N1-Benzyl Tryptamine Pan-SHIP1/2 Inhibitors: Synthesis and Preliminary Biological Evaluation as Anti-Tumor Agents

Sandra Fernandes; Shea T. Meyer; Jigisha P. Shah; Arijit A. Adhikari; William G. Kerr; John D. Chisholm

doi:10.3390/molecules27238451

N1-Benzyl Tryptamine Pan-SHIP1/2 Inhibitors: Synthesis and Preliminary Biological Evaluation as Anti-Tumor Agents

Sandra Fernandes, Shea T. Meyer, Jigisha P. Shah, Arijit A. Adhikari, William G. Kerr, John D. Chisholm

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

2 Scopus citations

Abstract

Inhibition of phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP) with small molecule inhibitors leads to apoptosis in tumor cells. Inhibitors that target both SHIP1 and SHIP2 (pan-SHIP1/2 inhibitors) may have benefits in these areas since paralog compensation is not possible when both SHIP paralogs are being inhibited. A series of tryptamine-based pan-SHIP1/2 inhibitors have been synthesized and evaluated for their ability to inhibit the SHIP paralogs. The most active compounds were also evaluated for their effects on cancer cell lines.

Original language	English (US)
Article number	8451
Journal	Molecules
Volume	27
Issue number	23
DOIs	https://doi.org/10.3390/molecules27238451
State	Published - Dec 2022

Keywords

SHIP1
SHIP2
antitumor
medicinal chemistry
phosphatase
tryptamine

ASJC Scopus subject areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

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10.3390/molecules27238451

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title = "N1-Benzyl Tryptamine Pan-SHIP1/2 Inhibitors: Synthesis and Preliminary Biological Evaluation as Anti-Tumor Agents",

abstract = "Inhibition of phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP) with small molecule inhibitors leads to apoptosis in tumor cells. Inhibitors that target both SHIP1 and SHIP2 (pan-SHIP1/2 inhibitors) may have benefits in these areas since paralog compensation is not possible when both SHIP paralogs are being inhibited. A series of tryptamine-based pan-SHIP1/2 inhibitors have been synthesized and evaluated for their ability to inhibit the SHIP paralogs. The most active compounds were also evaluated for their effects on cancer cell lines.",

keywords = "SHIP1, SHIP2, antitumor, medicinal chemistry, phosphatase, tryptamine",

author = "Sandra Fernandes and Meyer, {Shea T.} and Shah, {Jigisha P.} and Adhikari, {Arijit A.} and Kerr, {William G.} and Chisholm, {John D.}",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = dec,

doi = "10.3390/molecules27238451",

language = "English (US)",

volume = "27",

journal = "Molecules",

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T1 - N1-Benzyl Tryptamine Pan-SHIP1/2 Inhibitors

T2 - Synthesis and Preliminary Biological Evaluation as Anti-Tumor Agents

AU - Fernandes, Sandra

AU - Meyer, Shea T.

AU - Shah, Jigisha P.

AU - Adhikari, Arijit A.

AU - Kerr, William G.

AU - Chisholm, John D.

PY - 2022/12

Y1 - 2022/12

N2 - Inhibition of phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP) with small molecule inhibitors leads to apoptosis in tumor cells. Inhibitors that target both SHIP1 and SHIP2 (pan-SHIP1/2 inhibitors) may have benefits in these areas since paralog compensation is not possible when both SHIP paralogs are being inhibited. A series of tryptamine-based pan-SHIP1/2 inhibitors have been synthesized and evaluated for their ability to inhibit the SHIP paralogs. The most active compounds were also evaluated for their effects on cancer cell lines.

AB - Inhibition of phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP) with small molecule inhibitors leads to apoptosis in tumor cells. Inhibitors that target both SHIP1 and SHIP2 (pan-SHIP1/2 inhibitors) may have benefits in these areas since paralog compensation is not possible when both SHIP paralogs are being inhibited. A series of tryptamine-based pan-SHIP1/2 inhibitors have been synthesized and evaluated for their ability to inhibit the SHIP paralogs. The most active compounds were also evaluated for their effects on cancer cell lines.

KW - SHIP1

KW - SHIP2

KW - antitumor

KW - medicinal chemistry

KW - phosphatase

KW - tryptamine

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U2 - 10.3390/molecules27238451

DO - 10.3390/molecules27238451

M3 - Article

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SN - 1420-3049

VL - 27

JO - Molecules

JF - Molecules

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ER -

N1-Benzyl Tryptamine Pan-SHIP1/2 Inhibitors: Synthesis and Preliminary Biological Evaluation as Anti-Tumor Agents

Abstract

Keywords

ASJC Scopus subject areas

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