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

Research output: Contribution to journalArticle

14 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 languageEnglish
Pages (from-to)7456-7460
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number24
DOIs
Publication statusPublished - 2012 Dec 15

Fingerprint

Diacylglycerol O-Acyltransferase
Triglycerides
Derivatives
Cholesterol
Hep G2 Cells
High Fat Diet
Liver Microsomes
Nutrition
Liver
LDL Cholesterol
HDL Cholesterol
Inhibitory Concentration 50
Weight Gain
Rats
Blood
Fats
Body Weight
Neoplasms
benzimidazole

Keywords

  • Benzimidazole
  • DGAT
  • DGAT inhibitors
  • Obesity
  • Triglycerides
  • Type II diabetes

ASJC Scopus subject areas

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

Cite this

Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors. / Lee, Kyeong; Goo, Ja Il; Jung, Hwa Young; Kim, Minkyoung; Boovanahalli, Shanthaveerappa K.; Park, Hye Ran; Kim, Mun Ock; Kim, Dong Hyun; Lee, Hyun Sun; Choi, Yongseok.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 24, 15.12.2012, p. 7456-7460.

Research output: Contribution to journalArticle

Lee, K, Goo, JI, Jung, HY, Kim, M, Boovanahalli, SK, Park, HR, Kim, MO, Kim, DH, Lee, HS & Choi, Y 2012, 'Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 24, pp. 7456-7460. https://doi.org/10.1016/j.bmcl.2012.10.046
Lee, Kyeong ; Goo, Ja Il ; Jung, Hwa Young ; Kim, Minkyoung ; Boovanahalli, Shanthaveerappa K. ; Park, Hye Ran ; Kim, Mun Ock ; Kim, Dong Hyun ; Lee, Hyun Sun ; Choi, Yongseok. / Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2012 ; Vol. 22, No. 24. pp. 7456-7460.
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