Cancer Drug Discovery and Development: New Paradigms for a New Millennium

Sausville, E. A.; Johnson, Jill; Cragg, Gordon M.; Decker, Shannon

doi:10.1021/bk-2001-0796.ch001

Cited by 3 publications

(6 citation statements)

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“…The results from National Cancer Institute (NCI)’s anti-HIV test showed both 22 and 29 were inactive to HIV. But surprisingly, compound 29 showed slight activity against certain human tumor cells in NCI’s 60 cell line screen 13,14. This intrigued us to think about its mechanism, and COMPARE30, 31 analysis with the NCI Standard Agent Database was performed.…”

Section: Resultsmentioning

confidence: 99%

“…Structure-activity relationship (SAR) data for the anthracenyl isoxazole amides synthesized ( 23–32 ) were acquired by evaluating their in vitro antitumor activity against NCI’s 60 human tumor cell lines 13,14,39,40. These cell lines have been derived from nine cancer types that adequately meet minimal quality assurance criteria representing leukemia, melanoma and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney.…”

Section: Resultsmentioning

confidence: 99%

“…We used 29 as a probe or seed compound in the NCI’s COMPARE Algorithm to rank the similarity of responses of the 60 cell lines to the standard agent database 13,14, 39, 40. Similarity of pattern to that of the seed is expressed quantitatively as a Pearson correlation coefficient (PCC).…”

Section: Resultsmentioning

confidence: 99%

“…While our initial foray into this arena met with encouraging anti-tumor activity in screens provided by the National Cancer Institute’s Developmental Therapeutics Program (NCI-DTP)13, 14 ( vide infra ), we will present evidence herein that our lead molecules did not appear to exert their bioactivity by binding B-DNA. Concurrent with our studies at this time, numerous workers recognized that non-B-DNA conformations are potentially feasible targets for anti-tumor drug development.…”

Section: Introductionmentioning

confidence: 98%

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Design, synthesis and biological evaluation of a novel class of anticancer agents: Anthracenylisoxazole lexitropsin conjugates

Han

Mosher

et al. 2009

Bioorganic & Medicinal Chemistry

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The synthesis and in vitro anti-tumor 60 cell lines screen of a novel series of anthracenyl isoxazole amides (AIMs)¥ (22-33) is described. The molecules consist of an isoxazole that pre-organizes a planar aromatic moiety and a simple amide and/or lexitropsin-oligopeptide. The new conjugate molecules were prepared via doubly activated amidation modification of Weinreb's amide formation technique, using SmCl 3 as an activating agent which produces improved yields for sterically hindered 3-aryl-4-isoxazolecarboxylic esters. The results of the National Cancer Institute's (NCI) 60 cell line screening assay show a distinct structure activity relationship (SAR), wherein a trend of the highest activity for molecules with one N-methylpyrrole peptide. Evidence consistent with a mechanism of action via the interaction of these compounds with G-quadruplex (G4) DNA, and a structural based rational for the observed selectivity of the AIMs for G4 over B-DNA is presented.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Design, synthesis and biological evaluation of a novel class of anticancer agents: Anthracenylisoxazole lexitropsin conjugates

Han

Mosher

et al. 2009

Bioorganic & Medicinal Chemistry

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“…The development of in vitro screening procedures as tools to identify chemopreventive foods or their chemopreventive fractions is important in identifying potentially beneficial foods or diets best suited for cancer prevention [7,8]. The measurement of antioxidant activity is an important screening method to compare the oxidation/reduction potentials of phytochemicals in various systems to predict in vivo activity.…”

Section: Introductionmentioning

confidence: 99%

Antitumor activity against murine lymphoma L5178Y model of proteins from cacao (Theobroma cacao L.) seeds in relation with in vitro antioxidant activity

Preza

Jaramillo

Puebla

et al. 2010

BMC Complement Altern Med

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BackgroundRecently, proteins and peptides have become an added value to foodstuffs due to new knowledge about its structural analyses as related to antioxidant and anticancer activity. Our goal was to evaluate if protein fractions from cacao seeds show antitumor activity on lymphoma murine L5178Y model. The antioxidant activity of these fractions was also evaluated with the aim of finding a correlation with the antitumor activity.MethodsDifferential extraction of proteins from unfermented and semi-fermented-dry cacao seeds was performed and characterized by SDS-PAGE and FPLC size-exclusion chromatography. Antitumor activity was evaluated against murine lymphoma L5178Y in BALB/c mice (6 × 104 cells i.p.), with a treatment oral dose of 25 mg/kg/day of each protein fraction, over a period of 15 days. Antioxidant activity was evaluated by the ABTS+ and ORAC-FL assays.ResultsAlbumin, globulin and glutelin fractions from both cacao seed type were obtained by differential solubility extraction. Glutelins were the predominant fraction. In the albumin fraction, polypeptides of 42.3 and 8.5 kDa were found in native conditions, presumably in the form of two peptide chains of 21.5 kDa each one. The globulin fraction presented polypeptides of 86 and 57 kDa in unfermented cacao seed that produced the specific-cacao aroma precursors, and after fermentation the polypeptides were of 45 and 39 kDa. The glutelin fraction presented proteins >200 kDa and globulins components <100 KDa in lesser proportion. Regarding the semifermented-dry cacao seed, it was observed that the albumin fraction showed antitumoral activity, since it caused significant decreases (p < 0.05) in the ascetic fluid volume and packed cell volume, inhibiting cell growth in 59.98 ± 13.6% at 60% of the population; while the greatest antioxidant capacity due to free radical scavenging capacity was showed by the albumin and glutelin fraction in both methods assayed.ConclusionThis study is the first report on the biological activity of semifermented-dry cacao protein fractions with their identification, supporting the traditional use of the plant. The albumin fraction showed antitumor and free radical scavenging capacity, however both activities were not correlated. The protein fractions could be considered as source of potential antitumor peptides.

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From oncogene to drug: development of small molecule tyrosine kinase inhibitors as anti-tumor and anti-angiogenic agents

Morin

2000

Oncogene

114

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Cancer Drug Discovery and Development: New Paradigms for a New Millennium

Cited by 3 publications

References 0 publications

Design, synthesis and biological evaluation of a novel class of anticancer agents: Anthracenylisoxazole lexitropsin conjugates

Design, synthesis and biological evaluation of a novel class of anticancer agents: Anthracenylisoxazole lexitropsin conjugates

Antitumor activity against murine lymphoma L5178Y model of proteins from cacao (Theobroma cacao L.) seeds in relation with in vitro antioxidant activity

From oncogene to drug: development of small molecule tyrosine kinase inhibitors as anti-tumor and anti-angiogenic agents

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