PubMed Health⌕ Search

Biomedical subjects

G M Cragg

Publications and source records attributed to G M Cragg.

At least 37 records · Page 2Linked to original sources
PubMed1993

Two new cytotoxic chalcones from Calythropsis aurea.

The crude extract of Calythropsis aurea (Myrtaceae) produced a pattern of differential cytotoxicity in the NCI 60 cell line assay which was similar to those of known tubulin-interactive compounds. Cytotoxicity-guided fractionation led to the isolation of two new chalcones, calythropsin [1] and dihydrocalythropsin [2], which were responsible for the activity. Calythropsin was demonstrated to have a weak effect on mitosis, and presumably also on tubulin polymerization.

Animals↗
PubMed1992

The calanolides, a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophyllum lanigerum.

Eight new coumarin compounds (1-8) were isolated by anti-HIV bioassay-guided fractionation of an extract of Calophyllum lanigerum. The structures of calanolide A (1), 12-acetoxycalanolide A (2), 12-methoxycalanolide A (3), calanolide B (4), 12-methoxycalanolide B (5), calanolide C (6) and related derivatives 7 and 8 were solved by extensive spectroscopic analyses, particularly HMQC, HMBC, and difference NOE NMR experiments. The absolute stereochemistry of calanolide A (1) and calanolide B (4) was established by a modified Mosher's method. Calanolides A (1) and B (4) were completely protective against HIV-1 replication and cytopathicity (EC50 values of 0.1 microM and 0.4 microM, respectively), but were inactive against HIV-2. Some of the related compounds also showed evidence of anti-HIV-1 activity. Studies with purified bacterial recombinant reverse transcriptases (RT) revealed that the calanolides are HIV-1 specific RT inhibitors. Moreover, calanolide A was active not only against the AZT-resistant G-9106 strain of HIV-1 but also against the pyridinone-resistant A17 strain. This was of particular interest since the A17 virus is highly resistant to previously known HIV-1 specific, non-nucleoside RT inhibitors (e.g., TIBO; BI-RG-587; L693,593) which comprise a structurally diverse but apparently common pharmacologic class. The calanolides represent a substantial departure from the known class and therefore provide a novel new anti-HIV chemotype for drug development.

Antiviral Agents↗
PubMed1992

Anti-HIV and cytotoxic alkaloids from Buchenavia capitata.

The anti-HIV activity in the organic solvent extract of leaves of Buchenavia capitata was traced to a series of known flavonoid alkaloids, which represent a new chemotype for anti-HIV activity. The 13C-nmr assignments for this series of compounds have been revised. O-Demethylbuchenavianine [1] was the most active compound of the series but produced only moderate cytoprotective effects against HIV in cultured human lymphoblastoid (CEM-SS) cells. Compound 1 was cytotoxic also in the NCI human disease-oriented in vitro tumor screening panel and produced a pattern of modest differential cellular sensitivity.

Alkaloids↗
PubMed1992

Cytotoxic quassinoids from Cedronia granatensis.

The NCI in vitro primary disease-oriented antitumor screen has been used to select and guide the fractionation of the organic and aqueous extracts of Cedronia granatensis. Two quassinoids, sergiolide [1] and isobrucein B [2], to which the screening panel cell lines exhibited up to a 1000-fold range of differential sensitivity, were isolated. At concentrations of 10(-5)-10(-8) M, the compounds typically produced LC50-level responses against a majority of the melanoma lines and several of the colon, lung, and other solid tumor lines. These and related quassinoids may, therefore, be of interest for in vivo evaluation in appropriate xenograft tumor models.

Antineoplastic Agents, Phytogenic↗
PubMed1987

Solution-phase secondary-ion mass spectrometry of protonated amino acids.

Although sulfolane proved unexpectedly to be a poor solvent for solution-phase secondary-ion mass spectrometry of underivatized amino acids in the presence of thallium(I) salts, glycerol was somewhat more effective. Also, the addition of trifluoromethanesulfonic acid proved more effective than addition of the metal in generating molecular ion complexes. A convenient and reliable method for rapidly determining amino acid molecular ions is based on these observations.

Amino Acids↗
PubMedDate not supplied

Antineoplastic agents, 88. Pimelea prostrata.

