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Biological Activity of Recently Discovered Halogenated Marine Natural Products.

Gribble GW - Mar Drugs (2015)

Bottom Line: This review presents the biological activity-antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity-of halogenated marine natural products discovered in the past five years.Newly discovered examples that do not report biological activity are not included.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA. gordon.w.gribble@dartmouth.edu.

ABSTRACT
This review presents the biological activity-antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity-of halogenated marine natural products discovered in the past five years. Newly discovered examples that do not report biological activity are not included.

No MeSH data available.


Structures of dispacamide E (585) and pyrrole 586 from the sponges Stylissa massa and Stylissa flabelliformis [207].
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marinedrugs-13-04044-f113: Structures of dispacamide E (585) and pyrrole 586 from the sponges Stylissa massa and Stylissa flabelliformis [207].

Mentions: Several marine brominated natural products are protein kinase inhibitors. Purpuroines A (59) and D (62) (Figure 11) are selective inhibitors of the kinase LCK (lymphocyte-specific protein tyrosine kinase) with IC50 2.35 and 0.94 µg/mL, respectively. Purpuroine D is inhibitory towards PLK1 (serine/threonine-protein kinase) with IC50 0.94 µg/mL. For comparison, staurosporine shows IC50 3.73 and 0.92 µg/mL for LCK and PLK1, respectively. All of the purpuroines are weak inhibitors to CDK2 (cyclin-dependent kinase 2) (IC50 > 50 µg/mL) [46]. The study of the massadines (Figure 12) re-established that the known debromohymenialdisine and hymenialdisine are nanomolar kinase inhibitors of CDK5/P25 (cyclin-dependent kinase 5), CD1δ (casein kinase 1), and GSK3β (glycogen synthase kinase 3β): IC50 0.4, 0.1, and 0.2 µM, respectively, for debromohymenialdisine, and IC50 0.16, 0.03, and 0.07 µM, respectively, for hymenialdisine [47]. The novel sesquibastadin 1 (367) and bastadin 3 (Figure 71) are strong inhibitors of at least 22 protein kinases (IC50 0.1–6.5 µM). For example sesquibastadin 1 causes potent inhibition of the receptor tyrosine kinases EGF-R and VEGF-R2 (both IC50 0.6 µM), and of T1E2 (IC50 0.6 µM). Bastadin 3 is a potent inhibitor of Aurora A and B (IC50 0.1 and 0.5 µM, respectively). This bastadin inhibits all of the examined kinases at submicromolar activity. The other bastadins 6, 7, 11, and 16 are either inactive or much less active, exactly the opposite to their cell proliferation inhibitory activity (vide supra) [139]. A study of the known ageladine A, and synthetic analogues, against a battery of kinases shows that ageladine A has modest activity towards the tyrosine kinase DYRK1A and Pim 1 [206]. The Indonesian sponges Stylissa massa and Stylissa flabelliformis yielded 25 bromopyrroles, including the new dispacamide E (585) and 586 (Figure 113) [207]. All isolated compounds were assayed against these protein kinases: DYRK1A, CDK5, GSK-3, CLK-1, CK-1, CDK1, CDK2/A, CDK9/cyclin T, and Plasmodium falciparum glycogen synthase kinase-3 (PfGSK-3). Dispacamide E is particularly active against GSK-3, DYRK1A and CK-1 (IC50 2.1, 6.2, and 4.9 µM, respectively). The known hymenine and some hymenialdisine derivatives are very active against PfGSK-3 with IC50 in the nanomolar range [207]. The red alga Laurencia similis from the Hainan coast, China, has afforded five new polybrominated compounds, 587–591 (Figure 114) [208]. The brominated N-bromo-2-naphthylamines 588–590 are remarkably unique structures, unlike the brominated diphenyl ether 587 and benzophenone 591, for which many examples are known. Metabolites 587 and 591 are inhibitory towards PTP1B (protein tyrosine phosphatase B) with IC50 2.97 and 2.66 µM, respectively. The Yesinia outer protein (YopE), which is also a protein tyrosine phosphatase, is inhibited by pseudoceramines B (52) and D (54) (Figure 9), with IC50 19 and 6 µM, respectively [44]. This enzyme is essential for bacterial virulence of the Gram-negative Yersinia spp.


