Synthesis, in vitro and in vivo cytotoxicity of 6,7-diaryl-2,3,8,8a-tetrahydroindolizin-5(1H)-ones

F. Scott Kimball; Ashok Rao Tunoori; Samuel F. Victory; Dinah Dutta; Jonathan M. White; Richard H. Himes; Gunda I. Georg

doi:10.1016/j.bmcl.2007.05.103

Synthesis, in vitro and in vivo cytotoxicity of 6,7-diaryl-2,3,8,8a-tetrahydroindolizin-5(1H)-ones

F. Scott Kimball, Ashok Rao Tunoori, Samuel F. Victory, Dinah Dutta, Jonathan M. White, Richard H. Himes, Gunda I. Georg

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

19 Scopus citations

Abstract

A 6,7-diaryl-2,3,8,8a-tetrahydroindolizin-5(1H)-one library was constructed and tested against the colon cancer cell line HCT-116 as an initial screen for cytotoxic properties. Of this library, the parent compound, in which the southern aromatic ring remains unsubstituted, and the northern aromatic ring carries a 4-methoxy group, exhibited the most potent cytotoxicity with an IC₅₀ value of 0.39 μM and displayed promising activity in vivo in the NCI's mouse hollow fiber assay.

Original language	English (US)
Pages (from-to)	4703-4707
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	16
DOIs	https://doi.org/10.1016/j.bmcl.2007.05.103
State	Published - Aug 15 2007
Externally published	Yes

Bibliographical note

Funding Information:
These studies were supported by the National Cancer Institute (CA 90602 and N01-CM-67259). The authors thank Dr. Ravi Varma (NCI, DTP) for carrying out the COMPARE analysis for analog 12 (NSC 707904) and for his support of this project. We also wish to thank the NCI’s DTP for carrying out cytotoxicity assays for compounds 12 (NSC 707904), 14 (NSC 707907), and 27 (NSC 707909). The complete cancer screening data for these compounds are available on the DTP website.

Keywords

COMPARE analysis
Colon cancer
HCT-116
NCI mouse hollow fiber assay
Seco-phenanthroindolizidine alkaloids

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Synthesis, in vitro and in vivo cytotoxicity of 6,7-diaryl-2,3,8,8a-tetrahydroindolizin-5(1H)-ones",

abstract = "A 6,7-diaryl-2,3,8,8a-tetrahydroindolizin-5(1H)-one library was constructed and tested against the colon cancer cell line HCT-116 as an initial screen for cytotoxic properties. Of this library, the parent compound, in which the southern aromatic ring remains unsubstituted, and the northern aromatic ring carries a 4-methoxy group, exhibited the most potent cytotoxicity with an IC50 value of 0.39 μM and displayed promising activity in vivo in the NCI's mouse hollow fiber assay.",

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note = "Funding Information: These studies were supported by the National Cancer Institute (CA 90602 and N01-CM-67259). The authors thank Dr. Ravi Varma (NCI, DTP) for carrying out the COMPARE analysis for analog 12 (NSC 707904) and for his support of this project. We also wish to thank the NCI{\textquoteright}s DTP for carrying out cytotoxicity assays for compounds 12 (NSC 707904), 14 (NSC 707907), and 27 (NSC 707909). The complete cancer screening data for these compounds are available on the DTP website.",

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AU - Tunoori, Ashok Rao

AU - Victory, Samuel F.

AU - Dutta, Dinah

AU - White, Jonathan M.

AU - Himes, Richard H.

AU - Georg, Gunda I.

N1 - Funding Information: These studies were supported by the National Cancer Institute (CA 90602 and N01-CM-67259). The authors thank Dr. Ravi Varma (NCI, DTP) for carrying out the COMPARE analysis for analog 12 (NSC 707904) and for his support of this project. We also wish to thank the NCI’s DTP for carrying out cytotoxicity assays for compounds 12 (NSC 707904), 14 (NSC 707907), and 27 (NSC 707909). The complete cancer screening data for these compounds are available on the DTP website.

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N2 - A 6,7-diaryl-2,3,8,8a-tetrahydroindolizin-5(1H)-one library was constructed and tested against the colon cancer cell line HCT-116 as an initial screen for cytotoxic properties. Of this library, the parent compound, in which the southern aromatic ring remains unsubstituted, and the northern aromatic ring carries a 4-methoxy group, exhibited the most potent cytotoxicity with an IC50 value of 0.39 μM and displayed promising activity in vivo in the NCI's mouse hollow fiber assay.

AB - A 6,7-diaryl-2,3,8,8a-tetrahydroindolizin-5(1H)-one library was constructed and tested against the colon cancer cell line HCT-116 as an initial screen for cytotoxic properties. Of this library, the parent compound, in which the southern aromatic ring remains unsubstituted, and the northern aromatic ring carries a 4-methoxy group, exhibited the most potent cytotoxicity with an IC50 value of 0.39 μM and displayed promising activity in vivo in the NCI's mouse hollow fiber assay.

KW - COMPARE analysis

KW - Colon cancer

KW - HCT-116

KW - NCI mouse hollow fiber assay

KW - Seco-phenanthroindolizidine alkaloids

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Synthesis, in vitro and in vivo cytotoxicity of 6,7-diaryl-2,3,8,8a-tetrahydroindolizin-5(1H)-ones

Abstract

Bibliographical note

Keywords

UN SDGs

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