Synthesis and Cytotoxicity of Novel Sansalvamide A Derivatives

Carroll, Chris L.; Johnston, Jennifer V. C.; Kekec, Ahmet; Brown, Julia; Parry, Emily; Cajica, Julia; Medina, Irene García; Cook, Kristina M.; Corral, Ricardo S.; Pan, Po-Shen; McAlpine, Shelli R.

doi:10.1021/ol0517325

Cited by 6 publications

(9 citation statements)

References 1 publication

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“…The identified sum formula of C 32 H 51 O 5 N 5 , from 1DF9 cosmid (RVA14), fits well with the structure of a cyclic pentapeptide. Interestingly, an identical sum formula is found in sansalvamide A peptides (22)(23)(24), synthetic derivatives of the depsipeptide natural product sansalvamide A that were isolated from a marine fungus and showed potent anti-cancer activity (25). Isolation of all identified compounds for detailed structure elucidation is currently underway.…”

Section: Resultsmentioning

confidence: 89%

Rapid Virulence Annotation (RVA): Identification of virulence factors using a bacterial genome library and multiple invertebrate hosts

Waterfield

Sánchez-Contreras

Eleftherianos

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Current sequence databases now contain numerous whole genome sequences of pathogenic bacteria. However, many of the predicted genes lack any functional annotation. We describe an assumption-free approach, Rapid Virulence Annotation (RVA), for the high-throughput parallel screening of genomic libraries against four different taxa: insects, nematodes, amoeba, and mammalian macrophages. These hosts represent different aspects of both the vertebrate and invertebrate immune system. Here, we apply RVA to the emerging human pathogen Photorhabdus asymbiotica using “gain of toxicity” assays of recombinant Escherichia coli clones. We describe a wealth of potential virulence loci and attribute biological function to several putative genomic islands, which may then be further characterized using conventional molecular techniques. The application of RVA to other pathogen genomes promises to ascribe biological function to otherwise uncharacterized virulence genes.

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Section: Resultsmentioning

confidence: 89%

Rapid Virulence Annotation (RVA): Identification of virulence factors using a bacterial genome library and multiple invertebrate hosts

Waterfield

Sánchez-Contreras

Eleftherianos

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…The amine was deprotected on fragment 1 using TFA and the acid was revealed in fragment 2 using lithium hydroxide. Fragment 1 and fragment 2 were coupled using multiple coupling agents, ,– yielding 75 examples of linear pentapeptides (66–90% yield) . In the case of the di- and tripeptide construction, acid/base workup removed excess reagents and side products, and the NMR indicated compounds did not require further purification.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Study of Sansalvamide A Derivatives and their Structure–Activity Relationships against Drug-Resistant Colon Cancer Cell Lines

et al. 2008

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We report an extensive structure-activity relationship (SAR) of 62 compounds active against two drug-resistant colon cancer cell lines. Our comprehensive evaluation of two generations of compounds utilizes SAR, NMR, and molecular modeling to evaluate the key 3D features of potent compounds. Of the seven most potent compounds reported here, five are second-generation, emphasizing our ability to incorporate potent features found in the first generation and utilize their structures to design potency into the second generation. These analogs share no structural homology to current colon cancer drugs, are cytotoxic at levels on par with existing drugs treating other cancers, and demonstrate selectivity for drug-resistant colon cancer cell lines over noncancerous cell lines. Thus, we have established sansalvamide A as an excellent lead for treating multiple drug-resistant colon cancers.

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“…A number of analogs have been made. These sansalvamide A derivatives [6][7][8][9][10][14][15][16][17][18][19][20] have shown that they are privileged structures and exhibit potency against multiple targets in numerous cancer cell lines. The examples of potent cytotoxicity against pancreatic, colon, breast, prostate and melanoma cancers clearly indicate the potential of this compound class as a platform useful in targeting these cancers.…”

Section: Biological Activitymentioning

confidence: 99%

“…To evaluate their anticancer activities in vitro, we used the drug-resistant human cancer cell line HCT-116. [6][7][8][9][10] RESULTS AND DISCUSSION Structural elucidation Compound 1 was obtained as a colorless oil with the UV absorptions at l max of 232 and 275 nm. The molecular formula of 1 was established as C 40 H 51 N 5 O 5 on the basis of HRESI-MS and NMR analysis, which indicated the presence of 18 degrees of unsaturation.…”

Section: Introductionmentioning

confidence: 99%

Bingchamides A and B, two novel cyclic pentapeptides from the Streptomyces bingchenggensis: fermentation, isolation, structure elucidation and biological properties

Xiang

Wang

et al. 2009

J Antibiot

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Two novel cyclic pentapeptides, bingchamides A (1) and B (2), have been isolated from the organic extracts of the mycelium of Streptomyces bingchenggensis. The structures of 1 and 2 were elucidated on the basis of extensive 1D and 2D NMR, as well as HRESI-MS, electrospray ionization-MS, UV and IR spectroscopic data analysis. Bingchamides A (1) and B (2) exhibited in vitro cytotoxicity toward human colon carcinoma cell line HCT-116 with the IC 50 values of 14.1 and 18.0 lg ml À1 , respectively. The bingchamides A (1) and B (2) scaffolds are probably promising structures for the development of new antitumor agents.

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Synthesis and Cytotoxicity of Novel Sansalvamide A Derivatives

Cited by 6 publications

References 1 publication

Rapid Virulence Annotation (RVA): Identification of virulence factors using a bacterial genome library and multiple invertebrate hosts

Rapid Virulence Annotation (RVA): Identification of virulence factors using a bacterial genome library and multiple invertebrate hosts

Comprehensive Study of Sansalvamide A Derivatives and their Structure–Activity Relationships against Drug-Resistant Colon Cancer Cell Lines

Bingchamides A and B, two novel cyclic pentapeptides from the Streptomyces bingchenggensis: fermentation, isolation, structure elucidation and biological properties

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