Total synthesis and biological evaluation of tambjamine K and a library of unnatural analogs

Aldrich, Leslie N.; Stoops, Sydney L.; Crews, Brenda C.; Marnett, Lawrence J.; Lindsley, Craig W.

doi:10.1016/j.bmcl.2010.06.154

Cited by 37 publications

(38 citation statements)

References 16 publications

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“…23 This surprising result led us to study 7 in our standard HCT116 colon carcinoma cell viability assay. 22-24 Here as well, 7 had no affect on HCT116 cell viability after 48 hours. In contrast, advanced intermediate 21 , an unnatural analog of 7 , displayed an IC 50 of 3 μM in this assay, completely killing the cells after 48 hours.…”

mentioning

confidence: 84%

Total Synthesis of (+)-7-Bromotrypargine and Unnatural Analogues: Biological Evaluation Uncovers Activity at CNS Targets of Therapeutic Relevance

Brogan

Stoops

Crews

et al. 2011

ACS Chem. Neurosci.

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The first total synthesis of (+)-7-bromotrypargine, a β-carboline alkaloid from Ancornia sp. is reported. The synthesis proceeds in 9 steps, 8 steps longest linear sequence, in 36.9% overall yield. Biological characterization found that (+)-7-bromotrypargine is an H3 antagonist, and a selective inhibitor of DAT and NET, without inhibiting SERT. Moreover, unlike electron rich congeners, (+)-7-bromotrypargine is not cytotoxic, and thus represents an attractive starting point for chemical optimization; therefore, we piloted a number of chemistries for the synthesis of unnatural analogs.

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mentioning

confidence: 84%

Total Synthesis of (+)-7-Bromotrypargine and Unnatural Analogues: Biological Evaluation Uncovers Activity at CNS Targets of Therapeutic Relevance

Brogan

Stoops

Crews

et al. 2011

ACS Chem. Neurosci.

Self Cite

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“…Tambjamines are methoxypyrrolic alkaloids whose chemical features resemble the bacterial prodigiosins . All these compounds contain a common 4‐methoxy‐2,2’‐bipyrrole chromophore . Tambjamines A–D (tambjamine D; 78a ; Fig.…”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

“…Tambjamines E ( 78b ; Fig. ; Table ), F, G, H, I and J were isolated from various bacteria and marine invertebrates . Tambjamine K ( 78c ; Fig.…”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Ciavatta

Lefranc

Carbone

et al. 2016

Medicinal Research Reviews

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The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity.

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“…Compounds in both families possess a bipyrrole core that interacts with biologically relevant ions, from which most of their bioactive properties emerge . The structural variation found in members of these families, such as macrocyclization and halogenation, alters the potency and specificity of their bioactivities . For this reason many studies have concentrated on chemical synthesis of analogues; however, the native bacterial producers have already evolved a simple biosynthetic mechanism to allow for straightforward generation of structural diversity …”

Section: Introductionmentioning

confidence: 99%

Purification and Kinetic Characterization of the Essential Condensation Enzymes Involved in Prodiginine and Tambjamine Biosynthesis

et al. 2019

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Prodiginines and tambjamines are related families of bioactive alkaloid natural products with pharmaceutical potential. Both compound families result from a convergent biosynthetic pathway ending in the condensation of a conserved bipyrrole core with a variable partner. This reaction is performed by unique condensation enzymes, and has the potential to be manipulated to produce new pyrrolic compounds. We have purified and reconstituted the in vitro activity of the condensation enzymes PigC and TamQ from Pseudoalteromonas sp., which are involved, respectively, in the prodiginine and tambjamine biosynthetic pathways. Kinetic analysis confirmed a Uni Uni Bi Uni ping‐pong reaction sequence with competitive and uncompetitive substrate inhibition for PigC and TamQ respectively. The kinetic parameters of each enzyme provide insight into their differing substrate scope, and suggest that TamQ may have evolved a wide substrate tolerance that can be used for the production of novel prodiginines and tambjamines.

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Total synthesis and biological evaluation of tambjamine K and a library of unnatural analogs

Cited by 37 publications

References 16 publications

Total Synthesis of (+)-7-Bromotrypargine and Unnatural Analogues: Biological Evaluation Uncovers Activity at CNS Targets of Therapeutic Relevance

Total Synthesis of (+)-7-Bromotrypargine and Unnatural Analogues: Biological Evaluation Uncovers Activity at CNS Targets of Therapeutic Relevance

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Purification and Kinetic Characterization of the Essential Condensation Enzymes Involved in Prodiginine and Tambjamine Biosynthesis

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