The aerial portion of Pimelea prostrata (Thymelaeaceae) collected in New Zealand was evaluated as a source of substances that inhibit growth of the murine P-388 lymphocytic leukemia (PS). Simplexin (1) and Pimelea factor P2 (2) were found to strongly inhibit growth (ED50 5 X 10(-3) and 8 X 10(-4) micrograms/ml, respectively) of the PS in vitro cell line. The cyclic orthoester (2) was also found to inhibit growth (T/C 132 at 20 micrograms/kg) of the PS in vivo system. Detailed 1H-nmr (at 400 MHz) and 13C-nmr studies combined with fast atom bombardment mass spectral evidence were employed to confirm the structural assignments.

Animals↗
PubMedDate not supplied

Antineoplastic agents, 99. Amaryllis belladonna.

Amaryllis belladonna bulbs were examined for constituents inhibitory against the murine P-388 lymphocytic leukemia (PS system). Two in vitro active alkaloids, acetylcaranine (2; 9PS ED50 0.23 microgram/ml) and ambelline (3; 9PS ED50 1.6 micrograms/ml), were isolated accompanied by undulatine. However, the non-chiral anhydrolycorinium chloride (5) was found to be the principal antineoplastic (3 PS, 64-69% life extension at dose levels 10 to 20 mg/kg in vivo, ED50 1.4 micrograms/ml in vitro) component. Quaternary chloride 5 has not been located previously among plant or animal biosynthetic products.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Antineoplastic agents, 103. The isolation and structure of hypoestestatins 1 and 2 from the East African Hypoëstes verticillaris.

The East African shrub Hypoëstes verticillaris representing a heretofore chemically unexplored. Acanthaceae genus has been found to contain two new cell growth inhibitory (murine P-388 lymphocytic leukemia) phenanthroindolizidine alkaloids termed hypoestestatin 1 (1a) and hypoestestatin 2 (1b). Both substances were found to markedly inhibit growth of the murine P-388 cell line (ED50 = 10(-5) micrograms/ml). The structures of hypoestestatins 1 and 2 were assigned primarily on the basis of results from extensive spectral studies.

Alkaloids↗
PubMedDate not supplied

Antineoplastic agents, 120. Pancratium littorale.

The bulbs of Pancratium littorale collected in Hawaii were found to contain a new phenanthridone biosynthetic product designated pancratistatin (4a) that proved to be effective (38-106% life extension at 0.75-12.5 mg/kg dose levels) against the murine P-388 lymphocytic leukemia. Pancratistatin also markedly inhibited (ED50, 0.01 microgram/ml) growth of the P-388 in vitro cell line and in vivo murine M-5076 ovary sarcoma (53-84% life extension at 0.38-3.0 mg/kg). An X-ray crystal structure determination of pancratistatin monomethyl ether (4c) and a detailed high resolution (400 MHz) nmr study of pancratistatin and its pentaacetate (4b) completed assignment of structure 4a. Companion antineoplastic constituents of P. littorale were found to be narciclasine (2c) and its 7-deoxy derivative (2a). The structure of 7-deoxynarciclasine (2c) was also confirmed by an X-ray crystallographic analysis.

Amaryllidaceae Alkaloids↗
PubMedDate not supplied

Antineoplastic agents, 122. Constituents of Combretum caffrum.

An investigation of the South African tree Combretum caffrum (Combretaceae) for antineoplastic constituents was conducted by employing the astrocytoma bioassay (9ASK). By this approach and a combination of solvent partition, steric exclusion, and adsorption chromatographic procedures, a substance designated combretastatin [1a] was isolated and found to display significant (71-90% astrocyte reversal at 1-100 micrograms/ml dose levels) astrocyte reversal and murine P-388 lymphocytic leukemia (PS) cell growth inhibition (ED50 0.011 micrograms/ml). The structure of (-)-combretastatin was elucidated by X-ray crystal structure analysis and confirmed by total synthesis. The absolute configuration at C-10 was assigned the R-configuration on the basis of Horeau esterification techniques. Other prominent, albeit PS-inactive, constituents were found to be 3,3',4'-tri-O-methylellagic acid [2] and acacetin [3].

Animals↗