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J D McChesney

Publications and source records attributed to J D McChesney.

At least 19 recordsLinked to original sources
PubMed2001

Novel esters of glaucarubolone as inducers of terminal differentiation of promyelocytic HL-60 cells and inhibitors of 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesion formation in mouse mammary organ culture.

In an effort to discover new chemotherapeutic/chemopreventive agents from natural sources, brusatol (1) was found to induce HL-60 cellular differentiation, accompanied by strong antiproliferative and cytotoxic effects. A series of natural and semisynthetic quassinoids (1-48) was designed to effect both antiproliferative and differentiation-inducing properties. Compounds were assessed in vitro using the HL-60 promyelocytic cell model. Changes in activity due to structural modification of the core structure glaucarubolone (24) were consistent with activities reported in other cell systems. However, the following were novel SAR findings: (1) semisynthetic analogues with a hydroxylated ring at the beta-position of the ester side chain at C-15 were able to induce cellular differentiation at concentrations lower than those inducing cell growth arrest, and (2) quassinoids inhibiting DNA synthesis with greater efficacy than reducing cellular viability possessed alkyl substitutions at the alpha-position of the C-15 ester side chain. Analogues from this latter group and brusatol (1) and bruceantin (2) inhibited dimethylbenz(a)anthracene-induced preneoplastic lesion formation in a mouse mammary organ culture. The novel finding of 1 and glaucarubolone analogues as potent inducers of differentiation leads to potential novel applications in the field of cancer.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Transformation of jervine by Cunninghamella elegans ATCC 9245.

Preparative-scale fermentation of the known C-nor-D-homosteroidal jerveratrum alkaloid jervine with Cunninghamella elegans (ATCC 9245) has resulted in the isolation of (-)-jervinone as the major metabolite. In addition, C. elegans ATCC 9245 was able to epimerize C-3 of jervine, producing 3-epi-jervine. This epimerization reaction was similar to that reported for tomatidine, the known spirosolane-type Solanum alkaloid. The structure elucidation of both metabolites was based primarily on 1D- and 2D-NMR analyses.

Fermentation↗
PubMed1997

Antifungal activity of a new triterpenoid glycoside from Pithecellobium racemosum (M.).

PURPOSE: In a continuation of our search for novel antifungal compounds from higher plants, the standard extract of the bark of Pithecellobium racemosum was found to have good activity against important AIDS-related opportunistic yeasts. METHODS: The extract was subjected to bioguided fractionation using silica gel column chromatography which led to purification of triterpene glycosides. The structures of these compounds were determined by a combination of spectroscopic (IR, NMR, HRMS) and chemical methods. RESULTS: Compound 1 is a new glycoside, 3-O[alpha-L-arabinopyranosyl (1-2)][alpha-L arabinopyranosyl (1-6)]2-acetoamido-2-deoxy-beta-D-glucopyranosyl oleanolic acid and Compound 2 was identified as the known compound 3-O-[alpha-L-arabinopyranosyl (1-2)]alpha-L-arabinopyranosyl (1-6)] 2-acetamido-2-deoxy-beta-D-glucopyranosyl echinocystic acid. CONCLUSIONS: Compound 1 is a new glycoside, 3-O-[alpha-L-arabinopyranosyl (1-2)]alpha-L-arabinopyranosyl (1-6)]-2-acetoamido-2-deoxy-beta-D-glucopyranosyl oleanolic acid and exhibits moderate antifungal activity against T. mentogrophytes, C. albicans and S. cerevisiae with MIC values of 6.25, 12.5 and 12.5 micrograms/ml respectively.

Antifungal Agents↗
PubMed1997

Effect of drying conditions on the taxane content of the needles of ornamental Taxus.

The effect of drying intact clippings of Taxus on the recovery of taxol and related compounds was studied under different drying conditions which included tobacco drying barn, greenhouse, shadehouse, air conditioned laboratory, oven, and freeze-drying. For clippings dried under tobacco barn, greenhouse, oven, and freeze-drying conditions, nearly total recovery of the expected levels based upon projections from analysis of fresh biomass was observed for taxol and cephalomannine. However, only 75-80% of the expected values for 10-deacetyltaxol and 10-deacetylbaccatin III were found. When the length of drying was extended up to 10 and 15 days as in the shadehouse and laboratory conditions, the recovery of all taxanes was adversely affected.

