from Leptothyrsa sprucei, along with 8-methoxypsoralen, 5-methoxypsoralen, imperatorin, isoimperatorin, kaempferol 3-O-alpha-L-rhamnopyranoside, clematine and cnidioside B. The usefulness of the gradient 1H-15N HMBC NMR spectroscopy in the structure elucidation of 3-hydroxyrutaecarpine is noted.
Resolution of racemic 2-benzyl-2-hydroxy-1-benzofuran-3(2H)-ones (auronols) and CD data of the ensuing enantiomers permit assessment of the absolute configuration at the single stereocenter.
Four new alkaloids, nauclealines A (1) and B (2) and naucleosides A (3) and B (4), together with six known compounds, strictosamide (5), vincosamide (6), pumiloside (7), kelampayoside A, sitosterol, and sitosteryl beta-D-glucoside, were isolated from the bark of Nauclea orientalis. The structures of 1-4 were elucidated using 1D and 2D NMR spectral methods, including COSY, DEPT, HMQC, (13)C-(1)H HMBC, and (15)N-(1)H HMBC.
Assay-guided fractionation of the ethanol extract of the twigs and leaves of Miconia myriantha yielded two new compounds, mattucinol-7-O-[4' ',6' '-O-(S)-hexahydroxydiphenoyl]-beta-D-glucopyranoside (1) and mattucinol-7-O-[4' ',6' '-di-O-galloyl]-beta-D-glucopyranoside (2), along with mattucinol-7-O-beta-D-glucopyranoside (3), ellagic acid (4), 3,3'-di-O-methyl ellagic acid-4-O-beta-D-xylopyranoside, and gallic acid. Complete (1)H and (13)C NMR assignments of compound 1, which possesses a hexahydroxydiphenoyl unit, were achieved using the HMBC technique optimized for small couplings to enhance the four-bond and two-bond H/C correlations. Compounds 1 and 4 showed inhibitory effects against Candida albicans secreted aspartic proteases, with IC(50) of 8.4 and 10.5 microM, respectively.
A novel naphthopyrone derivative, named quinquangulone (1), has been isolated from Cassia quinquangulata, along with the known compounds quinquangulin (2) and its two glycosides (3 and 4), rubrofusarin (5) and its two glycosides (6 and 7), nor-rubrofusarin (8) and its 6-O-glucoside (9), and three stilbenes (10-12). The structure of quinquangulone was established by spectral interpretation as 5,9-dihydroxy-8-methoxy-2,9-dimethyl-6-oxo-4H,6H,9H-naphtho-[2,3-b]pyran-4-one. Reinvestigation of the NMR spectra of quinquangulin led to revision of its structure as 5,6-dihydroxy-8-methoxy-2,9-dimethyl-4H-naphtho[2,3-b]pyran-4-one (2a). The structures of two quinguangulin glycosides, 3 and 4, were also revised accordingly. Compound 2a exhibited activity against Staphylococcus aureus and methicillin-resistant S. aureus (MIC, 3.125 and 6.25 microg/mL, respectively).
Five prenylated flavonoids, including one new natural product, were isolated from an ethanol extract of the leaves of Maclura tinctoria (L.) Gaud. The new compound has been characterized as 2',4',4,2''-tetrahydroxy-3'-[3''-methylbut-3''-enyl]chalcone (1). The known compounds were identified as 2',4',4-trihydroxy-3'-[3''-methylbut-3''-enyl]chalcone (isobavachalcone) (2), 4,2'-dihydroxy-2''-[1-hydroxy-1-methylethyl]-2'',3''-dihydrofurano[4'',5'':3',4']chalcone (bakuchalcone) (3), 4,4',5''-trihydroxy-6'',6''-dimethyldihydropyrano[2'',3'':5',6'']chalcone (bavachromanol) (4), and 5,7,3',4'-tetrahydroxy-6,8-diprenylisoflavone (6,8-diprenylorobol) (5). All the isolated compounds were evaluated against the AIDS-related opportunistic fungal pathogens, Candida albicans and Cryptococcus neoformans. Compound 2 was active against both yeasts.
