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.