New Pim-1 Kinase Inhibitor From the Co-culture of Two Sponge-Associated Actinomycetes
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2018.00538/full |
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| author | Seham S. El-Hawary Ahmed M. Sayed Ahmed M. Sayed Rabab Mohammed Mohammad A. Khanfar Mohammad A. Khanfar Mostafa E. Rateb Mostafa E. Rateb Mostafa E. Rateb Tarek A. Mohammed Dina Hajjar Hossam M. Hassan Hossam M. Hassan Tobias A. M. Gulder Tobias A. M. Gulder Usama Ramadan Abdelmohsen |
| author_facet | Seham S. El-Hawary Ahmed M. Sayed Ahmed M. Sayed Rabab Mohammed Mohammad A. Khanfar Mohammad A. Khanfar Mostafa E. Rateb Mostafa E. Rateb Mostafa E. Rateb Tarek A. Mohammed Dina Hajjar Hossam M. Hassan Hossam M. Hassan Tobias A. M. Gulder Tobias A. M. Gulder Usama Ramadan Abdelmohsen |
| author_sort | Seham S. El-Hawary |
| collection | DOAJ |
| description | 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 IC50 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, (IC50 3.6 and 3.7 μM, respectively) and the human promyelocytic leukemia HL-60, (IC50 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. |
| first_indexed | 2024-04-13T14:53:22Z |
| format | Article |
| id | doaj.art-5c67695bd31343fda9e6d55344ba0df9 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-04-13T14:53:22Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Chemistry |
| spelling | doaj.art-5c67695bd31343fda9e6d55344ba0df92022-12-22T02:42:31ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462018-11-01610.3389/fchem.2018.00538403723New Pim-1 Kinase Inhibitor From the Co-culture of Two Sponge-Associated ActinomycetesSeham S. El-Hawary0Ahmed M. Sayed1Ahmed M. Sayed2Rabab Mohammed3Mohammad A. Khanfar4Mohammad A. Khanfar5Mostafa E. Rateb6Mostafa E. Rateb7Mostafa E. Rateb8Tarek A. Mohammed9Dina Hajjar10Hossam M. Hassan11Hossam M. Hassan12Tobias A. M. Gulder13Tobias A. M. Gulder14Usama Ramadan Abdelmohsen15Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, EgyptPharmacognosy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptPharmacognosy Department, Faculty of Pharmacy, Nahda University, Beni-Suef, EgyptPharmacognosy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptFaculty of Pharmacy, The University of Jordan, Amman, JordanCollege of Pharmacy, Alfaisal University, Riyadh, Saudi ArabiaPharmacognosy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptSchool of Computing, Engineering and Physical Sciences, University of the West of Scotland, Paisley, United KingdomMarine Biodiscovery Centre, University of Aberdeen, Aberdeen, United KingdomMarine Invertebrates, National Institute of Oceanography and Fisheries, Red Sea Branch, Hurghada, EgyptDepartment of Biochemistry, Faculty of Science, Center for Science and Medical Research, University of Jeddah, Jeddah, Saudi ArabiaPharmacognosy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptPharmacognosy Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt0Department of Chemistry and Center for Integrated Protein Science Munich (CIPSM), Biosystems Chemistry, Technical University of Munich, Garching, Germany1Chair of Technical Biochemistry, Technische Universität Dresden, Dresden, Germany2Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia, EgyptSaccharomonospora 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 IC50 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, (IC50 3.6 and 3.7 μM, respectively) and the human promyelocytic leukemia HL-60, (IC50 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.https://www.frontiersin.org/article/10.3389/fchem.2018.00538/fullSaccharomonospora sp.Dietzia sp.actinomycetesSaccharomonosporine Aconvolutamydine Fdocking |
| spellingShingle | Seham S. El-Hawary Ahmed M. Sayed Ahmed M. Sayed Rabab Mohammed Mohammad A. Khanfar Mohammad A. Khanfar Mostafa E. Rateb Mostafa E. Rateb Mostafa E. Rateb Tarek A. Mohammed Dina Hajjar Hossam M. Hassan Hossam M. Hassan Tobias A. M. Gulder Tobias A. M. Gulder Usama Ramadan Abdelmohsen New Pim-1 Kinase Inhibitor From the Co-culture of Two Sponge-Associated Actinomycetes Frontiers in Chemistry Saccharomonospora sp. Dietzia sp. actinomycetes Saccharomonosporine A convolutamydine F docking |
| title | New Pim-1 Kinase Inhibitor From the Co-culture of Two Sponge-Associated Actinomycetes |
| title_full | New Pim-1 Kinase Inhibitor From the Co-culture of Two Sponge-Associated Actinomycetes |
| title_fullStr | New Pim-1 Kinase Inhibitor From the Co-culture of Two Sponge-Associated Actinomycetes |
| title_full_unstemmed | New Pim-1 Kinase Inhibitor From the Co-culture of Two Sponge-Associated Actinomycetes |
| title_short | New Pim-1 Kinase Inhibitor From the Co-culture of Two Sponge-Associated Actinomycetes |
| title_sort | new pim 1 kinase inhibitor from the co culture of two sponge associated actinomycetes |
| topic | Saccharomonospora sp. Dietzia sp. actinomycetes Saccharomonosporine A convolutamydine F docking |
| url | https://www.frontiersin.org/article/10.3389/fchem.2018.00538/full |
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