Synthesis and biological activity of analogues of ptilomycalin A

Black, Gregory P.; Coles, Simon J.; Hizi, Amnon; Howard-Jones, Andrew; Hursthouse, Michael B.; McGown, Alan T.; Loya, Shoshana; Moore, Christopher; Murphy, P. J.; Smith, Nigel; Walshe, Nigel

doi:10.1016/s0040-4039(01)00400-2

Cited by 23 publications

(6 citation statements)

References 14 publications

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“…Recently, we were able to isolate it from the marine sponge Monanchora pulchra [ 17 ]. This alkaloid has shown a potent cytotoxicity against a broad panel of human cancer cells [ 16 , 18 , 19 , 20 ]. However, to date molecular targets and the mode of action of ptilomycalin A in mammalian cell have not been studied.…”

Section: Introductionmentioning

confidence: 99%

Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro

et al. 2016

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Guanidine alkaloids from sponges Monanchora spp. represent diverse bioactive compounds, however, the mechanisms underlying bioactivity are very poorly understood. Here, we report results of studies on cytotoxic action, the ability to inhibit EGF-induced neoplastic transformation, and the effects on MAPK/AP-1 signaling of eight rare guanidine alkaloids, recently isolated from the marine sponge Monanchora pulchra, namely: monanchocidin A (1), monanchocidin B (2), monanchomycalin C (3), ptilomycalin A (4), monanchomycalin B (5), normonanchocidin D (6), urupocidin A (7), and pulchranin A (8). All of the compounds induced cell cycle arrest (apart from 8) and programmed death of cancer cells. Ptilomycalin A-like compounds 1–6 activated JNK1/2 and ERK1/2, following AP-1 activation and caused p53-independent programmed cell death. Compound 7 induced p53-independent cell death without activation of AP-1 or caspase-3/7, and the observed JNK1/2 activation did not contribute to the cytotoxic effect of the compound. Alkaloid 8 induced JNK1/2 (but not ERK1/2) activation leading to p53-independent cell death and strong suppression of AP-1 activity. Alkaloids 1–4, 7, and 8 were able to inhibit the EGF-induced neoplastic transformation of JB6 P+ Cl41 cells. Our results suggest that investigated guanidine marine alkaloids hold potential to eliminate human cancer cells and prevent cancer cell formation and spreading.

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Section: Introductionmentioning

confidence: 99%

Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro

et al. 2016

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“…18d,e,f Compound 1 inhibited the DNA polymerase activity of HIV reverse transcriptase (60% at 10 μM). 29 The work described here reveals the first example of inhibition, by 1 , of an oxidase enzyme (laccase). Laccases are proteins characterized by tetranuclear copper belonging to the ‘blue copper oxidase’ family that includes ascorbate oxidase.…”

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confidence: 78%

Ptilomycalin A inhibits laccase and melanization in Cryptococcus neoformans

Dalisay

Saludes

Molinski

2011

Bioorganic & Medicinal Chemistry

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“…41 and tetracyclic guanidine 17 were prepared as previously described. [46][47][48][49][50][51][52] The naturally occurring guanidine alkaloid nitensidine D (18) 52 was prepared as its hydrochloride salt in 53% yield by the reaction of geranylamine with 1H-pyrazole-1-carboxamidine hydrochloride. Miltefosine was used as a standard drug.…”

Section: Immunomodulatory Potential Of Compounds Quantification Of Nmentioning

confidence: 99%

Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes

et al. 2016

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Synthetic analogues of marine sponge guanidine alkaloids showed in vitro antiparasitic activity against Leishmania (L.) infantum and Trypanosoma cruzi. Guanidines 10 and 11 presented the highest selectivity index when tested against Leishmania. The antiparasitic activity of 10 and 11 was investigated in host cells and in parasites. Both compounds induced depolarization of mitochondrial membrane potential, upregulation of reactive oxygen species levels, and increased plasma membrane permeability in Leishmania parasites. Immunomodulatory assays suggested an NO-independent effect of guanidines 10 and 11 on macrophages. The same compounds also promoted anti-inflammatory activity in L. (L.) infantum-infected macrophages cocultived with splenocytes, reducing the production of cytokines MCP-1 and IFN-γ. Guanidines 10 and 11 affect the bioenergetic metabolism of Leishmania, with selective elimination of parasites via a host-independent mechanism.

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Synthesis and biological activity of analogues of ptilomycalin A

Cited by 23 publications

References 14 publications

Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro

Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro

Ptilomycalin A inhibits laccase and melanization in Cryptococcus neoformans

Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes

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