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Biomedical subjects

J L McLaughlin

Publications and source records attributed to J L McLaughlin.

At least 55 records · Page 3Linked to original sources
PubMed1997

Konishiol, a new sesquiterpene, and bioactive components from Cunninghamia konishii.

Three sesquiterpenes, konishiol (1), cadalenol (2), 3-cedranol (3), one diterpene, manool (4), and one lignan, (+)-tsugacetal (5), have been isolated, for the first time, from the whole plant of Cunninghamia konishii by using bioactivity-directed fractionation. Compound 1 is new to the literature, and its chemical structure was determined by various spectroscopic analyses including EIMS, HREIMS, NOE, NOESY, and by preparing its di-acetyl derivative (1a). Compounds 2-5 showed moderate to weak bioactivities in brine shrimp (BST) and mosquito larvae (YFM) bioassays as well as cytotoxicities against three human solid tumor cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Bioactive furonaphtoquinones from Tabebuia barbata (Bignoniaceae).

Tabebuia barbata (E. Mey) Sandw. (Bignoniaceae), locally known as "palo de arco", is indigenous to the upper Orinoco and Amazonas rivers. Brine shrimp lethality-directed fractionation and extensive column chromatography, normal-phase preparative TLC and normal-phase HPLC separation of the ethanol extract of the bark of this previously uninvestigated species has led to the isolation of five active compounds 1-5. The combined spectral evidence (UV, IR, 1H and 13C NMR and mass) identified these compounds as naphthoquinones. These compounds, characterized as lapachol (1), 2-acetylnaphtho-[2,3-b]-furan-4,9-dione (2), 2-acetyl-5-hydroxy-naphtho-[2,3-b]-furan-4,9-dione (3), 2-acetyl-8-hydroxy-naphtho-[2,3-b]-furan-4,9-dione (4), and (+)-8-hydroxy-2(1-hydroxy-ethyl) naphtho-[2,3-b]-furan-4,9-dione (5), were reported previously from other species of the genus Tabebuia but not from T. barbata. Compounds 2-5, reference adriamycin, were significantly cytotoxic against A-549 human lung adeno-carcinoma, MCF-7 human breast carcinoma, and HT-29 human colon carcinoma cells. The compounds isolated (1-5) were also shown to be inhibitors of electron transport in rat liver mitochondria, reference to rotenone, with IC50 values in the range of 15 microM to 82.5 microM. In addition, this study demonstrated that screening and activity-directed fractionation, using brine shrimp lethality as a simple and inexpensive bioassay, can effectively lead to potential antitumor compounds.

Animals↗
PubMed1996

Longimicins A-D: novel bioactive acetogenins from Asimina longifolia (annonaceae) and structure-activity relationships of asimicin type of annonaceous acetogenins.

Bioactivity-directed fractionation of the ethanol extract of Asimina longifolia led to the isolation of four novel bioactive annonaceous acetogenins: longimicins A-D (1-4). Compounds 1-4 represent the asimicin type of acetogenins; however, the locations of the adjacent bis-tetrahydrofuran (THF) ring moieties are shifted along the aliphatic chains compared to the known compounds of this type. They are the first examples among this type of acetogenins with the placements of the ring systems altered. Compounds 1-4 showed bioactivities in several bioassays, but they are less active than their structural isomers. Study of their structure-activity relationships (SAR) reveals that the position of the adjacent bis-THF ring moiety is essential for maximization of the bioactivities among these asimicin type annonaceous acetogenins.

Animals↗
PubMed1996

Selectively cytotoxic diterpenes from Euphorbia poisonii.

Bioactivity-guided fractionation of the latex of Euphorbia poisonii Pax. (Euphorbiaceae) led to the isolation and characterization of a new tigliane diterpene, 12-deoxyphorbol 13-(9,10-methylene)undecanoate (3), together with five known diterpenes (1,2,4-6). When evaluated for cytotoxicity in a panel of six human solid tumor cell lines, the diterpene esters, 1-3, 5, and 6, were selectively cytotoxic for the human kidney carcinoma (A-498) cell line with potencies for 2 and 3 exceeding that of adriamycin by ten thousand times. Details of the isolations, structural analyses, and cytotoxic activities are described.

Adenocarcinoma↗
PubMed1996

(2,4-cis)-asimicinone and (2,4-trans)-asimicinone: two novel bioactive ketolactone acetogenins from Asimina triloba (Annonaceae).

Two novel bioactive ketolactone Annonaceous acetogenins, (2,4-cis)-asimicinone (1) and (2,4-trans)-asimicinone (2), have been isolated from Asimina triloba (Annonaceae) by bioactivity directed fractionation. The separation of these two epimeric compounds was achieved by HPLC methods using a Si gel normal phase column eluted with acetone in hexane gradients. The assignments of cis or trans stereochemistry of the ketolactone moieties were made on the bases of 1H-1H COSY and NOESY experiments. 1 and 2 showed selective cytotoxicities against A-549 (human lung cancer) and MCF-7 (human breast cancer) cell lines with ED50 values as low as < 10(-7) micrograms/ml with 2 being the more active isomer.

