Ptilomycalin A: a novel polycyclic guanidine alkaloid of marine origin

Kashman, Yoel; Hirsh, Shulamit; McConnell, Oliver J.; Ohtani, Ikuko I.; Kusumi, Takenori; Kakisawa, Hiroshi

doi:10.1021/ja00206a029

Cited by 169 publications

(133 citation statements)

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“…3,4 Ptilomycalin A 1 has a unique polycyclic guanidine skeleton with a spermidine group linked to a 16-hydroxyhexadecanoic acid moiety. [3][4][5] This novel guanidine alkaloid possesses remarkable antifungal, antiviral, and antitumor activities. [3][4][5] Ethanolic extract of abundant shallow water Red Sea sponge H. arabica was targeted because it inhibited the proliferation and invasion of the highly metastatic human prostate cancer PC-3M cell line.…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5] This novel guanidine alkaloid possesses remarkable antifungal, antiviral, and antitumor activities. [3][4][5] Ethanolic extract of abundant shallow water Red Sea sponge H. arabica was targeted because it inhibited the proliferation and invasion of the highly metastatic human prostate cancer PC-3M cell line. Interestingly, the chemistry of this particular Hemimycale species was never investigated.…”

Section: Introductionmentioning

confidence: 99%

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Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products

Mudit

Khanfar

Anbalagan

et al. 2009

Bioorganic & Medicinal Chemistry

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General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. a b s t r a c tThe Red Sea sponge Hemimycale arabica afforded the known (Z)-5-(4-hydroxybenzylidene)-hydantoin (1), (R)-5-(4-hydroxybenzyl)hydantoin (2), and (Z)-5-((6-bromo-1H-indol-3-yl)methylene)-hydantoin (3). The natural phenylmethylene hydantoin (PMH) 1 and the synthetic (Z)-5-(4-(ethylthio)benzylidene)-hydantoin (4) showed potent in vitro anti-growth and anti-invasive properties against PC-3M prostate cancer cells in MTT and spheroid disaggregation assays. PMHs 1 and 4 also showed significant anti-invasive activities in orthotopic xenograft and transgenic mice models. To study the effect of electronic and lipophilic parameters on the activity, a wide array of several substituted aldehydes possessing electron-withdrawing (+r), lipophilic (+p), electron-donating (Àr), and less lipophilic substituents (Àp) were used to synthesize several PMHs. Few des-phenylmethylenehydantoins and 2-thiohydanoins were also synthesized and the anti-invasive activities of all compounds were evaluated. Comparative molecular field analysis (CoMFA) was then used to study the 3D QSAR. Predictive 3D QSAR model with conventional r 2 and cross validated coefficient (q 2 ) values up to 0.910 and 0.651 were established. In conclusion, PMH is a novel antimetastatic lead class with potential to control metastatic prostate cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products

Mudit

Khanfar

Anbalagan

et al. 2009

Bioorganic & Medicinal Chemistry

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“…1 Members of this class include the series called ptilocaulins, [2][3][4][5] crambescins (crambines), [6][7][8][9] ptilomycalin A, crambescidins, [9][10][11][12][13][14][15] and batzelladines. [15][16][17] They were isolated separately from marine sponges belonging to the genera Batzella, Monanchora, Arenochalina, and Crambe (Order Poecilosclerida) and Ptilocaulis (Order Axinellida) and starfish Fromia monilis, and Celerina heffernani.…”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17] They were isolated separately from marine sponges belonging to the genera Batzella, Monanchora, Arenochalina, and Crambe (Order Poecilosclerida) and Ptilocaulis (Order Axinellida) and starfish Fromia monilis, and Celerina heffernani. 18 These metabolites display diverse biological activities including cytotoxicity against P388, L1210, HCT-16, KB cell lines, 2,[10][11][12]14 antifungal activity against Candida albicans, 10 antiviral activity against Herpes simplex virus type 1 (HSV-1), and Hepatitis-B virus [10][11][12][13] and potent calcium channel antagonist activity. 14 Batzelladine A and B were reported to inhibit the binding of HIV-gp 120 to the CD4 cell-surface receptor protein 16 and crambescidins 826, 800, and fromiamycalin inhibited HIV-envelope-mediated fusion and as a result are potential inhibitors of HIV.…”