Alkaloids↗
PubMed1997

Evaluation of four Narcissus cultivars as potential sources for galanthamine production.

Galanthamine, an alkaloid present in the Amaryllidaceae is currently undergoing clinical trials for the treatment of Alzheimer's. Common daffodils, Narcissus spp., contain galanthamine and other alkaloids. Four commercial Narcissus cultivars were evaluated as potential sources of galanthamine. Planting depths, planting densities, bulb size or flower bud removal did not affect galanthamine content.

Alzheimer Disease↗
PubMed1996

A new quassinoid from Castela texana.

A new quassinoid, 11-O-trans-p-coumaroyl amarolide (1) was isolated from Castela texana, and the structure was elucidated by spectroscopic analysis. Compound 1 is the first coumaroyl quassinoid derivative to have been isolated from nature. The known compounds amarolide (2), chaparrinone, chaparrin, glaucarubolone, holacanthone, and 15-O-beta-D-glucopyranosyl glaucarubol were also isolated. All isolated compounds were tested for their cytotoxicity and antiprotozoal activities.

Animals↗
PubMed1996

Intellectual property rights, naturally derived bioactive compounds, and resource conservation. Meeting report.

The first Interim Annual Meeting of the American Society of Pharmacognosy was held October 20-22, 1994, in San Jose, Costa Rica. In the symposium, which was the main scientific focus of the meeting, speakers from both developed and developing countries presented their perspectives on issues regarding intellectual property rights in regard to drug development from natural sources, conservation of natural habitats, and international conventions on bioprospecting. Careful evaluation of existing policies, laws, and conventions; sensitivity to the respective world views of prospective partners; equitable sharing of benefits including scientific collaboration; and a sense of fairness will be necessary to ensure that the genetic resources of all countries will be developed for the benefit of humankind.

Conservation of Natural Resources↗
PubMed1995

Pregnane glycosides from Stapelia variegata.

Eleven new pregnane ester glycosides have been isolated from the aerial parts of Stapelia variegata. Eight of the recognized compounds were established to possess the same trioside moiety, viz. 3-O-[3-O-methyl-6-deoxy-beta-D-allopyranosyl-(1-4)-beta-D- cymaropyranosyl-(1-4)-beta-D-cymaropyranoside]. These compounds were identified as: stavaroside A: 12-O-beta-angeloyl-20-O-benzoyl sarcostin; stavaroside B: 12-O-beta-angeloyl-20-O-tigloyl sarcostin; stavaroside C: 11 alpha-acetoxy 2 beta-benzoxy-3 beta,8 beta, 14 beta-trihydroxy-pregn-5-ene-20-one; stavaroside D: 11 alpha-acetoxy- 12 beta-tigloxy-3 beta,8 beta,14 beta-trihydroxy-pregn-5-ene-20-one; stavaroside E: 12-O-beta-benzoyl sarcostin; stavaroside F: 11 alpha-acetoxy-12 beta-acetoxy-3 beta,8 beta,14 beta-trihydroxy-pregn-5- ene-20-one; stavaroside G: 12-O-beta,20-O-diacetyl sarcostin and stavaroside H: 3 beta, 8 beta, 11 alpha, 12 beta, 14 beta-pentahydroxy-pregn-5- ene-20-one. The other three compounds were shown to possess the same tetraside sugar moiety, viz. 3-O-[beta-D-glucopyranosyl- (1-4)-3-O-methyl-6-deoxy-beta-D-allopyranosyl-(1-4)-beta-D-cymaropyra nosyl- (1-4)-beta-D-cymaropyranoside]. These compounds were identified as: stavaroside I: 1 alpha, 12 beta-angeloxy and benzoxy-3 beta,8 beta,14 beta-trihydroxy- pregn-5-ene-20-one; stavaroside J: 11 alpha-acetoxy-12 beta-benzoxy-3 beta, 8 beta,14 beta-trihydroxy-pregn-5-ene-20-one and stavaroside K: 11 alpha-acetoxy-12 beta-tigloxy-3 beta,8 beta,14 beta-trihydroxy-pregn-5-ene- 20-one. The structural elucidation of the isolated compounds was aided significantly on the basis of the chemical and spectral evidence. The decisive assignments of the ester positions were based on the Inverse Detected-Heteronuclear Multiple Bond Connectivity (HMBC) experiments.

