Semisynthesis of 5-O-ester derivatives of renieramycin T and their cytotoxicity against non-small-cell lung cancer cell lines.

The semisynthesis of 5-O-ester derivatives of renieramycin T was accomplished through the photoredox reaction of renieramycin M (1), a bistetrahydroisoquinolinequinone alkaloid isolated from the Thai blue sponge Xestospongia sp. This process led to the conversion of compound 1 to renieramycin T (2), which was subsequently subjected to Steglich esterification with appropriate acylating agents containing linear alkyl, N-tert-butoxycarbonyl-L-amino, and heterocyclic aromatic substituent. Notably, the one-pot transformation, combining the photoredox reaction and esterification led to the formation of 7-O-ester derivatives of renieramycin S due to hydrolysis.

Light-Mediated Transformation of Renieramycins and Semisynthesis of 4'-Pyridinecarbonyl-Substituted Renieramycin-Type Derivatives as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells.

The semisynthesis of renieramycin-type derivatives was achieved under mild and facile conditions by attaching a 1,3-dioxole-bridged phenolic moiety onto ring A of the renieramycin structure and adding a 4'-pyridinecarbonyl ester substituent at its C-5 or C-22 position. These were accomplished through a light-induced intramolecular photoredox reaction using blue light (4 W) and Steglich esterification, respectively. Renieramycin M (), a bis-tetrahydroisoquinolinequinone compound isolated from the Thai blue sponge ( sp.

Transformation of Renieramycin M into Renieramycins T and S by Intramolecular Photoredox Reaction of 7-Methoxy-6-methyl-1,2,3,4-tetrahydroisoquinoline-5,8-dione Derivatives.

In connection with our studies of biologically active 1,2,3,4-tetrahydroisoquinoline marine natural products, we describe herein a useful intramolecular photoredox transformation of 7-methoxy-6-methyl-1,2,3,4-tetrahydroisoquinoline-5,8-dione tricyclic models into 5-hydroxy-tetrahydroisoquinol[1,3]dioxoles in excellent yields. We applied this methodology to the transformation of renieramycin M into renieramycins T and S and the transformation of saframycin A. The results of cytotoxicity studies are also presented.

5--(-Boc-l-Alanine)-Renieramycin T Induces Cancer Stem Cell Apoptosis via Targeting Akt Signaling.

Cancer stem cells (CSCs) drive aggressiveness and metastasis by utilizing stem cell-related signals. In this study, 5--(-Boc-l-alanine)-renieramycin T (OBA-RT) was demonstrated to suppress CSC signals and induce apoptosis. OBA-RT exerted cytotoxic effects with a half-maximal inhibitory concentration of approximately 7 µM and mediated apoptosis as detected by annexin V/propidium iodide using flow cytometry and nuclear staining assays.

22-O-(N-Boc-L-glycine) ester of renieramycin M inhibits migratory activity and suppresses epithelial-mesenchymal transition in human lung cancer cells.

The incidence of metastasis stage crucially contributes to high recurrence and mortality rate in lung cancer patients. Unfortunately, no available treatment inhibits migration, a key metastasis process in lung cancer. In this study, the effect of 22-O-(N-Boc-L-glycine) ester of renieramycin M (22-Boc-Gly-RM), a semi-synthetic amino ester derivative of bistetrahydroisoquinolinequinone alkaloid isolated from Xestospongia sp.

Jorunnamycin A Suppresses Stem-Like Phenotypes and Sensitizes Cisplatin-Induced Apoptosis in Cancer Stem-Like Cell-Enriched Spheroids of Human Lung Cancer Cells.

It has been recognized that cancer stem-like cells (CSCs) in tumor tissue crucially contribute to therapeutic failure, resulting in a high mortality rate in lung cancer patients. Due to their stem-like features of self-renewal and tumor formation, CSCs can lead to drug resistance and tumor recurrence. Herein, the suppressive effect of jorunnamycin A, a bistetrahydroisoquinolinequinone isolated from Thai blue sponge sp.

Chemistry of Renieramycins. Part 19: Semi-Syntheses of 22--Amino Ester and Hydroquinone 5--Amino Ester Derivatives of Renieramycin M and Their Cytotoxicity against Non-Small-Cell Lung Cancer Cell Lines.

