Chemistry of renieramycins. Part 8: Synthesis and cytotoxicity evaluation of renieramycin M–jorunnamycin A analogues

Charupant, Kornvika; Daikuhara, Naomi; Saito, Emi; Amnuoypol, Surattana; Suwanborirux, Khanit; Owa, Takashi; Saito, Naoki

doi:10.1016/j.bmc.2009.05.009

Cited by 43 publications

(54 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We realized the gram-scale supply of renieramycin-type compounds using our procedure, and recently reported significant results gained from the extension of our initial investigation and the results of cytotoxicity evaluation of C-22 ester analogues and a very promising compound, the 2′-pyridinecarboxylic acid ester derivative [19] (Figure 2). We also reported the isolation of jorunnamycins A–C from the mantles, visceral organs, and egg ribbons of the Thai nudibranch Jorunna funebris, following the same procedure that used potassium cyanide [20].…”

Section: Introductionmentioning

confidence: 99%

Microarray-Based Transcriptional Profiling of Renieramycin M and Jorunnamycin C, Isolated from Thai Marine Organisms

et al. 2009

Self Cite

View full text Add to dashboard Cite

Renieramycin M and jorunnamycin C, two isoquinolinequinone compounds differing only at the C-22 ester side chain, were evaluated for their cytotoxic effects on human colon (HCT116) and breast (MDA-MB-435) cancer cell lines. These two compounds displayed potent cancer cell growth inhibition, their IC50 values reaching nanomolar order. To examine their effects on transcription, we carried out oligonucleotide microarray analysis with focus on the similarities and differences between the two compounds in terms of transcriptional profiles. We found that the down-regulation of PTPRK (protein tyrosine phosphatase receptor type K) can be considered as a biomarker responsive to the cytotoxic effects of this class of antitumor marine natural products.

show abstract

Section: Introductionmentioning

confidence: 99%

Microarray-Based Transcriptional Profiling of Renieramycin M and Jorunnamycin C, Isolated from Thai Marine Organisms

et al. 2009

Self Cite

View full text Add to dashboard Cite

show abstract

“…The isolation, purification, chemical synthesis, and evaluation of cytotoxicity of renieramycin M (RM, the compound 2a), ecteinascidin-770 (ET-770, the compound 1a), and a 2’ -N -4”-pyridinecarbonyl derivative of ET-770, the compound 3 were previously described in detail [10-15]. The chemical structures of these compounds are shown in Figure 1.…”

Section: Methodsmentioning

confidence: 99%

Molecular network profiling of U373MG human glioblastoma cells following induction of apoptosis by novel marine-derived anti-cancer 1,2,3,4-tetrahydroisoquinoline alkaloids

et al. 2012

Self Cite

View full text Add to dashboard Cite

BackgroundGlioblastoma is the most aggressive form of brain tumors showing resistance to treatment with various chemotherapeutic agents. The most effective way to eradicate glioblastoma requires the concurrent inhibition of multiple signaling pathways and target molecules involved in the progression of glioblastoma. Recently, we obtained a series of 1,2,3,4-tetrahydroisoquinoline alkaloids with potent anti-cancer activities, including ecteinascidin-770 (ET-770; the compound 1a) and renieramycin M (RM; the compound 2a) from Thai marine invertebrates, together with a 2’-N-4”-pyridinecarbonyl derivative of ET-770 (the compound 3). We attempted to characterize the molecular pathways responsible for cytotoxic effects of these compounds on a human glioblastoma cell line U373MG.MethodsWe studied the genome-wide gene expression profile on microarrays and molecular networks by using pathway analysis tools of bioinformatics.ResultsAll of these compounds induced apoptosis of U373MG cells at nanomolar concentrations. The compound 3 reduced the expression of 417 genes and elevated the levels of 84 genes, while ET-770 downregulated 426 genes and upregulated 45 genes. RM decreased the expression of 274 genes and increased the expression of 9 genes. The set of 196 downregulated genes and 6 upregulated genes showed an overlap among all the compounds, suggesting an existence of the common pathways involved in induction of apoptosis. We identified the ErbB (EGFR) signaling pathway as one of the common pathways enriched in the set of downregulated genes, composed of PTK2, AKT3, and GSK3B serving as key molecules that regulate cell movement and the nervous system development. Furthermore, a GSK3B-specific inhibitor induced apoptosis of U373MG cells, supporting an anti-apoptotic role of GSK3B.ConclusionMolecular network analysis is a useful approach not only to characterize the glioma-relevant pathways but also to identify the network-based effective drug targets.