This research describes the identification of three new high molecular weight polysaccharide preparations isolated from food-grade microalgae that are potent activators of human monocytes/macrophages: "Immulina" from Spirulina platensis, "Immunon" from Aphanizomenon flos-aquae, and "Immurella" from Chlorella pyrenoidosa. These polysaccharides are structurally complex and have estimated molecular weights above ten million daltons. All three polysaccharides are highly water soluble and comprise between 0.5 % and 2.0 % of microalgal dry weight. Immunostimulatory activity was measured using a transcription factor-based bioassay for nuclear factor kappa B (NF-kappa B) activation in THP-1 human monocytes/macrophages. Using this system the EC(50) values for these microalgal polysaccharides are between 20 and 110 ng/ml (about 10pM). THP-1 activation was confirmed by measuring immune cytokine mRNA induction using reverse transcriptase-polymerase chain reaction (RT-PCR). Each polysaccharide substantially increased mRNA levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). These polysaccharides are between one hundred and one thousand times more active for in vitro monocyte activation than polysaccharide preparations that are currently used clinically for cancer immunotherapy.
Antifungal assay-guided isolation of the 95% ethanol extract of the stems of Colubrina retusa yielded jujubogenin 3-O-alpha-L-arabinofuranosyl(1-->2)-[beta-D-glucopyranosyl (1-->3)]-alpha-L-arabinopyranoside (1), which showed modest growth-inhibitory effects against Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus (MICs, 50 microg/mL). In addition, two new minor saponins, jujubogenin 3-O-alpha-L-arabinofuranosyl(1-->2)-[2-O-(trans, cis)p-coumaroyl-beta-D-glucopyranosyl(1-->3)]-alpha-L-arabinopy ranosi de (2), and jujubogenin 3-O-(5-O-malonyl)-alpha-L-arabinofuranosyl (1-->2)-[beta-D-glucopyranosyl(1-->3)]-alpha-L-arabinopyranoside (3), were obtained. Saponin 2 was marginally active against only C. neoformans, with a MIC of 50 microg/mL, while 3 was inactive. NMR spectroscopy was used extensively for the structure determination of these compounds. The previously reported ambiguity of the NMR assignments of jujubogenin saponins for carbons -26 to -29 was clarified by a comprehensive analysis of the NMR spectra of 1.
Two new auronols, amaronols A (1) and B (2), were isolated from the bark of Pseudolarix amabilis, along with pseudolaric acid B (3), pseudolaric acid C (4), demethoxydeacetoxy-pseudolaric acid B (5), pseudolaric acid B-beta-D-glucoside (6), pseudolaric acid A-beta-D-glucoside (7), and myricetin (8). The structures of amaronols A and B were established by spectral data interpretation as 2,4,6-trihydroxy-2-[(3',4',5'-trihydroxyphenyl) methyl]-3(2H)-benzofuranone and 2,4,6-trihydroxy-2-[(3', 5'-dihydroxy-4'-methoxyphenyl) methyl]-3(2H)-benzofuranone, respectively. Antimicrobial testing results of the eight compounds indicated that only pseudolaric acid B was active against Candida albicans (MIC, 3.125 microg/mL; MFC, 6.25 microg/mL), while myricetin was marginally active against Trichophyton mentagrophytes (MIC, 50 microg/mL).
A new jujubogenin saponin was isolated from the stems of Colubrina retusa and identified as jujubogenin 3-O-alpha-L-arabinofuranosyl (1-->2)-[3-O-(trans)-p-coumaroyl-beta-D-glucopyranosyl (1-->3)]-alpha-L-arabinopyranoside (4) on the basis of chemical and spectroscopic data. The antimycobacterial activity expressed as minimum inhibitory concentration (MIC) for compound 4 was 10 microg/mL.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Microbial metabolism studies of the antimalarial drug arteether (1) have shown that arteether is metabolized by a number of microorganisms. Large-scale fermentation with Aspergillus niger (ATCC 10549) and Nocardia corallina (ATCC 19070) have resulted in the isolation of four microbial metabolites which have been characterized using two-dimensional nuclear magnetic resonance (2D-NMR) techniques. These metabolites have been identified as "AEM1" (2), 3 alpha-hydroxydeoxyarteether (3), 3 alpha-hydroxydeoxydihydroartemisinin (4), and deoxydihydroartemisinin (5).