Acetylation↗
PubMed1996

SARs of annonaceous acetogenins in rat liver mitochondria.

The Annonaceous acetogenins represent a class of compounds with diverse bioactivities, including promising cytotoxicites. These are due, at least in part, to inhibition of complex I in the oxidative phosphorylation pathway in mitochondria. Fourteen Annonaceous acetogenins were tested in a rat liver mitochondrial oxygen uptake assay to probe additional structure-activity relationships. In this subcellular assay, the activity of non-adjacent bis-THF ring acetogenins depends on the distance between the two THF rings; the activity decreases to that of a mono-THF ring acetogenin if the distance is too long. When one THF ring is replaced with a tetrahydropyran ring, the activity remains comparable. The configuration of the THF ring, in mono ring compounds, seems to be more important than stereochemical differences in the rings of adjacent bis-THF ring compounds. Bullatacin, an adjacent bis-THF ring acetogenin, was used as a standard compound in every run to normalize the data.

Animals↗
PubMed1996

The absolute configuration of adjacent bis-THF acetogenins and asiminocin, a novel highly potent asimicin isomer from Asimina triloba.

A novel acetogenin, asiminocin (1), was isolated by activity-directed fractionation from the stem bark of the paw paw tree, Asimina triloba. By spectral and chemical methods, 1 was identified as (30S)-hydroxy-4-deoxyasimicin. The absolute configuration of 1, along with those of previously reported acetogenins asimin, asiminacin, bullatin, (30S)-bullanin, and (30R) bullanin, was determined by Mosher ester methodology. Compound 1 was highly inhibitory to three human solid tumor cell lines with over a billion times the potency of adriamycin.

Animals↗
PubMed1996

Longifolicin, longicoricin, and gigantetroneninone, three novel bioactive mono-tetrahydrofuran annonaceous acetogenins from Asimina longifolia (Annonaceae).

Longifolicin (1), longicoricin (2) and (2,4-cis and trans)-gigantetroneninone (3), three novel bioactive mono-tetra-hydrofuran (THF) gamma-lactone acetogenins, were isolated from the leaves and twigs of Asimina longifolia (Annonaceae) by directing the fractionation with the brine shrimp lethality test (BST). The structures were elucidated based on spectroscopic and chemical methods. Compounds 1-3 showed selective and potent cytotoxicities to certain human tumor cell lines.

Animals↗
PubMed1996

cis-gigantrionenin and 4-acetyl gigantetrocin A, two new bioactive annonaceous acetogenins from Goniothalamus giganteus, and the stereochemistries of acetogenin 1,2,5-triols.

Using activity-directed fractionation, two new bioactive acetogenins, cis-gigantrionenin (1) and 4-acetyl gigantetrocin A (2), have been isolated from the bark of Goniothalamus giganteus (Annonaceae). Compound 1 has a cis-mono-THF ring with one flanking hydroxyl and possesses a cis-double bond at C-21/22 of the aliphatic chain; it represents only the second example of the cis-mono-THF ring annonaceous acetogenins having one flanking hydroxyl. Compound 2 has a trans-mono-THF ring with one flanking hydroxyl, but it possesses a mono-acetyl group at the 4-OH position; it represents only the second natural example of the acetylated annonaceous acetogenins; the first acetogenin reported, uvaricin, was mono-acetylated at the 24-OH. The stereochemistries of 1 and 2 were determined by the advanced Mosher ester method. In addition, the absolute stereochemistries of gigantriocin (3), gigantrionenin (4), and giganenin (5) were determined by the advanced Mosher ester method and by circular dichroism (CD). The stereochemistries of the 7,8-diols in murihexocins A (6) and B (7) were determined to have the S,S-configurations, respectively.

Animals↗
PubMed1996

Applying Mosher's method to acetogenins bearing vicinal diols. The absolute configurations of muricatetrocin C and rollidecins A and B, new bioactive acetogenins from Rollinia mucosa.

Muricatetrocin C (1), rollidecin A (2), and rollidecin B (3), three new bioactive annonaceous acetogenins bearing vicinal diols, were isolated from the leaves of Rollinia mucosa (Annonaceae) using activity-directed fractionation. The total structural elucidations of 1-3, including the absolute stereochemistries of the vicinal diols, were achieved by analyzing their per-Mosher ester derivatives. All three compounds showed potent and selective inhibitory effects against several human cancer cell lines.

4-Butyrolactone↗
PubMed1996

New 19-acetoxyingol diterpenes from the latex of Euphorbia poisonii (Euphorbiaceae).

