Lamellarin alkaloids: Isolation, synthesis, and biological activity

Fukuda, Tsutomu; Ishibashi, Fumito; Iwao, Masatomo

doi:10.1016/bs.alkal.2019.10.001

Cited by 53 publications

(59 citation statements)

References 163 publications

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“…To date, more than 65 lamellarins have been discovered since the first isolation of a member of this class by Faulkner et al in 1985 [ 156 , 157 ]. Divided into type I (with subsections a and b, comprising compounds with a saturated or unsaturated C-5–C-6 unit, respectively) containing a doubly annellated 2,3,4-triarylpyrrole core in form of a 1-aryl-6 H -chromeno-[4′,3′:4,5]pyrrolo-[2,1-a]isoquinolin-6-one or type II with a simple 3,4-diarylpyrrol-2-carboxylate ring system, the lamellarins comprise a large and prominent class of marine alkaloids.…”

Section: Non-halogenated Marine Pyrrole Alkaloidsmentioning

confidence: 99%

“…Divided into type I (with subsections a and b, comprising compounds with a saturated or unsaturated C-5–C-6 unit, respectively) containing a doubly annellated 2,3,4-triarylpyrrole core in form of a 1-aryl-6 H -chromeno-[4′,3′:4,5]pyrrolo-[2,1-a]isoquinolin-6-one or type II with a simple 3,4-diarylpyrrol-2-carboxylate ring system, the lamellarins comprise a large and prominent class of marine alkaloids. These compounds, derived from sponges, tunicates, and mollusks, exhibit a broad range of often highly potent biological activities, making them interesting targets for synthetic chemists [ 157 , 158 ].…”

Section: Non-halogenated Marine Pyrrole Alkaloidsmentioning

confidence: 99%

“…In both cases, the antibacterial activity appears to increase with an increasing degree of chlorination on the bisindole backbone [149]. In addition to studies on the biosynthetic gene cluster of Streptomyces SCSIO 03,032 [150], the group of Zhang, responsible for the isolation of spiroindimicins A-D (155)(156)(157)(158), discovered the halogenase SpmH involved in the biosynthesis of SPMs and IDMs.…”

Section: Scheme 12mentioning

confidence: 99%

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Marine Pyrrole Alkaloids

2021

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Nitrogen heterocycles are essential parts of the chemical machinery of life and often reveal intriguing structures. They are not only widespread in terrestrial habitats but can also frequently be found as natural products in the marine environment. This review highlights the important class of marine pyrrole alkaloids, well-known for their diverse biological activities. A broad overview of the marine pyrrole alkaloids with a focus on their isolation, biological activities, chemical synthesis, and derivatization covering the decade from 2010 to 2020 is provided. With relevant structural subclasses categorized, this review shall provide a clear and timely synopsis of this area.

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Section: Non-halogenated Marine Pyrrole Alkaloidsmentioning

confidence: 99%

Section: Non-halogenated Marine Pyrrole Alkaloidsmentioning

confidence: 99%

Section: Scheme 12mentioning

confidence: 99%

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Marine Pyrrole Alkaloids

2021

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“…Lamellarins are natural marine alkaloids originally isolated from the prosobranch mollusk Lamellaria sp. They structurally belong to 3,4‐dihydroxyphenylalanine (DOPA) derivatives 31‐33 . Lamellarins show various biological activities, such as inhibitions of DNA topoisomerase I (Topo I), 34 HIV integrase, 35 and serine/threonine kinases, including cyclin‐dependent kinases (CDKs) and glycogen synthase kinase (GSK)‐3α/β, protooncogene serine/threonine‐protein kinase (PIM)1, and dual‐specificity tyrosine‐phosphorylation‐regulated kinase (DYRK)1A 36 .…”

