CC BY
8
Vestnik FEB RAS. 2018. № 6 Supplement
UDC 547.996:593.4+547.925:593.4+547.996:593.58+547.996+593.31+577.115:593.4
DOI: 10.25808/08697698.2018.202.6S.023
T.N. MAKARIEVA, L.K. SHUBINA, A G. GUZII, E.K. KUDRYASHOVA, V.A. STONIK
Search and structural studies
of secondary metabolites
from Far Eastern marine invertebrates
Search, structural studies of new secondary metabolites and biological activities done in the Laboratory of Marine Natural Product Chemistry are reviewed. The main biological sources of these compounds were proved to be Far Eastern marine invertebrates, such as sponges, hydroids, as well as polychaete. Emphasis is directed to the unusual alkaloids, glycolipids, and polyhydroxysteroids which were recently isolated during 2013-2018.
Key words: secondary metabolites, marine sponges, hydroids, polychaete, alkaloids, glycolipids, polyhydroxysteroids
Marine invertebrates have long been known as a prolific source for the discovery of bioactive secondary metabolites. Most research in this area has been focused on invertebrates from tropical waters, but more recently the focus has shifted to the less accessible invertebrates of temperate and colder waters. A potentially fruitful opportunity for search of new marine secondary metabolites lies within the Northwestern Pacific region, where promising search for new natural products has been completed. The most common marine invertebrates of the region are sponges and echinoderms. In our laboratory about 300 natural compounds from numerous species of the Far Eastern marine invertebrates have been isolated, the corresponding chemical structures established, and biological activities studied. These substances belong to a wide variety of biogenetic classes including polar steroids (more 100), triterpene glycosides (about 100), and alkaloids (about 50). Up to day we have collected 3939 samples of marine organisms during 15 scientific cruises on board the research vessel "Akademik Oparin" at the period 1986 to 2017 from the Northwestern Pacific region mainly near the Kuril Islands. In result, urupocidins A and B with an unprecedented skeleton system have been isolated from the Far Eastern sponge Monanchora pulchra, are noticeable examples of recently discovered novel marine bioactive secondary metabolites. Urupocidin A increases nitric oxide production in murine macrophages via inducing iNOS expression [4].
* MAKARIEVA Tatyana Nikolaevna - DSc, Principal Researcher, SHUBINA Larisa Kimovna - PhD, Senior Researcher, GUZII Alla Grigorievna - PhD, Senior Researcher, KUDRYASHOVA Ekaterina Konstatinovna - Junior Researcher, STONIK Valentin Aronovich - DSc, Academician (G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS, Vladivostok, Russia). *E-mail: makarieva@piboc.dvo.ru
This work was supported by the Russian Science Foundation (Grant 17-14-01065).
OH Urupocidin B
NH
X
N NH2 i
OH
Two new natural products, 6-bromogramine and bis-6-bromogramine, inducing NF-kB activity, have been isolated from the marine Far-Eastern hydroid Abietinaria abietina [2].
Br
CH3
Br
Br
6-Bromogramine
Bis-6-bromogramine
Pulchranin A, the first nonpeptide TRPV1 channel inhibitor, and two its homologic acyclic alkaloids were isolated from the Far Eastern marine sponge Monanchora pulchra. We have found that activity of pulchranins decreased in the row pulchranin A - pulchranin B - pulchranin C and in the row TRPV1- TRPV3 - TRPA1. So, we propose that the hydroxylated alkenyl moiety plays an important role in inhibitory activity of pulchranins [3, 5, 6].
14
OH
NH,
. X
N f NH H
Pulchranin A 12
OH
13
NH,
A,
OH
Pulchranin B
NH,
A
NH
NH
Pulchranin C
As a result of the first study on secondary metabolites from the cosmopolitan bioluminescent marine tube polychaete Chaetopterus variopedatus, a new bicyclic guanidine alkaloid 6-epi-monanc horindong withthepreviously knownmonanchorin we re isolated [7].
