Fluorescent phosphoinositide 3-kinase inhibitors suitable for monitoring of intracellular distribution

Donghee Kim; Hyunseung Lee; Hwiseok Jun; Soon Sun Hong; Sungwoo Hong

doi:10.1016/j.bmc.2011.03.025

Fluorescent phosphoinositide 3-kinase inhibitors suitable for monitoring of intracellular distribution

Donghee Kim, Hyunseung Lee, Hwiseok Jun, Soon Sun Hong, Sungwoo Hong

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

15 Scopus citations

Abstract

The monitoring of the drug behavior and distribution in biological system can provide information whether drug reaches its desired target, and a biological rationale for the design of new therapeutics. We have developed a family of potent fluorescent PI3Kα inhibitors in which part of the fluorophore was engineered to be a pharmacophore capable of inhibiting PI3Kα. These xanthine derivatives are characterized by a donor-acceptor molecular structure, and changes in the electronic properties of the two variation points at R₁ and R₂ give rise to notable bathochromic shifts in the λ_{em, abs} and increase the value of Φ_F. Further, we illustrated the use of E2 (PI3Kα/IC ₅₀ = 0.068 μM, T47D cell viability: IC₅₀ = 0.9 μM) to block cancer cell proliferation and to monitor its subcellular localization by fluorescence microscopy.

Original language	English
Pages (from-to)	2508-2516
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	19
Issue number	8
DOIs	https://doi.org/10.1016/j.bmc.2011.03.025
State	Published - 15 Apr 2011
Externally published	Yes

Bibliographical note

Funding Information:
This research was supported by National Research Foundation of Korea (NRF) through general research grants (NRF-2010-0015340 and 2010-0022179), by the Korean Health Technology R&D Project (A101185), and by the National R&D Program for Cancer Control (1020250), Ministry for Health, Welfare and Family Affairs, Korea.

Keywords

Anticancer
Drug design
Fluorescent PI3K inhibitor
Intracellular distribution

UN SDGs

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

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10.1016/j.bmc.2011.03.025

Cite this

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title = "Fluorescent phosphoinositide 3-kinase inhibitors suitable for monitoring of intracellular distribution",

abstract = "The monitoring of the drug behavior and distribution in biological system can provide information whether drug reaches its desired target, and a biological rationale for the design of new therapeutics. We have developed a family of potent fluorescent PI3Kα inhibitors in which part of the fluorophore was engineered to be a pharmacophore capable of inhibiting PI3Kα. These xanthine derivatives are characterized by a donor-acceptor molecular structure, and changes in the electronic properties of the two variation points at R1 and R2 give rise to notable bathochromic shifts in the λem, abs and increase the value of ΦF. Further, we illustrated the use of E2 (PI3Kα/IC 50 = 0.068 μM, T47D cell viability: IC50 = 0.9 μM) to block cancer cell proliferation and to monitor its subcellular localization by fluorescence microscopy.",

keywords = "Anticancer, Drug design, Fluorescent PI3K inhibitor, Intracellular distribution",

author = "Donghee Kim and Hyunseung Lee and Hwiseok Jun and Hong, {Soon Sun} and Sungwoo Hong",

note = "Funding Information: This research was supported by National Research Foundation of Korea (NRF) through general research grants (NRF-2010-0015340 and 2010-0022179), by the Korean Health Technology R&D Project (A101185), and by the National R&D Program for Cancer Control (1020250), Ministry for Health, Welfare and Family Affairs, Korea.",

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doi = "10.1016/j.bmc.2011.03.025",

language = "English",

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AU - Kim, Donghee

AU - Lee, Hyunseung

AU - Jun, Hwiseok

AU - Hong, Soon Sun

AU - Hong, Sungwoo

N1 - Funding Information: This research was supported by National Research Foundation of Korea (NRF) through general research grants (NRF-2010-0015340 and 2010-0022179), by the Korean Health Technology R&D Project (A101185), and by the National R&D Program for Cancer Control (1020250), Ministry for Health, Welfare and Family Affairs, Korea.

PY - 2011/4/15

Y1 - 2011/4/15

N2 - The monitoring of the drug behavior and distribution in biological system can provide information whether drug reaches its desired target, and a biological rationale for the design of new therapeutics. We have developed a family of potent fluorescent PI3Kα inhibitors in which part of the fluorophore was engineered to be a pharmacophore capable of inhibiting PI3Kα. These xanthine derivatives are characterized by a donor-acceptor molecular structure, and changes in the electronic properties of the two variation points at R1 and R2 give rise to notable bathochromic shifts in the λem, abs and increase the value of ΦF. Further, we illustrated the use of E2 (PI3Kα/IC 50 = 0.068 μM, T47D cell viability: IC50 = 0.9 μM) to block cancer cell proliferation and to monitor its subcellular localization by fluorescence microscopy.

AB - The monitoring of the drug behavior and distribution in biological system can provide information whether drug reaches its desired target, and a biological rationale for the design of new therapeutics. We have developed a family of potent fluorescent PI3Kα inhibitors in which part of the fluorophore was engineered to be a pharmacophore capable of inhibiting PI3Kα. These xanthine derivatives are characterized by a donor-acceptor molecular structure, and changes in the electronic properties of the two variation points at R1 and R2 give rise to notable bathochromic shifts in the λem, abs and increase the value of ΦF. Further, we illustrated the use of E2 (PI3Kα/IC 50 = 0.068 μM, T47D cell viability: IC50 = 0.9 μM) to block cancer cell proliferation and to monitor its subcellular localization by fluorescence microscopy.

KW - Anticancer

KW - Drug design

KW - Fluorescent PI3K inhibitor

KW - Intracellular distribution

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M3 - Article

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SN - 0968-0896

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SP - 2508

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JO - Bioorganic and Medicinal Chemistry

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IS - 8

ER -

Fluorescent phosphoinositide 3-kinase inhibitors suitable for monitoring of intracellular distribution

Abstract

Bibliographical note

Keywords

UN SDGs

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