Rigidins B−D, New Pyrrolopyrimidine Alkaloids from a Tunicate <i>Cystodytes</i> Species

Tsuda, Masashi; Nozawa, Kohei; Shimbo, Kazutaka; Kobayashi, Jun’ichi

doi:10.1021/np020393a

Cited by 35 publications

(24 citation statements)

References 6 publications

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“…10-12 The first general total synthesis of rigidins A, B, C and D, which involved only four steps from commercially available materials, was reported by the authors in 2011 13 and allowed for a thorough investigation of their biological properties. However, despite the earlier reports of promising antiproliferative activity against murine leukemia L1210 cells, 11 the rigidins were found to have very little, if any, activity against cultured human cancer cells. 14 Further synthetic investigations led to the development of approaches allowing for the modification of the 7-deazaxanthine skeleton present in the rigidins to obtain the corresponding 7-deazahypoxanthine ( A ), 7-deazaadenine ( B ) and 7-deazapurine ( C ) frameworks (Figure 1).…”

Section: Introductionmentioning

confidence: 77%

Synthetic and Biological Studies of Tubulin Targeting C2‐Substituted 7‐Deazahypoxanthines Derived from Marine Alkaloid Rigidins

et al. 2014

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C2-aryl- and C2-alkyl-7-deazahypoxanthines as analogues of marine alkaloid rigidins were prepared utilizing novel synthetic methods developed for the construction of the pyrrolo[2,3-d]pyrimidine ring system. The new compounds exhibited submicromolar to nanomolar antiproliferative potencies against a panel of cell lines including in vitro models for drug resistant tumors, such as glioblastoma, melanoma and non-small-cell lung cancer. A selected representative C2-methyl-7-deazahypoxanthine was found to inhibit microtubule dynamics in cancer cells, lending evidence for tubulin targeting as a mode of action for these compounds in cancer cells. The results of the docking studies utilizing the colchicine site on β-tubulin were consistent with the observed SAR data, including an important finding that derivatization at C2 with long alkyl groups leads to the retention of activity, thus permitting the attachment of a biotin-containing linker for the subsequent proteomics assays. Because many microtubule-targeting compounds are successfully used to fight cancer in the clinic, the reported antitubulin rigidin analogues have significant potential as new anticancer agents.

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Section: Introductionmentioning

confidence: 77%

Synthetic and Biological Studies of Tubulin Targeting C2‐Substituted 7‐Deazahypoxanthines Derived from Marine Alkaloid Rigidins

et al. 2014

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“…Preliminary biological results showed that at 10 μg/mL, compounds 4–6 inhibited leukemia tumor cell growth by 40%, 40% and 20% respectively [11]. …”

Section: Resultsmentioning

confidence: 99%

Rigidin E, a New Pyrrolopyrimidine Alkaloid from a Papua New Guinea Tunicate Eudistoma Species

et al. 2003

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“…This compound exhibited antagonistic activity against calmodulin. The biological activities of the related compounds, rigidin B ( 29 ), C ( 30 ) and D ( 31 ), which were isolated from a different species of tunicate, Cystodytes sp., are yet to be determined [34]. …”

Section: Simple Dehydrotyrosine Derivatives: Tuberine Erbastatinmentioning

confidence: 99%

Bioactive Dehydrotyrosyl and Dehydrodopyl Compounds of Marine Origin

Sugumaran

Robinson

2010

Marine Drugs

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The amino acid, tyrosine, and its hydroxylated product, 3,4-dihydroxyphenylalanine (dopa), plays an important role in the biogenesis of a number of potentially important bioactive molecules in marine organisms. Interestingly, several of these tyrosyl and dopa-containing compounds possess dehydro groups in their side chains. Examples span the range from simple dehydrotyrosine and dehydrodopamines to complex metabolic products, including peptides and polycyclic alkaloids. Based on structural information, these compounds can be subdivided into five categories: (a) Simple dehydrotyrosine and dehydrotyramine containing molecules; (b) simple dehydrodopa derivatives; (c) peptidyl dehydrotyrosine and dehydrodopa derivatives; (d) multiple dehydrodopa containing compounds; and (e) polycyclic condensed dehydrodopa derivatives. These molecules possess a wide range of biological activities that include (but are not limited to) antitumor activity, antibiotic activity, cytotoxicity, antioxidant activity, multidrug resistance reversal, cell division inhibition, immunomodulatory activity, HIV-integrase inhibition, anti-viral, and anti-feeding (or feeding deterrent) activity. This review summarizes the structure, distribution, possible biosynthetic origin, and biological activity, of the five categories of dehydrotyrosine and dehydrodopa containing compounds.

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Rigidins B−D, New Pyrrolopyrimidine Alkaloids from a Tunicate Cystodytes Species

Abstract: Three new pyrrolopyrimidine alkaloids, rigidins B-D (1-3), have been isolated from an Okinawan marine tunicate Cystodytes sp., and the structures were elucidated on the basis of spectroscopic data.

Cited by 35 publications

References 6 publications

Synthetic and Biological Studies of Tubulin Targeting C2‐Substituted 7‐Deazahypoxanthines Derived from Marine Alkaloid Rigidins

Synthetic and Biological Studies of Tubulin Targeting C2‐Substituted 7‐Deazahypoxanthines Derived from Marine Alkaloid Rigidins

Rigidin E, a New Pyrrolopyrimidine Alkaloid from a Papua New Guinea Tunicate Eudistoma Species

Bioactive Dehydrotyrosyl and Dehydrodopyl Compounds of Marine Origin

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