Unprecedented bipolar glycolipids, melonoside A and its analogues, have been isolated from the Far-Eastern marine sponge Melonanchora kobjakovae. Melonoside A induces autophagy of human cisplatin-resistantgerminaltumorcellsNCCIT-R[1].
Melonoside A
Recently we have been isolated from Far Eastern sponge Haliclona sp. new structurally unique sulfated polyhydroxysteroids named by us gracilosulfates A-C. The structures of new secondary metabolites were elucidated by NMR, MS analysis and chemical transformations.
Herein we discuss tiiediversityofunusual secondaiy metabolitesfromFar Eastern marine invertebrates as well as the details of their structure elucidation and provide insights into their bioto^cal aativilies.
REFuamcamm :
1. Guzii A.G., Makarieva T.N., Denisenko V.A., Dmitrenok P.S., Kuzmich A.S., Dyshlovoy S.A., von Amsberg
G., Krasokhin V.B., Stonik V.A. Melonoside A: an ra-glycosylated fatty acid amide from the Far Eastern marine sponge Melonanchora kobjakovae // Org. Lett. 2016. Vol. 1, N 14. P. 3478-3481.
2. Guzii A.G., Makarieva T.N., Fedorov S.N., Denisenko V.A., Dmitrenok P.S., Kuzmich A.S., Krasokhin V.B., Lee
H.S., Lee Y.J., Stonik V.A. Gramine-derived bromo-alkaloids activating NF-KB-dependent transcription from the marine hydroid Abietinaria abietina // Nat. Prod. Commun. 2016. Vol. 11, N 9. P. 1263-1265.
3. Guzii A.G., Makarieva T.N., Korolkova Y.V., Andreev Y.A., Mosharova I.V., Tabakmaher K.M., Denisenko V. A., Dmitrenok P.S., Ogurtsova E.K., Antonov A.S., Lee H.S., Grishin E.V. Pulchranin A, isolated from the Far-Eastern marine sponge, Monanchora pulchra: the first marine non-peptide inhibitor of TRPV-1 channels // Tetrahedron Lett. 2013. Vol. 54. P. 1247-1250.
4. Makarieva T.N., Ogurtsova E.K., Denisenko V.A., Dmitrenok P.S., Tabakmakher K.M., Guzii A.G., Pislyagin E.A., Es'kov A.A., Kozhemyako V.B., Aminin D.L., Wang Y.-M., Stonik V.A. Urupocidin A: a new, inducing iNOS expression bicyclic guanidine alkaloid from the marine sponge Monanchora pulchra // Org. Lett. 2014. Vol. 16, N 16. P. 4292-4295.
5. Makarieva T.N., Ogurtsova E.K., Korolkova Y.V., Andreev Y.A., Mosharova I.V., Tabakmaher K.M., Guzii A.G., Denisenko V.A., Dmitrenok P.S., Grishin E.V., Stonik V.A. Pulchranins B and C, new acyclic guanidine alkaloids from the Far-Eastern marine sponge Monanchora pulchra // Nat. Prod. Commun. 2013. Vol. 8, N 9. P. 1229-1232.
6. Ogurtsova E.K., Makarieva T.N., Korolkova Y.V., Andreev Y.A., Mosharova I.V., Denisenko V.A., Dmitrenok P.S., Lee Y.J., Grishin E.V., Stonik V.A. New derivatives of natural acyclic guanidine alkaloids with TRPV receptor-regulating properties // Nat. Prod. Commun. 2015. Vol. 10, N 7. P. 1171-1173.
7. Shubina L.K., Makarieva T.N., Denisenko V.A., Dmitrenok P.S., Dyshlovoy S.A., von Amsberg G., Glazunov V.P., Silchenko A.S., Stonik I.V., Lee H.S., Lee Y.J., Stonik V. In order to determine the location of the corresponding carbonyl group in minor two-headed sphingolipids, .A. Absolute configuration and body part distribution of alkaloid 6-epi-monanchorin from the marine polychaete Chaetopterus variopedatus // Nat. Prod. Commun. 2016. Vol. 11, N 9. P. 1253-1257.
