Marine natural products as inhibitors of cystathionine beta-synthase activity

Thorson, Megan K.; Wagoner, Ryan M. Van; Harper, Mary Kay; Ireland, Chris M.; Majtán, Tomáš; Kraus, Jan P.; Barrios, Amy

doi:10.1016/j.bmcl.2015.01.013

Cited by 20 publications

(12 citation statements)

References 20 publications

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“…Intriguingly, both the compounds have been suggested as potential anti-cancer molecules, especially for colon cancer in other studies (129,191). Using a library of marine natural products (MICL-240 library), Barrios and colleagues (280) have recently performed another screen to identify novel CBS inhibitors. They (177).…”

Section: A Treatment Of Cancer With H 2 S Biosynthesis Inhibitorsmentioning

confidence: 99%

A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?

Cao

Ding

Xie

et al. 2019

Antioxidants & Redox Signaling

353

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Section: A Treatment Of Cancer With H 2 S Biosynthesis Inhibitorsmentioning

confidence: 99%

A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?

Cao

Ding

Xie

et al. 2019

Antioxidants & Redox Signaling

353

283

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“…After excluding those compounds that scavenged H 2 S or quenched the azidocoumarin fluorescence that was used to detect H 2 S, the authors proposed the diuretic amiloride and the DOPAdexarboxylase inhibitor benserazide as CBS inhibitors, with an IC 50 of 89 mM and an IC 25 125 mM, respectively. Τhe same group, after screening a library consisting of marine natural products and synthetic derivatives reported that their best hits were synthetic compounds derived from the polyandrocarpamines A and B; the potency of these derivatives was in the 100 mΜ range (Thorson et al, 2015). In another high-throughput assay, Zhou et al (2013) identified 1,6-dimethyl-pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-dione (NSC67078) as a CBS inhibitor with a modest (threefold) selectivity over CSE.…”

Section: Pharmacological Inhibitors Of Cystathionine-b-synthasementioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

2017

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Over the last decade, hydrogen sulfide (HS) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to the previously characterized gasotransmitters nitric oxide and carbon monoxide, HS is produced by various enzymatic reactions and regulates a host of physiologic and pathophysiological processes in various cells and tissues. HS levels are decreased in a number of conditions (e.g., diabetes mellitus, ischemia, and aging) and are increased in other states (e.g., inflammation, critical illness, and cancer). Over the last decades, multiple approaches have been identified for the therapeutic exploitation of HS, either based on HS donation or inhibition of HS biosynthesis. HS donation can be achieved through the inhalation of HS gas and/or the parenteral or enteral administration of so-called fast-releasing HS donors (salts of HS such as NaHS and NaS) or slow-releasing HS donors (GYY4137 being the prototypical compound used in hundreds of studies in vitro and in vivo). Recent work also identifies various donors with regulated HS release profiles, including oxidant-triggered donors, pH-dependent donors, esterase-activated donors, and organelle-targeted (e.g., mitochondrial) compounds. There are also approaches where existing, clinically approved drugs of various classes (e.g., nonsteroidal anti-inflammatories) are coupled with HS-donating groups (the most advanced compound in clinical trials is ATB-346, an HS-donating derivative of the non-steroidal anti-inflammatory compound naproxen). For pharmacological inhibition of HS synthesis, there are now several small molecule compounds targeting each of the three HS-producing enzymes cystathionine--synthase (CBS), cystathionine--lyase, and 3-mercaptopyruvate sulfurtransferase. Although many of these compounds have their limitations (potency, selectivity), these molecules, especially in combination with genetic approaches, can be instrumental for the delineation of the biologic processes involving endogenous HS production. Moreover, some of these compounds (e.g., cell-permeable prodrugs of the CBS inhibitor aminooxyacetate, or benserazide, a potentially repurposable CBS inhibitor) may serve as starting points for future clinical translation. The present article overviews the currently known HS donors and HS biosynthesis inhibitors, delineates their mode of action, and offers examples for their biologic effects and potential therapeutic utility.

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“…These biomarkers, associated with epithelial-derived cell lines and also some colorectal, breast and lung cell lines, could be of use in predicting the likelihood of patient response to didemnin B or analogues in a therapeutic setting. Synthetic analogues related to the polyandrocarpamines 955 were found to be inhibitors of H 2 S production by cystathionine beta-synthase, 956 and SAR studies have been reported for thiaplidiaquinones A and B 957 (various biological targets), 958 cadiolides A-C 959,960 (antibacterial), 961,962 rubrolides 963 (photosynthesis inhibitors), 964 meridianins 965 (antimalarial and antituberculosis), 966 isogranulatimide 967 (cytotoxicity), 968 and lamellarins 969 (cytotoxicity). 970…”

Section: Molluscsmentioning

confidence: 99%

Marine natural products

et al. 2017

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Covering: 2015. Previous review: Nat. Prod. Rep., 2016, 33, 382-431This review covers the literature published in 2015 for marine natural products (MNPs), with 1220 citations (792 for the period January to December 2015) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1340 in 429 papers for 2015), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.

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Marine natural products as inhibitors of cystathionine beta-synthase activity

Cited by 20 publications

References 20 publications

A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?

A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

Marine natural products

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Marine natural products as inhibitors of cystathionine beta-synthase activity

Cited by 20 publications

References 20 publications

A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?

A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

Marine natural products

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Product

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International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors