Pim kinase inhibitory and antiproliferative activity of a novel series of meridianin C derivatives

Kunal N More; Hyo Weon Jang; Victor S Hong; Jinho Lee

doi:10.1016/j.bmcl.2014.04.035

Pim kinase inhibitory and antiproliferative activity of a novel series of meridianin C derivatives

Bioorg Med Chem Lett. 2014 Jun 1;24(11):2424-8. doi: 10.1016/j.bmcl.2014.04.035. Epub 2014 Apr 16.

Authors

Kunal N More¹, Hyo Weon Jang², Victor S Hong³, Jinho Lee⁴

Affiliations

¹ Department of Chemistry, Keimyung University, Daegu 704-701, Republic of Korea.
² Department of Chemistry, Sunchon National University, Sunchon, Chonnam 540-742, Republic of Korea.
³ Department of Chemistry, Keimyung University, Daegu 704-701, Republic of Korea. Electronic address: victorh@kmu.ac.kr.
⁴ Department of Chemistry, Keimyung University, Daegu 704-701, Republic of Korea. Electronic address: jinho@kmu.ac.kr.

PMID: 24775304
DOI: 10.1016/j.bmcl.2014.04.035

Abstract

A novel series of meridianin C derivatives substituted at C-5 position were prepared. These derivatives were tested for their kinase inhibitory potencies against all three family members of the pim kinases (Pim-1, Pim-2 and Pim-3). In addition, their antiproliferative activity towards three human leukemia cell lines as MV4-11, Jurkat clone E6-1 and K562 has been evaluated. Structure activity relationships at C-3 and C-5 positions of indole were performed to better understand the mechanism behind the enhanced potency. Compound 7f, the most active compound of the series showed a single-digit nanomolar IC50 with selectivity towards Pim-1 kinase.

Keywords: 3,5-Disubstituted indole; Antiproliferative activity; Inhibitor; Meridianin C; Pim kinase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Caco-2 Cells
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Ethylenediamines / chemical synthesis
Ethylenediamines / chemistry
Ethylenediamines / pharmacology*
Humans
Indoles / chemical synthesis
Indoles / chemistry
Indoles / pharmacology*
Jurkat Cells
K562 Cells
Models, Molecular
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
Proto-Oncogene Proteins c-pim-1 / metabolism
Structure-Activity Relationship

Substances

Antineoplastic Agents
Ethylenediamines
Indoles
N1-(6-(3-(2-aminopyrimidin-4-yl)-1H-indol-5-yl)pyrazin-2-yl)-N2,N2-dimethylethane-1,2-diamine
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-pim-1
proto-oncogene proteins pim