Two new series of synthetic renieramycins including 22--amino ester and hydroquinone 5--amino ester derivatives of renieramycin M were semi-synthesized and evaluated for their cytotoxicity against the metastatic non-small-cell lung cancer H292 and H460 cell lines. Interestingly, the series of 22--amino ester derivatives displayed a potent cytotoxic activity greater than the hydroquinone derivatives. The most cytotoxic derivative of the series was the 22--(-Boc-l-glycine) ester of renieramycin M (: IC 3.

Synergistic Cytotoxicity of Renieramycin M and Doxorubicin in MCF-7 Breast Cancer Cells.

Renieramycin M (RM) is a KCN-stabilized tetrahydroisoquinoline purified from the blue sponge sp., with nanomolar ICs against several cancer cell lines. Our goal is to evaluate its combination effects with doxorubicin (DOX) in estrogen receptor positive MCF-7 breast cancer cells.

Jorunnamycin A from sp. Suppresses Epithelial to Mesenchymal Transition and Sensitizes Anoikis in Human Lung Cancer Cells.

Metastasis is a key driving force behind the high mortality rate associated with lung cancer. Herein, we report the first study revealing the antimetastasis activity of jorunnamycin A, a bistetrahydroisoquinolinequinone isolated from a Thai blue sponge sp. evidenced by its inhibition of epithelial to mesenchymal transition (EMT), sensitization of anoikis, and suppression of anchorage-independent survival in human lung cancer cells.

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

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.

5-O-Acetyl-Renieramycin T from Blue Sponge Xestospongia sp. Induces Lung Cancer Stem Cell Apoptosis.

Lung cancer is one of the most significant cancers as it accounts for almost 1 in 5 cancer deaths worldwide, with an increasing incident rate. Management of the cancer has been shown to frequently fail due to the ability of the cancer cells to resist therapy as well as metastasis. Recent evidence has suggested that the poor response to the current treatment drugs and the ability to undergo metastasis are driven by cancer stem cells (CSCs) within the tumor.

Apoptosis-inducing Effect of Hydroquinone 5--Cinnamoyl Ester Analog of Renieramycin M on Non-small Cell Lung Cancer Cells.

Background: A newly-synthesized derivative of renieramycin M (RM), an anticancer lead compound isolated from the blue sponge Xestospongia sp., hydroquinone 5-O-cinnamoyl ester (CIN-RM), was investigated here for its activity against non-small cell lung cancer cells.

Materials And Methods: Cytotoxicity effects of CIN-RM and RM on H292 lung cancer cells were determined by the MTT assay.

Semisynthesis and biological evaluation of prenylated resveratrol derivatives as multi-targeted agents for Alzheimer's disease.

A series of prenylated resveratrol derivatives were designed, semisynthesized and biologically evaluated for inhibition of β-secretase (BACE1) and amyloid-β (Aβ) aggregation as well as free radical scavenging and neuroprotective and neuritogenic activities, as potential novel multifunctional agents against Alzheimer's disease (AD). The results showed that compound 4b exhibited good anti-Aβ aggregation (IC = 4.78 µM) and antioxidant activity (IC = 41.

Chemistry of Renieramycins. 17. A New Generation of Renieramycins: Hydroquinone 5-O-Monoester Analogues of Renieramycin M as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells.

A series of hydroquinone 5-O-monoester analogues of renieramycin M were semisynthesized via bishydroquinonerenieramycin M (5) prepared from renieramycin M (1), a major cytotoxic bistetrahydroisoquinolinequinone alkaloid isolated from the Thai blue sponge Xestospongia sp. All 20 hydroquinone 5-O-monoester analogues possessed cytotoxicity with IC values in nanomolar concentrations against the H292 and H460 human non-small-cell lung cancer (NSCLC) cell lines. The improved cytotoxicity toward the NSCLC cell lines was observed from the 5-O-monoester analogues such as 5-O-acetyl ester 6a and 5-O-propanoyl ester 7e, which exhibited 8- and 10-fold increased cytotoxicity toward the H292 NSCLC cell line (IC 3.

Renieramycin M Attenuates Cancer Stem Cell-like Phenotypes in H460 Lung Cancer Cells.

Background/aim: Cancer stem cells (CSCs) are a subpopulation of cancer cells that possess self-renewal and differentiation capacities. CSCs contribute to drug-resistance, cancer recurrence and metastasis, thus development of CSC-targeted therapeutic strategies has recently received significant attention in cancer research. In this study, the potential efficacy of renieramycin M (RM) isolated from the sponge Xestospongia species, was examined against lung CSCs.