Carbohydrate Sequence↗
PubMed1995

Microbial and mammalian metabolism studies on the semisynthetic antimalarial, deoxoartemisinin.

PURPOSE: Deoxoartemisinin is a semisynthetic antimalarial with potential for treatment of multiple drug resistant malaria. Metabolism studies were conducted to aid in future drug development. METHODS: Microbial model systems were employed which have been shown to be good predictors of mammalian drug metabolites. Metabolism studies using rats were also performed. RESULTS: Three microbial metabolites of deoxoartemisinin were identified (2, 3, and 4). Metabolite 3 was also found in rat plasma. HPLC/MS analyses were performed on the rat plasma using 2, 3, and 4 as standards. All metabolites were thoroughly characterized by 1H and 13C-NMR. An additional rat plasma metabolite was revealed and it was shown not to be 9 alpha-hydroxyartemisinin. CONCLUSIONS: Deoxoartemisinin was metabolized to three microbial metabolites. Metabolism by rats showed the presence of two metabolites in the plasma, one of which was the same as the microbial metabolite.

Animals↗
PubMed1995

Time course and inhibition of stavaroside K, veratramine and cevine-induced hemolysis by other pregnane glycosides and Veratrum alkaloids.

Stavaroside K, veratramine and cevine induce hemolysis, whereas 7 other pregnane stavarosides and 8 Veratrum alkaloids are not hemolytic. On the other hand, erythrocytes pretreated or incubated with low concentrations of stavarosides D-F or with the 8 other Veratrum alkaloids were resistant to hemolysis induced by authentic saponin, stavaroside K, cevine or veratramine. Veratridine, zygadenine and angeloylzygadenine (the known Na-Channel-Gate toxins) revealed the most potent reduction of hemolytic activity.

Cevanes↗
PubMed1994

Taxol content of stored fresh and dried Taxus clippings.

The taxol content of dried Taxus biomass was monitored monthly for 15 months. Intact and finely ground biomass was stored at room temperature (22 degrees-24 degrees) as well as under refrigeration (2 degrees-4 degrees). In addition, intact fresh clippings stored under refrigeration in sealed plastic bags for up to 10 weeks were evaluated for changes in taxol content. Analysis indicates that properly dried Taxus clippings can be stored either intact or powdered at room temperature or under refrigeration with no apparent loss of taxol content. The taxol content in fresh intact clippings was also stable for at least 10 weeks when stored under refrigeration.

Biomass↗
PubMed1993

A new antimalarial quassinoid from Simaba guianensis.

Two antimalarial quassinoids, gutolactone [1] and simalikalactone D [2], have been characterized by bioactivity-directed fractionation from the bark of Simaba guianensis collected near Manaus, Brazil. Compound 2 was previously isolated from Simaba multiflora and Quassia africana and shown to be an active antimalarial in vitro. This is the first occurrence of 1. The structure of the novel quassinoid was established by spectral methods including 2D nmr spectroscopy.

Animals↗
PubMed1993

Decomposition of arteether in simulated stomach acid yielding compounds retaining antimalarial activity.

In simulated stomach acid (aqueous 0.01 M HCl, 37 degrees C) beta-arteether decomposed (half-life, 441 +/- 17 min) to dihydroartemisinin, which subsequently rearranged to a new compound (1) having an endoperoxide group and an aldehyde group. The in vitro antimalarial activity of dihydroartemisinin is similar to that of beta-arteether, whereas compound 1 had approximately 1/10th the activity of beta-arteether. Compound 1 was prepared in sufficient quantities to afford samples for biological evaluation and a complete chemical characterization with 1H- and 13C-NMR and mass spectrometry. While beta-arteether would be somewhat unstable in the stomach, if the drug were administered on an empty stomach (emptying time, approximately 30 min) as a suspension or tablet, sufficient quantities of intact arteether may reach the small intestines, where it would be stable and readily absorbed. Its decomposition products, dihydroartemisinin and 1, may also contribute to the antimalarial activity of the administered drug following oral administration.

