Modeling the Preferred Shapes of Polyamine Transporter Ligands and Dihydromotuporamine-C Mimics:  Shovel versus Hoe.

Breitbeil, Fred W.; Kaur, Navdeep; Delcros, Jean‐Guy; Martin, Bénédicte; Abboud, Khalil A.; Phanstiel,

doi:10.1021/jm070181g

Cited by 7 publications

(15 citation statements)

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“…Williams et al also showed that the degrees of unsaturation in the ring dramatically affected the biological activity of the series, where a saturated ring proved to be the most potent design in terms of antimigration properties . Work by our group also demonstrated that anthryl ring based mimics ( 5a and 5b ) could reproduce the cytotoxic effects of 4a but not its antimetastatic properties …”

Section: Introductionmentioning

confidence: 88%

Synthesis and Biological Evaluation of Antimetastatic Agents Predicated upon Dihydromotuporamine C and Its Carbocyclic Derivatives

et al. 2014

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The motuporamines isolated from the sea sponge Xestospongia exigua are of biological interest because of their unique antimigration and antiangiogenic properties. Key bioactive features were found to be a saturated 15-membered heterocycle and a norspermidine motif. This paper describes new analogues that modulate the cytotoxicity of this compound class and have enhanced antimigration properties. By movement of the polyamine chain outside the ring, new carbocycles were discovered that doubled the antimigration potency and reduced compound toxicity by 133-fold. Mice injected with metastatic human L3.6pl pancreatic cancer cells demonstrated significant reduction in liver metastases when treated with N(1)-(3-aminopropyl)-N(3)-(cyclopentadecylmethyl)propane-1,3-diamine compared with dihydromotuporamine C. Significant changes in specific ceramide populations (N16:0 and N22:1) were noted in L3.6pl cells treated with dihydromotuporamine C but not for the cyclopentadecylmethylnorspermidine derivative, which had lower toxicity. Both compounds gave increased levels of specific low molecular weight sphingomyelins, suggesting that they may act upon sphingomyelin processing enzymes.

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Section: Introductionmentioning

confidence: 88%

Synthesis and Biological Evaluation of Antimetastatic Agents Predicated upon Dihydromotuporamine C and Its Carbocyclic Derivatives

et al. 2014

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“…15 As such, we adopted a strategy that utilized the preformed macrocycle 5a. Our group also developed a multistep pathway for synthesis of the parent compound 1 16,17 and used ketone 5a and Boc-protected polyamines to make carbocyclic derivatives. 12 This latter approach was facilitated by initial conversion of the ketone to its corresponding alkene followed by anti-Markovnikov addition of borane to give after workup the primary alcohol 5b.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Indeed, modulation within the polyamine message itself and the distance between the polyamine message and the macrocycle did not improve PTS targeting in this homologous series. For example, we noted that the polyamine message 4b, when appended to the anthracene substituent (17), was able to accomplish modest PTS targeting (CHO-MG/CHO IC 50 ratio 5.8) while the related macrocyclecontaining compound 3a did not (CHO-MG/CHO IC 50 ratio 0.9).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Synthesis and Bioevaluation of Macrocycle–Polyamine Conjugates as Cell Migration Inhibitors

2017

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The motuporamines are natural products isolated from the New Guinea sea sponge Xestospongia exigua. Dihydromotuporamine C contains a large macrocycle and an appended polyamine component and was shown to be both antimetastatic and cytotoxic to human L3.6pl pancreatic cancer cells. A series of macrocycle-polyamine conjugates were prepared, and the sequence of the polyamine component was varied to optimize the antimigration properties (as measured in L3.6pl cells) of this molecular class. A one-carbon spacer between the 15-membered carbocycle and the appended polyamine showed improved antimigration properties. A survey of different polyamine sequences containing two, three, or four carbon spacers revealed that the natural polyamine sequence (norspermidine, a 3,3-triamine) was superior in terms of inhibiting the migration of L3.6pl cells in vitro. An investigation of the respective ceramide and sphingomyelin populations in L3.6pl cells revealed that these molecules can modulate both ceramide and sphingomyelin pools in cells and inhibit cell migration.

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“…It is also noteworthy that non-natural motuporamine derivatives were recently prepared and are now widely studied for their interesting anti-angiogenic and antimicrobial activities. [190][191][192][193][194][195] V-Polyamines from microorganisms…”

Section: Iv-2-3 Motuporaminesmentioning

confidence: 99%

Synthesis and Biological Activities of Naturally Functionalized Polyamines: An Overview

Negrel

Brunel

2021

CMC

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Modeling the Preferred Shapes of Polyamine Transporter Ligands and Dihydromotuporamine-C Mimics: Shovel versus Hoe.

Cited by 7 publications

References 0 publications

Synthesis and Biological Evaluation of Antimetastatic Agents Predicated upon Dihydromotuporamine C and Its Carbocyclic Derivatives

Synthesis and Biological Evaluation of Antimetastatic Agents Predicated upon Dihydromotuporamine C and Its Carbocyclic Derivatives

Synthesis and Bioevaluation of Macrocycle–Polyamine Conjugates as Cell Migration Inhibitors

Synthesis and Biological Activities of Naturally Functionalized Polyamines: An Overview

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