Abstract
Saccharomonospora
sp. UR22 and
Dietzia
sp. UR66, two actinomycetes derived from the Red Sea sponge
Callyspongia siphonella
, were co-cultured and the induced metabolites were monitored by HPLC-DAD and TLC. Saccharomonosporine A (
1
), a novel brominated oxo-indole alkaloid, convolutamydine F (
2
) along with other three known induced metabolites (
3-5
) were isolated from the EtOAc extract of
Saccharomonospora
sp. UR22 and
Dietzia
sp. UR66 co-culture. Additionally, axenic culture of
Saccharomonospora
sp. UR22 led to isolation of six known microbial metabolites (
6-11
). A kinase inhibition assay results showed that compounds
1
and
3
were potent Pim-1 kinase inhibitors with an IC
50
value of 0.3 ± 0.02 and 0.95 ± 0.01 μM, respectively. Docking studies revealed the binding mode of compounds
1
and
3
in the ATP pocket of Pim-1 kinase. Testing of compounds
1
and
3
displayed significant antiproliferative activity against the human colon adenocarcinoma HT-29, (IC
50
3.6 and 3.7 μM, respectively) and the human promyelocytic leukemia HL-60, (IC
50
2.8 and 4.2 μM, respectively). These results suggested that compounds
1
and
3
act as potential Pim-1 kinase inhibitors that mediate the tumor cell growth inhibitory effect. This study highlighted the co-cultivation approach as an effective strategy to increase the chemical diversity of the secondary metabolites hidden in the genomes of the marine actinomycetes.