Chemistry of renieramycins. Part 13: Isolation and structure of stabilized renieramycin type derivatives, renieramycins W–Y, from Philippine blue sponge Xestospongia sp., pretreated with potassium cyanide

Tatsukawa, Mari; Punzalan, Louvy Lynn; Magpantay, Hilbert D.; Villaseñor, Irene M.; Concepción, Gisela P.; Suwanborirux, Khanit; Yokoya, Masashi; Saito, Naoki

doi:10.1016/j.tet.2012.06.067

Cited by 27 publications

(28 citation statements)

References 27 publications

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“…One of the marine-derived natural products is renieramycins. Renieramycins are alkaloids in the tetrahydroisoquinoline family [28], which is derived from various marine organisms, including sponges in the genera Reniera [29,30], Xestospongia [31,32,33,34,35], Cribrochalina [36,37], and Neopetrosia [38]. However, they are unstable and decomposed after extraction and isolation.…”

Section: Introductionmentioning

confidence: 99%

Renieramycin T Induces Lung Cancer Cell Apoptosis by Targeting Mcl-1 Degradation: A New Insight in the Mechanism of Action

et al. 2019

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Among malignancies, lung cancer is the major cause of cancer death. Despite the advance in lung cancer therapy, the five-year survival rate is extremely restricted due to therapeutic failure and disease relapse. Targeted therapies selectively inhibiting certain molecules in cancer cells have been accepted as promising ways to control cancer. In lung cancer, evidence has suggested that the myeloid cell leukemia 1 (Mcl-1) protein, an anti-apoptotic member of the Bcl-2 family, is a target for drug action. Herein, we report the Mcl-1 targeting activity of renieramycin T (RT), a marine-derived tetrahydroisoquinoline alkaloid that was isolated from the Thai blue sponge Xestospongia sp. RT was shown to be dominantly toxic to lung cancer cells compared to the normal cells in the lung. The cytotoxicity of this compound toward lung cancer cells was mainly exerted through apoptosis induction. For the mechanism of action, we found that RT mediated activation of p53 protein and caspase-9 and -3 activations. While others Bcl-2 family proteins (Bcl-2, Bak, and Bax) were minimally changed in response to RT, Mcl-1 protein was dramatically diminished. We further performed the cycloheximide experiment and found that the half-life of Mcl-1 was significantly shortened by RT treatment. When MG132, a potent selective proteasome inhibitor, was utilized, it could restore the Mcl-1 level. Furthermore, immunoprecipitation analysis revealed that RT significantly increased the formation of Mcl-1-ubiquitin complex compared to the non-treated control. In conclusion, we report the potential apoptosis induction of RT with a mechanism of action involving the targeting of Mcl-1 for ubiquitin-proteasomal degradation. As Mcl-1 is critical for cancer cell survival and chemotherapeutic failure, this novel information regarding the Mcl-1-targeted compound would be beneficial for the development of efficient anti-cancer strategies or targeted therapies.

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Section: Introductionmentioning

confidence: 99%

Renieramycin T Induces Lung Cancer Cell Apoptosis by Targeting Mcl-1 Degradation: A New Insight in the Mechanism of Action

et al. 2019

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“…Natural products belonging to the bis -1,2,3,4-tetrahydroisoquinoline family, such as renieramycins, saframycins, and ecteinascidins, have attracted considerable attention due to their potent biological activities, structural diversity, and meager availability in nature (Figure 1) [1]. We have discovered a number of renieramycin marine natural products having extraordinary structures from blue sponges collected in Thailand and the Philippines [2,3,4]. For example, renieramycin M ( 1m ) isolated from the Thai blue sponge Xestospongia sp.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, renieramycins T ( 1t ) and U ( 1u ) share a common A-ring with ecteinascidin 743 (ET-743, 2 ), which has already been approved as an anticancer agent [3]. In addition, the A-ring of renieramycin Y ( 1y ) has the same substituent pattern as the E-ring of 2 [4]. These renieramycins have similar structures to 2 and are expected to have similar potent antitumor activity.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Synthesis and Cytotoxicity Evaluation of Right-Half Models of Antitumor Renieramycin Marine Natural Products

et al. 2018

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A general protocol for the asymmetric synthesis of 3-N-arylmethylated right-half model compounds of renieramycins was developed, which enabled structure–activity relationship (SAR) study of several 3-N-arylmethyl derivatives. The most active compound (6a) showed significant cytotoxic activity against human prostate cancer DU145 and colorectal cancer HCT116 cell lines (IC50 = 11.9, and 12.5 nM, respectively).

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“…We also elucidated the chemical structure of renieramycin T ( 1 c ), which was isolated from the blue sponge Xestospongia sp. in Thailand and the Philippines . Renieramycin T ( 1 c ) possesses a highly substituted phenol in the terminal A ring and a condensed 1,3‐dioxole ring, which are exactly the same as those in ecteinascidins.…”

Section: Introductionmentioning

confidence: 99%

Construction of the Pentacyclic Core and Formal Total Synthesis of (rac)‐Renieramycin T

Kimura

Saito

2018

ChemistryOpen

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A formal total synthesis of the antitumor marine natural product (rac)‐renieramycin T, which possesses a characteristic ecteinascidin‐type A ring in the renieramycin–saframycin core skeleton, was elaborated. The key steps in the synthesis of (rac)‐renieramycin T are a modified Pictet–Spengler cyclization of dialkylated oxomalonate derivatives and decarboxylation via a monocarboxylic acid derivative followed by stereocontrolled protonation of the enol intermediate. A key intermediate in our previous synthesis of renieramycin T was used, and the formal synthesis was accomplished in 21 steps from a known piperazine‐2,5‐dione derivative.

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Chemistry of renieramycins. Part 13: Isolation and structure of stabilized renieramycin type derivatives, renieramycins W–Y, from Philippine blue sponge Xestospongia sp., pretreated with potassium cyanide

Cited by 27 publications

References 27 publications

Renieramycin T Induces Lung Cancer Cell Apoptosis by Targeting Mcl-1 Degradation: A New Insight in the Mechanism of Action

Renieramycin T Induces Lung Cancer Cell Apoptosis by Targeting Mcl-1 Degradation: A New Insight in the Mechanism of Action

Asymmetric Synthesis and Cytotoxicity Evaluation of Right-Half Models of Antitumor Renieramycin Marine Natural Products

Construction of the Pentacyclic Core and Formal Total Synthesis of (rac)‐Renieramycin T

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