Biological Activity of Recently Discovered Halogenated Marine Natural Products.

Gribble GW - Mar Drugs (2015)

Structures of dispacamide E (585) and pyrrole 586 from the sponges Stylissa massa and Stylissa flabelliformis [207].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4515607&req=5

marinedrugs-13-04044-f113: Structures of dispacamide E (585) and pyrrole 586 from the sponges Stylissa massa and Stylissa flabelliformis [207].
Mentions: Several marine brominated natural products are protein kinase inhibitors. Purpuroines A (59) and D (62) (Figure 11) are selective inhibitors of the kinase LCK (lymphocyte-specific protein tyrosine kinase) with IC50 2.35 and 0.94 µg/mL, respectively. Purpuroine D is inhibitory towards PLK1 (serine/threonine-protein kinase) with IC50 0.94 µg/mL. For comparison, staurosporine shows IC50 3.73 and 0.92 µg/mL for LCK and PLK1, respectively. All of the purpuroines are weak inhibitors to CDK2 (cyclin-dependent kinase 2) (IC50 > 50 µg/mL) [46]. The study of the massadines (Figure 12) re-established that the known debromohymenialdisine and hymenialdisine are nanomolar kinase inhibitors of CDK5/P25 (cyclin-dependent kinase 5), CD1δ (casein kinase 1), and GSK3β (glycogen synthase kinase 3β): IC50 0.4, 0.1, and 0.2 µM, respectively, for debromohymenialdisine, and IC50 0.16, 0.03, and 0.07 µM, respectively, for hymenialdisine [47]. The novel sesquibastadin 1 (367) and bastadin 3 (Figure 71) are strong inhibitors of at least 22 protein kinases (IC50 0.1–6.5 µM). For example sesquibastadin 1 causes potent inhibition of the receptor tyrosine kinases EGF-R and VEGF-R2 (both IC50 0.6 µM), and of T1E2 (IC50 0.6 µM). Bastadin 3 is a potent inhibitor of Aurora A and B (IC50 0.1 and 0.5 µM, respectively). This bastadin inhibits all of the examined kinases at submicromolar activity. The other bastadins 6, 7, 11, and 16 are either inactive or much less active, exactly the opposite to their cell proliferation inhibitory activity (vide supra) [139]. A study of the known ageladine A, and synthetic analogues, against a battery of kinases shows that ageladine A has modest activity towards the tyrosine kinase DYRK1A and Pim 1 [206]. The Indonesian sponges Stylissa massa and Stylissa flabelliformis yielded 25 bromopyrroles, including the new dispacamide E (585) and 586 (Figure 113) [207]. All isolated compounds were assayed against these protein kinases: DYRK1A, CDK5, GSK-3, CLK-1, CK-1, CDK1, CDK2/A, CDK9/cyclin T, and Plasmodium falciparum glycogen synthase kinase-3 (PfGSK-3). Dispacamide E is particularly active against GSK-3, DYRK1A and CK-1 (IC50 2.1, 6.2, and 4.9 µM, respectively). The known hymenine and some hymenialdisine derivatives are very active against PfGSK-3 with IC50 in the nanomolar range [207]. The red alga Laurencia similis from the Hainan coast, China, has afforded five new polybrominated compounds, 587–591 (Figure 114) [208]. The brominated N-bromo-2-naphthylamines 588–590 are remarkably unique structures, unlike the brominated diphenyl ether 587 and benzophenone 591, for which many examples are known. Metabolites 587 and 591 are inhibitory towards PTP1B (protein tyrosine phosphatase B) with IC50 2.97 and 2.66 µM, respectively. The Yesinia outer protein (YopE), which is also a protein tyrosine phosphatase, is inhibited by pseudoceramines B (52) and D (54) (Figure 9), with IC50 19 and 6 µM, respectively [44]. This enzyme is essential for bacterial virulence of the Gram-negative Yersinia spp.

Bottom Line: This review presents the biological activity-antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity-of halogenated marine natural products discovered in the past five years.Newly discovered examples that do not report biological activity are not included.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA. gordon.w.gribble@dartmouth.edu.

ABSTRACT
This review presents the biological activity-antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity-of halogenated marine natural products discovered in the past five years. Newly discovered examples that do not report biological activity are not included.

No MeSH data available.