Section: Introductionmentioning

confidence: 99%

“…They structurally belong to 3,4-dihydroxyphenylalanine (DOPA) derivatives. [31][32][33] Lamellarins show various biological activities, such as inhibitions of DNA topoisomerase I (Topo I), 34 HIV integrase, 35 and serine/threonine kinases, including cyclin-dependent kinases (CDKs) and glycogen synthase kinase (GSK)-3α/β, protooncogene serine/threonine-protein kinase (PIM)1, and dual-specificity tyrosine-phosphorylation-regulated kinase (DYRK)1A. 36 The strong but nonselective kinase inhibitory activity of LamN can be harnessed by axial chirality-specific derivatization.…”

Section: Introductionmentioning

confidence: 99%

Lamellarin 14, a derivative of marine alkaloids, inhibits the T790M/C797S mutant epidermal growth factor receptor

et al. 2021

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The emergence of acquired resistance is a major concern associated with molecularly targeted kinase inhibitors. The C797S mutation in the epidermal growth factor receptor (EGFR) confers resistance to osimertinib, a third‐generation EGFR‐tyrosine kinase inhibitor (EGFR‐TKI). We report that the derivatization of the marine alkaloid topoisomerase inhibitor lamellarin N provides a structurally new class of EGFR‐TKIs. One of these, lamellarin 14, is effective against the C797S mutant EGFR. Bioinformatic analyses revealed that the derivatization transformed the topoisomerase inhibitor‐like biological activity of lamellarin N into kinase inhibitor‐like activity. Ba/F3 and PC‐9 cells expressing the EGFR in‐frame deletion within exon 19 (del ex19)/T790M/C797S triple‐mutant were sensitive to lamellarin 14 in a dose range similar to the effective dose for cells expressing EGFR del ex19 or del ex19/T790M. Lamellarin 14 decreased the autophosphorylation of EGFR and the downstream signaling in the triple‐mutant EGFR PC‐9 cells. Furthermore, intraperitoneal administration of 10 mg/kg lamellarin 14 for 17 days suppressed tumor growth of the triple‐mutant EGFR PC‐9 cells in a mouse xenograft model using BALB/c nu/nu mice. Thus, lamellarin 14 serves as a novel structural backbone for an EGFR‐TKI that prevents the development of cross‐resistance against known drugs in this class.

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Advances in C(sp²)−H/C(sp²)−H Oxidative Coupling of (Hetero)arenes Using 3d Transition Metal Catalysts

2021

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C−H/C−H oxidative coupling has emerged as a straightforward and powerful technique for the construction of (hetero)biaryls, with substantial application to drug discovery, agrochemicals, biology, and material sciences. Mainly aryl‐aryl, aryl‐heteroaryl, and heteroaryl‐heteroaryl couplings via double C(sp2)−H activation using 4d or 5d noble transition metal catalysts have been extensively studied. Considering the earth‐abundant and inexpensive nature of 3d transition metals, the sustainable development of C(sp2)−H/C(sp2)−H oxidative coupling employing such metal catalysts has gained significant attention. In this review, we present a comprehensive overview of C(sp2)−H/C(sp2)−H oxidative coupling of (hetero)arenes catalyzed by 3d transition metals.

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Lamellarin alkaloids: Isolation, synthesis, and biological activity

Cited by 53 publications

References 163 publications

Marine Pyrrole Alkaloids

Marine Pyrrole Alkaloids

Lamellarin 14, a derivative of marine alkaloids, inhibits the T790M/C797S mutant epidermal growth factor receptor

Advances in C(sp²)−H/C(sp²)−H Oxidative Coupling of (Hetero)arenes Using 3d Transition Metal Catalysts

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Lamellarin alkaloids: Isolation, synthesis, and biological activity

Cited by 53 publications

References 163 publications

Marine Pyrrole Alkaloids

Marine Pyrrole Alkaloids

Lamellarin 14, a derivative of marine alkaloids, inhibits the T790M/C797S mutant epidermal growth factor receptor

Advances in C(sp2)−H/C(sp2)−H Oxidative Coupling of (Hetero)arenes Using 3d Transition Metal Catalysts

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Advances in C(sp²)−H/C(sp²)−H Oxidative Coupling of (Hetero)arenes Using 3d Transition Metal Catalysts