The mechanism of the antiulcer effect of omeprazole was studied placing emphasis on its role to block oxidative damage and apoptosis during ulceration. Dose-response studies on gastroprotection in stress and indomethacin-induced ulcer and inhibition of pylorus ligation-induced acid secretion indicate that omeprazole significantly blocks gastric lesions at lower dose (2.5 mg/kg) without inhibiting acid secretion, suggesting an independent mechanism for its antiulcer effect. Time course studies on gastroprotection and acid reduction also indicate that omeprazole almost completely blocks lesions at 1 h when acid inhibition is partial. The severity of lesions correlates well with the increased level of endogenous hydroxyl radical (⋅OH), which when scavenged by dimethyl sulfoxide causes around 90% reduction of the lesions, indicating that ⋅OH plays a major role in gastric damage. Omeprazole blocks stress-induced increased generation of ⋅OH and associated lipid peroxidation and protein oxidation, indicating that its antioxidant role plays a major part in preventing oxidative damage. Omeprazole also prevents stress-induced DNA fragmentation, suggesting its antiapoptotic role to block cell death during ulceration. The oxidative damage of DNA by ⋅OH generated in vitro is also protected by omeprazole or its analogue, lansoprazole. Lansoprazole when incubated in a ⋅OH-generating system scavenges⋅OH to produce four oxidation products of which the major one in mass spectroscopy shows a molecular ion peak atm/z 385, which is 16 mass units higher than that of lansoprazole (m/z 369). The product shows no additional aromatic proton signal for aromatic hydroxylation in 1H NMR. The product absorbing at 278 nm shows no alkaline shift for phenols, thereby excluding the formation of hydroxylansoprazole. The product is assigned to lansoprazole sulfone formed by the addition of one oxygen atom at the sulfur center following attack by the ⋅OH. Thus, omeprazole plays a significant role in gastroprotection by acting as a potent antioxidant and antiapoptotic molecule.

Chromatographic resolution of polyclonal antibodies is a challenging analytical problem and a successful method may have many applications. We have resolved polyclonal antibodies against testosterone 3-(O-carboxymethyl)oxime on a homologous testosterone-Sepharose matrix by using a ternary gradient system of propionate-1 M propionic acid-2 M propionic acid. Nineteen peaks were detected, sixteen of which were characterized by steroid binding activity and IgG assay. The relative affinities of the pooled fractions, determined by ELISA and by thiocyanate elution, correlated well with their retention times. The slopes of the displacement curves in antigen-immobilized testosterone ELISA increased with retention times of the fractions; testosterone required for 50% displacement being, 90, 5.8 and 24 ng/well for fraction I, fraction XVI and total antiserum, respectively. Cross-reactivity of the fractions towards 5alpha-dihydrotestosterone varied from 31 to 74% compared to 47% in the total antiserum.

We have developed an improved method, using 96-well microtiter plates, for the microbiological assay of folic acid. With this method, the tedium of conventional microbiological analysis is substantially decreased. Culture volumes have been reduced 33-fold, and pipetting procedures have been simplified. Assay time has been reduced to 14 h, and sensitivity has increased 10-fold (0.1 ng/mL). Analytical recoveries range from 98 to 104%. Intra-assay and interassay variabilities are less than 11%. The assay does not require extensive manipulation of inoculum. Day-to-day variability has been minimized by using saline aliquots of the bacterial suspension stored at 4 degrees C. The procedure is accurate, selective, and useful for direct measurement of folic acid in multivitamin formulations.

Interleukin-8, a neutrophil chemotactic agent causes excessive accumulation of the cells in a number of inflammatory diseases. The activity has been shown to be mediated through a specific functional receptor present on the surface of neutrophils. No information is available about the amino acids constituting the IL-8 binding domain of the receptor. Treatment of neutrophils with 5,5'-dithio-bis(2-nitrobenzoic acid), a thiol-specific modifier, at the concentrations of 0.4 mM and 1 mM reduced IL-8 binding ability and IL-8-induced migration of the cells by 45% and 65%, respectively. Dithiothreitol could regenerate the binding capacity and the ligand could protect the receptor from the effect of the reagent. All the evidence suggests that one or more critical thiol residues are located in the IL-8 binding site of the receptor which are indispensible for normal functions of IL-8.

Interleukin‐8, a neutrophi] chemotactic agent causes excessive accumulation of the cells in a number of inflammatory diseases. The activity has been shown to be mediated through a specific functional receptor present on the surface of neutrophils. No information is available about the amino acids constituting the IL‐8 binding domain of the receptor. Treatment of neutrophils with 5,5'‐dithio‐bis(2‐nitrobenzoic acid), a thiol‐specific modifier, at the concentrations of 0.4 mM and 1 mM reduced IL‐8 binding ability and IL‐8‐induced migration of the cells by 45% and 65%, respectively. Dithiothreitol could regenerate the binding capacity and the ligand could protect the receptor from the effect of the reagent. All the evidence suggests that one or more critical thiol residues are located in the IL‐8 binding site of the receptor which are indispensible for normal functions of IL‐8.

AbstractThe relative stereochemistry of the title compound (VI) is confirmed by its total synthesis starting from the amine (Ia) and 3‐acetylpyridine (II).