Microbial metabolism studies of the antimalarial drug arteether (1) have shown that arteether is metabolized to six new metabolites in addition to those previously reported (3). Large-scale fermentations with Cunninghamella elegans (ATCC 9245) and Streptomyces lavendulae (L-105) have resulted in the characterization of these metabolites primarily by two-dimensional nuclear magnetic resonance (2D-NMR) methods as 9 beta-hydroxyarteether (2), a ring rearrangement metabolite (3), 3 alpha-hydroxy-11-epi-deoxydihydroartemisinin (4), 9 alpha-hydroxyarteether (5), 2 alpha-hydroxyarteether (6), and 14-hydroxyarteether (7). Thermospray mass spectroscopy/high-performance liquid chromatographic analyses have shown that four of these metabolites (2, 5, 6, 7) are also present in rat liver microsome preparations.
Thermospray LC/MS methods with internal standardization were developed for the quantification of the antimalarial arteether and six of its metabolites at the 1-10 micrograms/ml level in liver microsome preparations without the use of solvent extraction. The thermospray mass spectra of arteether and most of its metabolites exhibited strong [M + NH4]+ and [M - OR]+ peaks arising from the molecular ion adduct and the loss of the alkoxy or hydroxy group of the side chain. In addition to the six metabolites for which authentic reference standards were available, three additional metabolites were detected. The major metabolites of arteether were found to be dihydroartemisinin, deoxydihydroartemisinin, 3-hydroxydeoxydihydroartemisinin, two isomers of hydroxyarteether, and 3-hydroxydeoxyarteether. Deoxyartheether was not found at significant concentrations in the microsome preparation.
The effects of cocaine, its metabolites, and other alkaloids from Erythroxylon coca on the primary immune responses of ICR mice to sheep red blood cells (sRBC) and dinitrofluorobenzene (DNFB) were studied. The Jerne hemolytic plaque assay (PFC) was used to evaluate the humoral immune response to sheep red blood cells, and the delayed type hypersensitivity (DTH) response to DNFB was used to study cellular immune responsiveness. Drugs were given in single daily po doses for 5 consecutive days beginning on the day of immunization or 3 days prior to and on Days 3 and 4 after immunization. Inhibition of both PFC and DTH responses occurred at doses of 15 to 60 mg/kg of cocaine and was greatest when fed during immunization. Five other alkaloids also suppressed the PFC and/or DTH response. Cocaine was more suppressive than the six other alkaloids tested. Ethanol (5 g/kg) did not suppress the DTH response and only marginally suppressed the PFC response. delta 9-THC inhibited the PFC response at doses of 10 mg/kg and marginally suppressed the DTH response at doses of 30 mg/kg, but not at other doses ranging from 10 to 90 mg/kg. Coadministration of 5 g/kg ethanol and 15 mg/kg cocaine resulted in 50% antagonism of effects of cocaine on the PFC response and complete antagonism of the suppression of the DTH response, but only if these substances were given during the period of immunization. Like ethanol, delta 9-THC also abolished the inhibitory effects of cocaine on the PFC and DTH response but only if coadministered during the period of immunization. Coadministration of ethanol and delta 9-THC resulted in synergistic inhibition of both DTH and PFC responses.
Two new dihydrostilbene compounds (named cannabistilbenes I and II) were isolated from a polar acidic fraction of a Panamanian variant of Cannabis sativa grown in Mississippi. The structure of cannabistilbene I was shown to be 3,4'-dihydroxy-5-methoxy-3'-(3-methylbut-2-enyl)-dihydrostilben e (1) from spectral data which was confirmed by synthesis. There is spectral evidence to indicate that cannabistilbene II could be represented by either structure 3 or 4.
Immunoassay procedures, both enzyme immunoassay and radioimmunoassay, continue to be widely used to screen samples for recent marijuana use by analyzing the urine samples for 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (11-nor-delta 9-THC-9-COOH) (the major urinary metabolite of delta 9-tetrahydrocannabinol [delta 9-THC]). Using commercially available immunoassay reagents, the cross-reactivity of the antiserum utilized in Abbott's TDx cannabinoid assay (a fluorescence polarization immunoassay) was evaluated. This cross-reactivity was evaluated against a group of cannabinoids and noncannabinoid phenolic constituents of Cannabis, some cannabinoid metabolites, and other agents that appear in normal urine samples. In general, the antiserum was equally reactive toward 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid, its glucuronide, and the corresponding delta 8-isomer, which was the acid moiety utilized in standards and controls of the assay prior to January, 1990. Reduced binding to the antiserum was observed with hydroxylated derivatives of delta 9- and delta 8-THC, and the other cannabinoids, in general, exhibited limited binding potentials toward the antibody. For the noncannabinoid constituents, no binding was observed at the highest concentrations evaluated (40 mg/L).