A novel class of highly potent multidrug resistance reversal agents: Disubstituted adamantyl derivatives

Kyung Hoon Min; Yan Xia; Eun Kyung Kim; Yinglan Jin; Navneet Kaur; Eun Seon Kim; Dae Kyong Kim; Hwa Young Jung; Yongseok Choi; Mi Kyung Park; Yong Ki Min; Kiho Lee; Kyeong Lee

doi:10.1016/j.bmcl.2009.07.127

A novel class of highly potent multidrug resistance reversal agents: Disubstituted adamantyl derivatives

Kyung Hoon Min
, Yan Xia
, Eun Kyung Kim
, Yinglan Jin
, Navneet Kaur
, Eun Seon Kim
, Dae Kyong Kim
, Hwa Young Jung
, Yongseok Choi
, Mi Kyung Park
, Yong Ki Min
, Kiho Lee
, Kyeong Lee

Department of Pharmacy

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

15 Scopus citations

Abstract

Novel disubstituted adamantyl derivatives were synthesized and evaluated in a P-glycoprotein dependent multidrug resistance cancer cell line. The hit to lead optimization provided potent MDR reversal agents. Some potent adamantyl derivatives were more than 10-fold more potent than verapamil without considerable intrinsic cytotoxicity. The 3-trifluorophenyl derivative 14f did not affect the metabolism of CYP450 3A4, whereas most of MDR revertants had a weak inhibitory effect.

Original language	English
Pages (from-to)	5376-5379
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	18
DOIs	https://doi.org/10.1016/j.bmcl.2009.07.127
State	Published - 15 Sep 2009

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

ABC transporter
Adamantane
CYP3A4
MES-SA/DX5
Multidrug resistance
P-glycoprotein

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10.1016/j.bmcl.2009.07.127

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title = "A novel class of highly potent multidrug resistance reversal agents: Disubstituted adamantyl derivatives",

abstract = "Novel disubstituted adamantyl derivatives were synthesized and evaluated in a P-glycoprotein dependent multidrug resistance cancer cell line. The hit to lead optimization provided potent MDR reversal agents. Some potent adamantyl derivatives were more than 10-fold more potent than verapamil without considerable intrinsic cytotoxicity. The 3-trifluorophenyl derivative 14f did not affect the metabolism of CYP450 3A4, whereas most of MDR revertants had a weak inhibitory effect.",

keywords = "ABC transporter, Adamantane, CYP3A4, MES-SA/DX5, Multidrug resistance, P-glycoprotein",

author = "Min, \{Kyung Hoon\} and Yan Xia and Kim, \{Eun Kyung\} and Yinglan Jin and Navneet Kaur and Kim, \{Eun Seon\} and Kim, \{Dae Kyong\} and Jung, \{Hwa Young\} and Yongseok Choi and Park, \{Mi Kyung\} and Min, \{Yong Ki\} and Kiho Lee and Kyeong Lee",

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day = "15",

doi = "10.1016/j.bmcl.2009.07.127",

language = "English",

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TY - JOUR

T1 - A novel class of highly potent multidrug resistance reversal agents

T2 - Disubstituted adamantyl derivatives

AU - Min, Kyung Hoon

AU - Xia, Yan

AU - Kim, Eun Kyung

AU - Jin, Yinglan

AU - Kaur, Navneet

AU - Kim, Eun Seon

AU - Kim, Dae Kyong

AU - Jung, Hwa Young

AU - Choi, Yongseok

AU - Park, Mi Kyung

AU - Min, Yong Ki

AU - Lee, Kiho

AU - Lee, Kyeong

PY - 2009/9/15

Y1 - 2009/9/15

N2 - Novel disubstituted adamantyl derivatives were synthesized and evaluated in a P-glycoprotein dependent multidrug resistance cancer cell line. The hit to lead optimization provided potent MDR reversal agents. Some potent adamantyl derivatives were more than 10-fold more potent than verapamil without considerable intrinsic cytotoxicity. The 3-trifluorophenyl derivative 14f did not affect the metabolism of CYP450 3A4, whereas most of MDR revertants had a weak inhibitory effect.

AB - Novel disubstituted adamantyl derivatives were synthesized and evaluated in a P-glycoprotein dependent multidrug resistance cancer cell line. The hit to lead optimization provided potent MDR reversal agents. Some potent adamantyl derivatives were more than 10-fold more potent than verapamil without considerable intrinsic cytotoxicity. The 3-trifluorophenyl derivative 14f did not affect the metabolism of CYP450 3A4, whereas most of MDR revertants had a weak inhibitory effect.

KW - ABC transporter

KW - Adamantane

KW - CYP3A4

KW - MES-SA/DX5

KW - Multidrug resistance

KW - P-glycoprotein

UR - https://www.scopus.com/pages/publications/68949132702

U2 - 10.1016/j.bmcl.2009.07.127

DO - 10.1016/j.bmcl.2009.07.127

M3 - Article

C2 - 19679475

AN - SCOPUS:68949132702

SN - 0960-894X

VL - 19

SP - 5376

EP - 5379

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 18

ER -

A novel class of highly potent multidrug resistance reversal agents: Disubstituted adamantyl derivatives

Abstract

UN SDGs

Keywords

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