The structure of alamaridine (1) a novel benzopyridoquinolizine alkaloid, was established by spectral data. However, its stereochemistry could only be determined now by a total synthesis involving the key cyclisation of an 1-methyl-2-pyridylmethyl-3,4-dihydroisoquinolinium salt 19a in presence of pivaloyl chloride and triethylamine. O-Benzyldehydroalamaridine thus formed was reduced by sodium cyanoborohydride and then deprotected to obtain alamaridine (1) and 5-epi-alamaridine (26). Isoalamaridine (27) and its 5-epimer (28) were also synthesised following the same route.

A homogeneous enzyme immunoassay for estradiol estimation has been developed, which can be extended to other steroids. A new procedure for the preparation of estradiol -3-0- carboxymethyl ether by a simple one step reaction in high yield (90%) has been described. This hapten has been used for raising highly specific anti-estradiol antibody in rabbits and for preparation of enzyme conjugates. Two different enzymes, lysozyme and glucose -6- phosphate dehydrogenase have been studied for their suitability as enzyme labels. Our results indicate that lysozyme-conjugate meets the essential requirement for a practical enzyme immunoassay. The advantage of the present nonradioactive procedure is the overall simplicity, low cost and high stability of the reagents.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies on Indian Medicinal Plants, 87. Lacinilene C--A Rare Sesquiterpene from Alangium IamarckiiR. Mukhopadhyay, P. P. Ghosh Dastidar, E. Ali, and S. C. PakrashiCite this: J. Nat. Prod. 1987, 50, 6, 1185Publication Date (Print):November 1, 1987Publication History Published online1 July 2004Published inissue 1 November 1987https://pubs.acs.org/doi/10.1021/np50054a037https://doi.org/10.1021/np50054a037research-articleACS PublicationsRequest reuse permissionsArticle Views73Altmetric-Citations2LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

The synthesis of (±) -9-demethylprotoemetinol [(±) -3d] was accomplished by LiAlH4 reduction of the tricyclic ester (±) -5 and subsequent debenzylation of the resulting tricyclic alcohol (±) 10. Acetylation of (±) -3d with acetic anhydride and pyridine gave the diacetate (±) -11. The same sequence of reactions starting with (-) -5 afforded (-) -9-demethylprotoernetinol [(-) -3d] and the diacetate (-) -11 through (-) -10. Parallel synthetic routes starting with the isomeric tricyclic esters (±) -9 and (-) -9 produced (±) -and (-) -10-demethylprotoemetinols [(±) -4d and (-) -4d] and the corresponding diacetates [(±) -13 and (-) -13] through (±) -12 and (-) -12, respectively. The correctness of the structure and absolute stereochemistry of an Alangium alkaloid inferred to be 10-demethylprotoemetinol was confirmed by a direct comparison of its diacetate with synthetic (-) -13.

Three new stereoisomeric Steroidal alkaloids, viz. solacapine (6), episolacapine (11), and isosolacapine (13), along with another hitherto unreported base, O-methylsolanocapsine (3), have been isolated from the arboreal part of Solanum pseudocapsicum Linn. They have been characterised as (20S, 22R, 23S, 25R)-, (20S, 22R, 23R, 25R)-, and (20S, 22S, 23S, 25R)-3β-amino-16α,23-dihydroxy-22,26-epimino-5α-cholestanes, respectively, primarily based on 1H and 13C n.m.r. spectra. The structures of (3), (6), and (11) could be confirmed by correlation with solanocapsine (1). Isosolacapine (13) turned out to be the first 22,26-epiminocholestane derivative encountered in nature with 22βN stereochemistry. A diagnostic down-field shift of the C-22 resonance frequency in the 13C n.m.r. spectra of 22βN-22,26-epiminocholestanes by ca. 3 p.p.m. relative to those of the corresponding 22αN-isomers has been observed. The C-25 stereochemistry of solanogantamine (28) and isosolanogantamine (29), the stereoisomeric 3-amino solanidanes isolated from Solanum gigantem Jacq., has also been established.

The versatility of Alanaium lamarckii Thw.(Alangiaceae) in producing alkaloids is well-established.Thus, the so-called Ipecac alkaloids with varied substitution pattern in ring A, the isoquinoline -8-carboline hybrids,tkirbiogenetic intermediates and pyridobenzoquinolizine -a new class of alkaloids, 1 have earlier been reported from different parts of this plant.More 2 recently, we encountered a unique protoberberine alkaloid.bharatamine , devoid of any oxygen function in ring D clearly indicating its genesis from a monoterpenoid precursor, a pathway hitherto unknown.We now report yet an01 :her new biogenetically intere: idc quinolizine alkaloid designated as alamaridine(I1, m.p. 19s0, from the same source in 0.0001% yield.The structure elucidation and the biogenesis of the compound will be presented.

The alkaloid (−)-vincatine (I) has been synthesised by resolution of the intermediate acid III and its absolute stereochemistry suggested from CD data.

Bharatamine (I), mp 182–183°, a novel racemic protoberberine alkaloid unoxygenated at ring D and biogenetically derivable from loganin, a pathway hitherto unknown for this class of compounds, has been isolated from the seeds of Alanguim lamarckii and structure established by an unequivocal synthesis.