New Pim-1 Kinase Inhibitor From the Co-culture of Two Sponge-Associated Actinomycetes

sp. UR22 and sp. UR66, two actinomycetes derived from the Red Sea sponge , were co-cultured and the induced metabolites were monitored by HPLC-DAD and TLC. Saccharomonosporine A ( ), a novel brominated oxo-indole alkaloid, convolutamydine F ( ) along with other three known induced metabolites ( ) we...

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Bibliographic Details
Published in:Frontiers in chemistry 2018-11, Vol.6, p.538-538
Main Authors: El-Hawary, Seham S, Sayed, Ahmed M, Mohammed, Rabab, Khanfar, Mohammad A, Rateb, Mostafa E, Mohammed, Tarek A, Hajjar, Dina, Hassan, Hossam M, Gulder, Tobias A M, Abdelmohsen, Usama Ramadan
Format: Article
Language:English
Subjects:
actinomycetes
Chemistry
convolutamydine F
Dietzia sp
docking
Saccharomonospora sp
Saccharomonosporine A
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Summary:sp. UR22 and sp. UR66, two actinomycetes derived from the Red Sea sponge , were co-cultured and the induced metabolites were monitored by HPLC-DAD and TLC. Saccharomonosporine A ( ), a novel brominated oxo-indole alkaloid, convolutamydine F ( ) along with other three known induced metabolites ( ) were isolated from the EtOAc extract of sp. UR22 and sp. UR66 co-culture. Additionally, axenic culture of sp. UR22 led to isolation of six known microbial metabolites ( ). A kinase inhibition assay results showed that compounds and were potent Pim-1 kinase inhibitors with an IC value of 0.3 ± 0.02 and 0.95 ± 0.01 μM, respectively. Docking studies revealed the binding mode of compounds and in the ATP pocket of Pim-1 kinase. Testing of compounds and displayed significant antiproliferative activity against the human colon adenocarcinoma HT-29, (IC 3.6 and 3.7 μM, respectively) and the human promyelocytic leukemia HL-60, (IC 2.8 and 4.2 μM, respectively). These results suggested that compounds and 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.
ISSN:2296-2646
2296-2646
DOI:10.3389/fchem.2018.00538