The poisonous latex of Euphorbia poisonii gave bioactive 3,12-diacetyl-8-nicotinyl-7-phenylacetyl 19-acetoxyingol (1) together with its less active congeners, 3,12-diacetyl-7-phenylacetyl 19-acetoxyingol (2) and 3-acetyl-7-phenylacetyl 19-acetoxyingol (3). The chemical structures of 1-3 were determined by spectroscopic methods including HRMS, DEPT, HETCOR, COSY, NOESY, HMQC and HMBC. The absolute configurations of the hydroxylated carbons in 2 and 3 were provisionally suggested by the Mosher ester method. Bioactivity-guided isolation, structure determination and cytotoxic activity of the new ingols are described.

Animals↗
PubMed1996

Five novel mono-tetrahydrofuran ring acetogenins from the seeds of Annona muricata.

Bioactivity-directed fractionation of the seeds of Annona muricata L. (Annonaceae) resulted in the isolation of five new compounds: cis-annonacin (1), cis-annonacin-10-one (2), cis-goniothalamicin (3), arianacin (4), and javoricin (5). Three of these (1-3) are among the first cis mono-tetrahydrofuran ring acetogenins to be reported. NMR analyses of published model synthetic compounds, prepared cyclized formal acetals, and prepared Mosher ester derivatives permitted the determinations of absolute stereochemistries. Bioassays of the pure compounds, in the brine shrimp test, for the inhibition of crown gall tumors, and in a panel of human solid tumor cell lines for cytotoxicity, evaluated relative potencies. Compound 1 was selectively cytotoxic to colon adenocarcinoma cells (HT-29) in which it was 10,000 times the potency of adriamycin.

4-Butyrolactone↗
PubMed1996

Squamotacin: an annonaceous acetogenin with cytotoxic selectivity for the human prostate tumor cell line (PC-3).

The bark extracts of Annona squamosa yielded a new bioactive acetogenin, squamotacin (1), and the known compound, molvizarin (2), which is new to this species. Compound 1 is identical to the potent acetogenin, bullatacin (3), except that the adjacent bistetrahydrofuran (THF) rings and their flanking hydroxyls are shifted two carbons toward the gamma-lactone ring. Compound 1 showed cytotoxic selectively for the human prostate tumor cell line (PC-3), with a potency of over 100 million times that of Adriamycin.

4-Butyrolactone↗
PubMed1996

Rollinecins A and B: two new bioactive annonaceous acetogenins from Rollinia mucosa.

Two new mono-THF ring acetogenins, rollinecins A (1) and B (2), were isolated from the partitioned ethanolic extracts of the leaves of Rollinia mucosa (Annonaceae) by activity-directed fractionation. 1 and 2 are epimeric at the C-14 carbinol stereocenter. Their absolute stereochemical structures were solved by preparing their respective per-Mosher ester derivatives. 1 and 2 showed equivalent and selective in vitro activities against several human solid tumor cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Bioactive ent-kaurene diterpenoids from Annona senegalensis.

Activity-guided fractionation of the stem bark of Annona senegalensis gave four bioactive ent-kaurenoids (1-4). Compound 2 showed selective and significant cytotoxicity for MCF-7 (breast cancer) cells (ED50 1.0 microgram/mL), and 3 and 4 exhibited cytotoxic selectivity for PC-3 (prostate cancer) cells but with weaker potencies (ED50 17-18 micrograms/mL). The structure of the new compound, 3, was deduced from spectral evidence.

Africa↗
PubMed1996

Five new monotetrahydrofuran ring acetogenins from the leaves of Annona muricata.

Bioactivity-directed fractionation of the leaves of Annona muricata resulted in the isolation of annopentocins A (1), B (2), and C(3), and cis- and trans-annomuricin-D-ones (4, 5). Compounds 1-3 are the first acetogenins reported bearing a mono-tetrahydrofuran (THF) ring with one flanking hydroxyl, on the hydrocarbon side, and another hydroxyl, on the lactone side, that is one carbon away from the THF ring. Compounds 4 and 5 were obtained in a mixture and are new mono-THF ring acetogenins bearing two flanking hydroxyls and an erythro-diol located between the THF and the ketolactone rings. Compound 1 was selectively cytotoxic to pancreatic carcinoma cells (PACA-2), and 2 and 3 were selectively cytotoxic to lung carcinoma cells (A-549); the mixture of 4 and 5 was selectively cytotoxic for the lung (A-549), colon (HT-29), and pancreatic (PACA-2) cell lines with potencies equal to or exceeding those of Adriamycin.

4-Butyrolactone↗
PubMed1996

Chlorinated annonaceous acetogenins and their bioactivities.

4(S)-Chloro-4-deoxygigantetrocin A and 4(S), 18-dichloro-4,18-dideoxyasimilobin were obtained by treating gigantetrocin A with triphenylphosphine and CCl4. The structures were determined by spectroscopic methods. The chlorinated compounds show decreased bioactivities in the brine shrimp lethality test and against human tumor cell lines.

4-Butyrolactone↗