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

Keywords

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

UN SDGs

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

Access to Document

10.1016/j.bmcl.2009.07.127

Cite this

@article{fcea13229d9f46d5b9636d7bf53d20c4,

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",

year = "2009",

month = sep,

day = "15",

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

language = "English",

volume = "19",

pages = "5376--5379",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "18",

}

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 - http://www.scopus.com/inward/record.url?scp=68949132702&partnerID=8YFLogxK

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

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this