Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors

Kyeong Lee; Ja Il Goo; Hwa Young Jung; Minkyoung Kim; Shanthaveerappa K. Boovanahalli; Hye Ran Park; Mun Ock Kim; Dong Hyun Kim; Hyun Sun Lee; Yongseok Choi

doi:10.1016/j.bmcl.2012.10.046

Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors

Kyeong Lee, Ja Il Goo, Hwa Young Jung, Minkyoung Kim, Shanthaveerappa K. Boovanahalli, Hye Ran Park, Mun Ock Kim, Dong Hyun Kim, Hyun Sun Lee, Yongseok Choi

Department of Biotechnology

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

17 Citations (Scopus)

Abstract

A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC₅₀= 4.4 μM) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level.

Original language	English
Pages (from-to)	7456-7460
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	24
DOIs	https://doi.org/10.1016/j.bmcl.2012.10.046
Publication status	Published - 2012 Dec 15

Keywords

Benzimidazole
DGAT
DGAT inhibitors
Obesity
Triglycerides
Type II diabetes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

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

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10.1016/j.bmcl.2012.10.046

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title = "Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors",

abstract = "A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC50= 4.4 μM) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level.",

keywords = "Benzimidazole, DGAT, DGAT inhibitors, Obesity, Triglycerides, Type II diabetes",

author = "Kyeong Lee and Goo, {Ja Il} and Jung, {Hwa Young} and Minkyoung Kim and Boovanahalli, {Shanthaveerappa K.} and Park, {Hye Ran} and Kim, {Mun Ock} and Kim, {Dong Hyun} and Lee, {Hyun Sun} and Yongseok Choi",

note = "Funding Information: This research was supported by grants from KRIBB Research Initiative Program, Basic Science Research Program through the National Research Fund from Ministry of Education, Science and Technology (# 2011-0026325 ), and GRRC ( dongguk-2012-B02 ), Republic of Korea. ",

year = "2012",

month = dec,

day = "15",

doi = "10.1016/j.bmcl.2012.10.046",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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AU - Lee, Kyeong

AU - Goo, Ja Il

AU - Jung, Hwa Young

AU - Kim, Minkyoung

AU - Boovanahalli, Shanthaveerappa K.

AU - Park, Hye Ran

AU - Kim, Mun Ock

AU - Kim, Dong Hyun

AU - Lee, Hyun Sun

AU - Choi, Yongseok

N1 - Funding Information: This research was supported by grants from KRIBB Research Initiative Program, Basic Science Research Program through the National Research Fund from Ministry of Education, Science and Technology (# 2011-0026325 ), and GRRC ( dongguk-2012-B02 ), Republic of Korea.

PY - 2012/12/15

Y1 - 2012/12/15

N2 - A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC50= 4.4 μM) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level.

AB - A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC50= 4.4 μM) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level.

KW - Benzimidazole

KW - DGAT

KW - DGAT inhibitors

KW - Obesity

KW - Triglycerides

KW - Type II diabetes

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DO - 10.1016/j.bmcl.2012.10.046

M3 - Article

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VL - 22

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EP - 7460

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

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ER -

Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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