Phenanthrenes from Eulophia macrobulbon as Novel Phosphodiesterase-5 Inhibitors.

Phosphodiesterase 5 (PDE5) inhibitors can be used for the treatment of erectile dysfunction and pulmonary hypertension. In order to search for new leads of PDE5 inhibitors, we investigated the chemical constituents of the tubers of Eulophia macrobulbon (E.C.

Bishydroquinone Renieramycin M Induces Apoptosis of Human Lung Cancer Cells Through a Mitochondria-dependent Pathway.

Background: Renieranycin M (RM), a bistetrahydro-isoquinolinequinone isolated from the Thai blue sponge, Xestospongia sp. was reported to be a potent anti-lung cancer agent. Modification at quinone ring enhanced apoptosis over necrosis.

Chemistry of Renieramycins. 15. Synthesis of 22-O-Ester Derivatives of Jorunnamycin A and Their Cytotoxicity against Non-Small-Cell Lung Cancer Cells.

Eighteen 22-O-ester derivatives of jorunnamycin A (2) were prepared via 2, and their cytotoxicity against human non-small-cell lung cancer (NSCLC) cells was evaluated. Preliminary study of the structure-cytotoxicity relationship revealed that the ester part containing a nitrogen-heterocyclic ring elevated the cytotoxicity of the 22-O-ester derivatives. Among them, 22-O-(4-pyridinecarbonyl) ester 6a is the most potent compound (IC50 1.

Chemistry of Ecteinascidins. Part 5: An Additional Proof of Cytotoxicity Evaluation of Ecteinascidin 770 Derivatives.

Eleven 2'-N-acyl derivatives (5a-k) were prepared from ecteinascidin 770 (Et 770: 1b) via known 18,6'-O-bisallyl-protected compound (3) in three steps. Their in vitro cytotoxicities were determined by measuring IC50 values against human cell lines HCT116 and DU145. 5-Isoxazolecarboylamide derivative (5i) and 4-methoxybenzoylamide derivative (5k) were found to be promising leads for further optimization.

Streptomyces verrucosisporus sp. nov., isolated from marine sediments.

Five actinomycete isolates, CPB1-1T, CPB2-10, BM1-4, CPB3-1 and CPB1-18, belonging to the genus Streptomyces were isolated from marine sediments collected from Chumphon Province, Thailand. They produced open loops of warty spore chains on aerial mycelia. ll-Diaminopimelic acid, glucose and ribose were found in their whole-cell hydrolysates.

Micromonospora sediminis sp. nov., isolated from mangrove sediment.

The novel actinomycete, strain CH3-3T, was isolated from mangrove sediment collected from Chonburi Province, Thailand. On the basis of its spore morphology and chemotaxonomic characteristics, the strain belonged to the genus Micromonospora. It contained meso-diaminopimelic acid, glucose, mannose, xylose, ribose and rhamnose in the whole-cell hydrolysate, MK-10(H4), MK-10(H6) and MK-10(H8) as major menaquinones, and iso-C15 : 0, iso-C16 : 0 and iso-C17 : 0 as major cellular fatty acids.

Renieramycin M Sensitizes Anoikis-resistant H460 Lung Cancer Cells to Anoikis.

Background/aim: Anoikis resistance plays a crucial role in the promotion of survival of circulating tumor cells. This study aimed to evaluate the mechanistic pathways of anoikis resistance in human lung cancer cells and test the possible therapeutic effect of renieramycin M (RM) from the sponge Xestospongia sp. in conversion of anoikis resistance.

Synthesis and Absolute Configuration of Acanthodendrilline, a New Cytotoxic Bromotyrosine Alkaloid from the Thai Marine Sponge Acanthodendrilla sp.

Acanthodendrilline (1), a new bromotyrosine alkaloid, was isolated from the Thai marine sponge Acanthodendrilla sp. The structure of 1 was fully characterized by spectroscopic analysis, in agreement with the synthesized compound used to resolve the single chiral center at C-11. Total synthesis of the enantiomers of 1 allowed for the comparison of specific rotation values and hence the determination of the absolute configuration as 11-S.

Streptomyces andamanensis sp. nov., isolated from soil.

A novel actinomycete, strain KC-112T, was isolated from soil collected from Similan Islands, Phang-Nga Province, Thailand. The strain exhibited morphological and chemotaxonomic characteristics consistent with those of members of the genus Streptomyces. The formation of smooth spiral spore chains was observed on aerial mycelia.