Novel quinolinylaminoisoquinoline bioisosteres of sorafenib as selective RAF1 kinase inhibitors: Design, synthesis, and antiproliferative activity against melanoma cell line

Hye Jung Cho, Mohammed Ibrahim El-Gamal, Chang Hyun Oh, So Ha Lee, Taebo Sim, Garam Kim, Hong Seok Choi, Jung Hoon Choi, Kyung Ho Yoo

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Design and synthesis of a new series of quinolinylaminoisoquinoline derivatives as conformationally restricted bioisosteres of Sorafenib are described. Their in vitro antiproliferative activity against A375P melanoma cell line was tested. Compounds 1b, 1d, 1g, and 1j showed the highest potency against A375P cell line with IC50 values in sub-micromolar scale. In addition, compound 1d exerted high selectivity towards RAF1 serine/threonine kinase with 96.47% inhibition at 10 μM, and IC50 of 0.96 μM. This compound can possess antiproliferative activity against melanoma cells through inhibition of RAF1 kinase.

Original languageEnglish
Pages (from-to)747-756
Number of pages10
JournalChemical and Pharmaceutical Bulletin
Volume61
Issue number7
DOIs
Publication statusPublished - 2013 Jul 1

Fingerprint

Inhibitory Concentration 50
Melanoma
Phosphotransferases
Thermodynamic properties
Cells
Cell Line
Protein-Serine-Threonine Kinases
Derivatives
sorafenib
In Vitro Techniques

Keywords

  • Antiproliferative activity
  • Bioisostere
  • Melanoma
  • Quinolinylaminoisoquinoline
  • Sorafenib

ASJC Scopus subject areas

  • Drug Discovery
  • Chemistry(all)

Cite this

Novel quinolinylaminoisoquinoline bioisosteres of sorafenib as selective RAF1 kinase inhibitors : Design, synthesis, and antiproliferative activity against melanoma cell line. / Cho, Hye Jung; El-Gamal, Mohammed Ibrahim; Oh, Chang Hyun; Lee, So Ha; Sim, Taebo; Kim, Garam; Choi, Hong Seok; Choi, Jung Hoon; Yoo, Kyung Ho.

In: Chemical and Pharmaceutical Bulletin, Vol. 61, No. 7, 01.07.2013, p. 747-756.

Research output: Contribution to journalArticle

Cho, Hye Jung ; El-Gamal, Mohammed Ibrahim ; Oh, Chang Hyun ; Lee, So Ha ; Sim, Taebo ; Kim, Garam ; Choi, Hong Seok ; Choi, Jung Hoon ; Yoo, Kyung Ho. / Novel quinolinylaminoisoquinoline bioisosteres of sorafenib as selective RAF1 kinase inhibitors : Design, synthesis, and antiproliferative activity against melanoma cell line. In: Chemical and Pharmaceutical Bulletin. 2013 ; Vol. 61, No. 7. pp. 747-756.
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