Pim kinase inhibitory and antiproliferative activity of a novel series of meridianin C derivatives.
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.
Department of Chemistry, Keimyung University, Daegu 704-701, Republic of Korea.
Kunal N
KN
More
Department of Chemistry, Sunchon National University, Sunchon, Chonnam 540-742, Republic of Korea.
Hyo Weon
HW
Jang
Department of Chemistry, Keimyung University, Daegu 704-701, Republic of Korea. Electronic address: victorh@kmu.ac.kr.
Victor S
VS
Hong
Department of Chemistry, Keimyung University, Daegu 704-701, Republic of Korea. Electronic address: jinho@kmu.ac.kr.
Jinho
J
Lee
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005029:Ethylenediamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019169:Jurkat Cells; D020014:K562 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005029:Ethylenediamines; D007211:Indoles; C000593985:N1-(6-(3-(2-aminopyrimidin-4-yl)-1H-indol-5-yl)pyrazin-2-yl)-N2,N2-dimethylethane-1,2-diamine; D047428:Protein Kinase Inhibitors; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim
3,5-Disubstituted indole; Antiproliferative activity; Inhibitor; Meridianin C; Pim kinase