Animals↗
PubMed1993

Identification of four biliary metabolites of the diterpene sclareol in the laboratory rat.

1. Ag.l.c. method was developed to determine sclareol (1) and its microbial metabolites: 3-keto-sclareol (2), 2 alpha-hydroxysclareol (3), 3 alpha-hydroxysclareol (4), 3 beta-hydroxysclareol (5), 18-hydroxysclareol (6), and 2 alpha, 18-dihydroxysclareol (7) in both microbial cultures and biological fluids of the laboratory rat. 2. Metabolism of the diterpene (1) was studied in the laboratory rat. This in vivo study was facilitated by the availability of microbial metabolites of sclareol as reference standards, and the g.l.c. assay for sclareol and its metabolites in biological fluids. 3. Following i.v. treatment (100 mg/kg), the disappearance of (1) from rat plasma was rapid and biphasic. No microbial metabolites of sclareol were detectable in plasma. 4. Sclareol (1) and its microbial metabolites were not detected in rat urine following either i.v. or oral treatments; unchanged (1) was excreted in rat faeces to the extent of 9% of an oral dose in 48 h. 5. Following i.v. treatment, 0.02% dose was recovered in bile as unchanged (1). Four biliary metabolites of (1) (0.4% dose) were identified as (2), and (4)-(6) based on g.l.c.-mass spectrometry and comparisons with reference standards. All four biliary metabolites of (1) in rat have been identified as microbial metabolites of (1).

Animals↗
PubMed1992

Preparation of potential anti-inflammatory agents from dehydroabietic acid.

Methyl 16-nor-16-carboxydehydroabietate (22), 16-nor-16-carboxydehydroabietinol acetate (23), methyl 7-keto-16-nor-16-carboxydehydroabietate (29), 16-nor-16-carboxydehydroabietic acid (30), 16-nor-16-carboxydehydroabietinol (31), 7-keto-16-nor-16-carboxydehydroabietic acid (32), methyl 7-hydroxy-16-nor-16-carboxydehydroabietate (33), and 7-hydroxy-16-nor-16-carboxydehydroabietic acid (34) were prepared from dehydroabietic acid. Only 22 and 32 had weak anti-inflammatory activity.

Abietanes↗
PubMed1991

Identification of the in vivo metabolites of the antimalarial arteether by thermospray high-performance liquid chromatography/mass spectrometry.

The thermospray mass spectra of arteether and 16 of its potential metabolites all showed strong [M + NH4]+ ions and with only a few exceptions these compounds also showed spectral peaks corresponding to [M + NH4 - HOR]+ and [M + H - HOR]+, where OR represents the alkoxy or hydroxy group at the 12-position. A method for quantifying the metabolites was developed in which the plasma was spiked with an internal standard (the propyl ether analog of arteether), extracted using a C-18 solid-phase cartridge, then subjected to thermospray high-performance liquid chromatographic/mass spectrometric analysis using selected ion monitoring and a C-18 reversed-phase analytical column. Following the intravenous administration of arteether (11.6 mg kg-1), the plasma was found to contain 12 metabolites of arteether in the 10-1000 ng ml-1 range 15 min post-injection, and within 60 min two of these metabolites attained higher concentrations than that of the parent compound, while several other of the metabolites attained concentrations similar to the parent compound. The pseudo-first-order half-life of arteether was found to be 10.0 +/- 0.6 min, while the apparent half-lives of most of the metabolites were in the 15-30 min range. Nine of these metabolites were identified by comparison to authentic reference standards and the structures of three remaining metabolites were tentatively assigned from their spectral and chromatographic properties. The metabolic pathways leading to these 12 metabolites was a rather complex, multiple-step process, but most of the metabolites arose from an enzymatic oxidation at one of three sites; 3 alpha, 9 alpha, or the CH2 of the side-chain. Conversion of the endoperoxide group to an cyclic ether was not a major pathway. The in vitro antimalarial activity of reference standards of several of the metabolites was determined and all of those tested were found to be active in the low nanogram per milliliter range.

Animals↗