Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents

Wen Cai; Mary Hassani; Rajesh Karki; Ervin D. Walter; Katherine H. Koelsch; Hassan Seradj; Jayana P. Lineswala; Hamid Mirzaei; Jeremy S. York; Fatemeh Olang; Minoo Sedighi; Jennifer S. Lucas; Thomas J. Eads; Anthony S. Rose; Sahba Charkhzarrin; Nicholas G. Hermann; Howard D. Beall; Mohammad Behforouz

doi:10.1016/j.bmc.2010.01.037

Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents

Wen Cai, Mary Hassani, Rajesh Karki, Ervin D. Walter, Katherine H. Koelsch, Hassan Seradj, Jayana P. Lineswala, Hamid Mirzaei, Jeremy S. York, Fatemeh Olang, Minoo Sedighi, Jennifer S. Lucas, Thomas J. Eads, Anthony S. Rose, Sahba Charkhzarrin, Nicholas G. Hermann, Howard D. Beall, Mohammad Behforouz

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

A series of lavendamycin analogues with two, three or four substituents at the C-6, C-7 N, C-2′, C-3′ and C-11′ positions were synthesized via short and efficient methods and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. The compounds were prepared through Pictet-Spengler condensation of the desired 2-formylquinoline-5,8-diones with the required tryptophans followed by further needed transformations. Metabolism and toxicity studies demonstrated that the best substrates for NQO1 were also the most selectively toxic to NQO1-rich tumor cells compared to NQO1-deficient tumor cells.

Original language	English (US)
Pages (from-to)	1899-1909
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	18
Issue number	5
DOIs	https://doi.org/10.1016/j.bmc.2010.01.037
State	Published - Mar 1 2010

Keywords

Antitumor
Cytotoxicity
Lavendamycin analogues
NQO1
Quinoline-5,8-diones

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2010.01.037

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Cai, W., Hassani, M., Karki, R., Walter, E. D., Koelsch, K. H., Seradj, H., Lineswala, J. P., Mirzaei, H., York, J. S., Olang, F., Sedighi, M., Lucas, J. S., Eads, T. J., Rose, A. S., Charkhzarrin, S., Hermann, N. G., Beall, H. D., & Behforouz, M. (2010). Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents. Bioorganic and Medicinal Chemistry, 18(5), 1899-1909. https://doi.org/10.1016/j.bmc.2010.01.037

Cai, W, Hassani, M, Karki, R, Walter, ED, Koelsch, KH, Seradj, H, Lineswala, JP, Mirzaei, H, York, JS, Olang, F, Sedighi, M, Lucas, JS, Eads, TJ, Rose, AS, Charkhzarrin, S, Hermann, NG, Beall, HD & Behforouz, M 2010, 'Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents', Bioorganic and Medicinal Chemistry, vol. 18, no. 5, pp. 1899-1909. https://doi.org/10.1016/j.bmc.2010.01.037

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title = "Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents",

abstract = "A series of lavendamycin analogues with two, three or four substituents at the C-6, C-7 N, C-2′, C-3′ and C-11′ positions were synthesized via short and efficient methods and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. The compounds were prepared through Pictet-Spengler condensation of the desired 2-formylquinoline-5,8-diones with the required tryptophans followed by further needed transformations. Metabolism and toxicity studies demonstrated that the best substrates for NQO1 were also the most selectively toxic to NQO1-rich tumor cells compared to NQO1-deficient tumor cells.",

keywords = "Antitumor, Cytotoxicity, Lavendamycin analogues, NQO1, Quinoline-5,8-diones",

author = "Wen Cai and Mary Hassani and Rajesh Karki and Walter, {Ervin D.} and Koelsch, {Katherine H.} and Hassan Seradj and Lineswala, {Jayana P.} and Hamid Mirzaei and York, {Jeremy S.} and Fatemeh Olang and Minoo Sedighi and Lucas, {Jennifer S.} and Eads, {Thomas J.} and Rose, {Anthony S.} and Sahba Charkhzarrin and Hermann, {Nicholas G.} and Beall, {Howard D.} and Mohammad Behforouz",

year = "2010",

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doi = "10.1016/j.bmc.2010.01.037",

language = "English (US)",

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AU - Cai, Wen

AU - Hassani, Mary

AU - Karki, Rajesh

AU - Walter, Ervin D.

AU - Koelsch, Katherine H.

AU - Seradj, Hassan

AU - Lineswala, Jayana P.

AU - Mirzaei, Hamid

AU - York, Jeremy S.

AU - Olang, Fatemeh

AU - Sedighi, Minoo

AU - Lucas, Jennifer S.

AU - Eads, Thomas J.

AU - Rose, Anthony S.

AU - Charkhzarrin, Sahba

AU - Hermann, Nicholas G.

AU - Beall, Howard D.

AU - Behforouz, Mohammad

PY - 2010/3/1

Y1 - 2010/3/1

N2 - A series of lavendamycin analogues with two, three or four substituents at the C-6, C-7 N, C-2′, C-3′ and C-11′ positions were synthesized via short and efficient methods and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. The compounds were prepared through Pictet-Spengler condensation of the desired 2-formylquinoline-5,8-diones with the required tryptophans followed by further needed transformations. Metabolism and toxicity studies demonstrated that the best substrates for NQO1 were also the most selectively toxic to NQO1-rich tumor cells compared to NQO1-deficient tumor cells.

AB - A series of lavendamycin analogues with two, three or four substituents at the C-6, C-7 N, C-2′, C-3′ and C-11′ positions were synthesized via short and efficient methods and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. The compounds were prepared through Pictet-Spengler condensation of the desired 2-formylquinoline-5,8-diones with the required tryptophans followed by further needed transformations. Metabolism and toxicity studies demonstrated that the best substrates for NQO1 were also the most selectively toxic to NQO1-rich tumor cells compared to NQO1-deficient tumor cells.

KW - Antitumor

KW - Cytotoxicity

KW - Lavendamycin analogues

KW - NQO1

KW - Quinoline-5,8-diones

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Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents

Abstract

Keywords

ASJC Scopus subject areas

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