show abstract

“…To date, five total syntheses of renieramycin G [15][16][17][18][19][20][21] and four total syntheses of cribrostatin 4 22-25) have been published. Several studies on the SAR of renieramycins, including renieramycin G and cribrostatin 4, were conducted, 8,[26][27][28][29][30] but the cytotoxicity profiles of these compounds were not addressed.Among a handful of studies of simple models containing a lactam ring, such as 3, Ong and coworkers reported that pentacyclic scaffold 4 showed low cytotoxicity.31,32) Avendaño and coworkers discovered that pyrazino[1.2-b] isoquinoline-4-one derivative 5 induced apoptosis from the G2/M phase of the cell cycle without causing DNA damage.33) These findings have stirred much excitement and inspired the search for other simplified tetrahydroisoquinolines having antitumor activities that are similar to or more potent than those displayed by parRegular Article …”

mentioning

confidence: 99%

“…by pretreatment with potassium cyanide. 6,7) Structure-activity relationship (SAR) investigations of a variety of derivatives of renieramycin M [8][9][10] yielded several pieces of evidence pointing to the fact that virtually all biologically active members of this family of natural products, such as 1, possess a carbinolamine or cyano function at C-21, which permits the formation of potent electrophilic iminium ion species 2, a compound that has been implicated in the formation of covalent bonds with DNA and possibly other bio macromolecules (Fig. 2).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Preparation of Tricyclic Lactam Model Compounds of Renieramycin and Saframycin Anticancer Natural Products from Common Intermediate

Nakai

Yokoya

Saito

2013

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

Tricyclic lactam model compounds of the left half (ABC ring) of renieramycin and saframycin anticancer natural products were prepared from common intermediate 6a. Readily available alcohol 6a was converted into enamide 8, and this was followed by transformation into 6b through a hydrobromination reaction in a stereoselective manner. Some diastereomers at C-6 to C-11a of the tricyclic lactam model compounds having several functional groups at C-6 were prepared from 6a or 6b in good yields. We presented also an unexpected reductive acetylation of the p-quinone to produce the corresponding 3,4-dehydro derivative.Key words renieramycin; saframycin; tetrahydroisoquinoline; hydrobromination; preparation; reductive acylation Tetrahydroisoquinoline natural products, including renieramycins, saframycins, ecteinascidins, naphthyridinomycins, and quinocarcins, have persistently attracted considerable interest for more than 30 years due to their novel structures and meager availability in nature, as well as their potent antitumor activity 1,2) ( Fig. 1). Ecteinascidin 743, in particular, has received considerable attention for its strong in vivo activity.3)It is currently marketed in over fifty countries for the treatment of soft-tissue sarcoma and phase II/III clinical trials for the treatment of other cancers are ongoing. 4,5) In the course of our research of new metabolites from marine animals, we isolated renieramycin M in gram scale from the Thai blue sponge Xestospongia sp. by pretreatment with potassium cyanide.6,7) Structure-activity relationship (SAR) investigations of a variety of derivatives of renieramycin M 8-10) yielded several pieces of evidence pointing to the fact that virtually all biologically active members of this family of natural products, such as 1, possess a carbinolamine or cyano function at C-21, which permits the formation of potent electrophilic iminium ion species 2, a compound that has been implicated in the formation of covalent bonds with DNA and possibly other bio macromolecules (Fig. 2). We are also very interested in the biological activities of renieramycin G 11) and cribrostatin 4 (=renieramycin H [12][13][14] ) because both compounds show antiproliferative activity. Renieramycin G and cribrostatin 4 are tetrahydroisoquinolines possessing a C-21 lactam carbonyl group; however, they exhibit low cytotoxicity and are less active than their respective C-21 cyano or carbinolamine containing relatives. To date, five total syntheses of renieramycin G [15][16][17][18][19][20][21] and four total syntheses of cribrostatin 4 22-25) have been published. Several studies on the SAR of renieramycins, including renieramycin G and cribrostatin 4, were conducted, 8,[26][27][28][29][30] but the cytotoxicity profiles of these compounds were not addressed.Among a handful of studies of simple models containing a lactam ring, such as 3, Ong and coworkers reported that pentacyclic scaffold 4 showed low cytotoxicity.31,32) Avendaño and coworkers discovered that pyrazino[1.2-b] isoquinoline-4-one derivative 5 in...

show abstract

Chemistry of renieramycins. Part 8: Synthesis and cytotoxicity evaluation of renieramycin M–jorunnamycin A analogues

Cited by 43 publications

References 32 publications

Microarray-Based Transcriptional Profiling of Renieramycin M and Jorunnamycin C, Isolated from Thai Marine Organisms

Microarray-Based Transcriptional Profiling of Renieramycin M and Jorunnamycin C, Isolated from Thai Marine Organisms

Molecular network profiling of U373MG human glioblastoma cells following induction of apoptosis by novel marine-derived anti-cancer 1,2,3,4-tetrahydroisoquinoline alkaloids

Preparation of Tricyclic Lactam Model Compounds of Renieramycin and Saframycin Anticancer Natural Products from Common Intermediate

Contact Info

Product

Resources

About