Section: Introductionmentioning

confidence: 99%

Crystallographic and NMR Studies of Antiinfective Tricyclic Guanidine Alkaloids from the Sponge Monanchora unguifera

et al. 2005

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Three tricyclic guanidine alkaloids, including 1,8a;8b,3a-didehydro-8β-hydroxyptilocaulin (1), 1,8a;8b,3a-didehydro-8α-hydroxyptilocaulin (2) and mirabilin B (3), were identified from the marine sponge Monanchora unguifera. 1,8a;8b,3a-Didehydro-8α-hydroxyptilocaulin (2) is a new stereoisomer of 1, the structure of which was elucidated by spectroscopic analysis, comparison of its spectral data with those of 1, and confirmed by X-ray analysis. Compounds 1 and 2 cocrystallized in an unusual perfect order and packed around an approximate inversion center. A mixture of 1 and 2 is active against the malaria parasite Plasmodium falciparum with an IC 50 value of 3.8 μg/mL while mirabilin B (3) exhibited antifungal activity against Cryptococcus neoformans with an IC 50 value of 7.0 μg/mL and antiprotozoal activity against Leishmania donovani with an IC 50 value of 17 μg/mL.

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“…Among them, organocatalysts are especially attractive since they do not require strictly controlled reaction conditions, and are not considered to have much unfavorable environment effect compared to the metalcontaining catalysts. 4,5) We have recently developed the novel C 2 -symmetrical chiral cyclic guanidine compounds 1 as new organocatalysts, [6][7][8][9] whose structure was inspired by the marine guanidine alkaloid ptilomycalin A [10][11][12] and its analogs ( Fig. 1).…”

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confidence: 99%

Development of Novel Chiral Urea Catalysts for the Hetero-Michael Reaction

et al. 2004

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Michael addition to a,b-unsaturated carbonyl compounds is one of the fundamental bond-forming processes and offers an extremely powerful tool for the synthesis of highly functionalized organic molecules.1) Thus, development of efficient chiral catalysts for this reaction is still an exciting topic in synthetic organic chemistry.2,3) Various types of catalysts have been developed so far. Among them, organocatalysts are especially attractive since they do not require strictly controlled reaction conditions, and are not considered to have much unfavorable environment effect compared to the metalcontaining catalysts. 4,5) We have recently developed the novel C 2 -symmetrical chiral cyclic guanidine compounds 1 as new organocatalysts, 6-9) whose structure was inspired by the marine guanidine alkaloid ptilomycalin A 10-12) and its analogs (Fig. 1). 13,14) These catalysts were found to accelerate the heteroMichael reaction depending upon their cavity size. 7) One of the catalyst 1b works as phase-transfer catalyst for the alkylation of Schiff base imine with high enantioselectivity.8) Although 1 possesses wide possibility to be developed as superior organocatalyst, it also have some deficiencies, i.e., requirement for relatively long steps preparation, and no asymmetric induction at the hetero-Michael reaction.7) To overcome these issues, we focused our attention on urea and/or thiourea compounds, which can be grasped as core structure of 1, as prototype of new efficient and practical organocatalysts. Herein we wish to report the preliminary/basic results of a novel urea-type catalyst 10 for the hetero-Michael reaction, including results on an asymmetric version of this conjugate addition reaction. Results and DiscussionUrea and thiourea groups are known to coordinate to a carbonyl group as guanidine group, and to activate it by lowering the LUMO energy via partial protonation. Thus, various carbonyl group reactions catalyzed by urea or thiourea compounds have been developed. [15][16][17][18][19][20][21][22] At the outset of our studies for developing new chiral urea and/or thiourea catalyst of the hetero-Micahel reaction, we investigated the reaction of pyrrolidine (2) with g-crotonolactone (3) in the presence of the simple ureas 5 and 7, 17) thioureas 6 and 8, 17) and guanidine 9 as catalysts (Fig. 2).These reactions were performed under Mendoza's conditions, [23][24][25][26] i.e., the ratio of 2, 3 and catalyst was 1 : 1 : 0.1, and the concentrations of the substrate 2 and 3 were set at 0.3 M in CDCl 3 . The accelerating activities of the catalysts for this hetero-Michael reaction were determined by measuring the t 1/2 (monitored by 1 H-NMR), and the results are summarized in Table 1.The urea 5 and thiourea 6 accelerated this conjugate addition reaction 3.0 and 2.6-fold, respectively, over the uncatalyzed reaction as expected. From the consideration of the reaction mechanism (vide infra), introduction of EWGs on the aromatic rings of 5 and/or 6 was expected to increase their catalytic activity. In fact, catalysts 7 ...

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Ptilomycalin A: a novel polycyclic guanidine alkaloid of marine origin

Cited by 169 publications

References 1 publication

Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products

Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products

Crystallographic and NMR Studies of Antiinfective Tricyclic Guanidine Alkaloids from the Sponge Monanchora unguifera

Development of Novel Chiral Urea Catalysts for the Hetero-Michael Reaction

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