Synthesis and antitumor activity of ATB-429 derivatives containing a nitric oxide-releasing moiety

Wang, Chunlan; Xia, Guimin; Liu, Xiujun; Zhang, Rui; Chai, Yun; Zhang, Jun; Li, Xiaoning; Yang, Yang; Wang, Juxian; Liu, Mingliang

doi:10.1016/j.bmcl.2016.03.012

Cited by 11 publications

(4 citation statements)

References 22 publications

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“…The first report on this compound demonstrated superior anti-inflammatory and antinociceptive efficacy compared with the base mesalamine molecule in a rodent experimental model of colitis-associated colorectal distension (Distrutti et al, 2006), and additional studies demonstrated its efficacy and safety in animal models of colitis (Fiorucci et al, 2007). Most recently, a series of combined NO/H 2 Sreleasing ATB-429 derivatives have been synthesized, with antitumor effects in vitro (Wang et al, 2016a). Li et al (2007) reported on the biologic effects of a H 2 S-releasing diclofenac derivative (ACS15, or S-diclofenac (2-[(2,6-dichlorophenyl)amino]benzene acetic acid 4-(3H-1,2,dithiol-3-thione-5-yl)phenyl ester) (Fig.…”

Section: Combined (Or Hybrid) Molecules: H 2 S-donating Derivamentioning

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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Section: Combined (Or Hybrid) Molecules: H 2 S-donating Derivamentioning

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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“…In vivo investigation revealed that NOSH-aspirin caused an 85% reduction in the volume of human colon cancer xenografts in mice. Currently, studies aiming to develop NOSH-aspirin analogues and to clarify the structure–activity relationship of these compounds are in progress. , Meanwhile, the “dual donor” strategy has been applied to produce NOSH-sulindac ( 55 ) (Figure ), which inhibited the growth of several human cancer cells at rates 1000–9000 times more potent than sulindac …”

Section: Therapeutic Applications Of No Donor-based Therapymentioning

confidence: 99%

Nitric Oxide Donor-Based Cancer Therapy: Advances and Prospects

2017

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The increasing understanding of the role of nitric oxide (NO) in cancer biology has generated significant progress in the use of NO donor-based therapy to fight cancer. These advances strongly suggest the potential adoption of NO donor-based therapy in clinical practice, and this has been supported by several clinical studies in the past decade. In this review, we first highlight several types of important NO donors, including recently developed NO donors bearing a dinitroazetidine skeleton, represented by RRx-001, with potential utility in cancer therapy. Special emphasis is then given to the combination of NO donor(s) with other therapies to achieve synergy and to the hybridization of NO donor(s) with an anticancer drug/agent/fragment to enhance the activity or specificity or to reduce toxicity. In addition, we briefly describe inducible NO synthase gene therapy and nanotechnology, which have recently entered the field of NO donor therapy.

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“…1,2-Dithioles have been an important class of sulfur heterocycles since 1884, when the first representative of this class, 4,5-dimethyl-1,2-dithiole-3-thione (1) was synthesized [1]. 1,2-Dithiole derivatives show many types of significant pharmacological activity, including antitumor, antioxidant, chemotherapeutic, antithrombotic and radioprotective properties [2][3][4][5][6][7][8][9]. In addition to the above applications, 1,2-dithioles show anti-HIV activity [10,11].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Reactivity of 3H-1,2-dithiole-3-thiones

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2021

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3H-1,2-Dithiole-3-thiones are among the best studied classes of polysulfur-containing heterocycles due to the almost explosive recent interest in these compounds as sources of hydrogen sulfide as an endogenously produced gaseous signaling molecule. This review covers the recent developments in the synthesis of these heterocycles, including both well-known procedures and important novel transformations for building the 1,2-dithiole-3-thione ring. Diverse ring transformations of 3H-1,2-dithiole-3-thiones into various heterocyclic systems through 1,3-dipolar cycloaddition, replacement of one or two sulfur atoms to form carbon- and carbon-nitrogen containing moieties, and other unexpected reactions are considered.

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Synthesis and antitumor activity of ATB-429 derivatives containing a nitric oxide-releasing moiety

Cited by 11 publications

References 22 publications

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

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

Nitric Oxide Donor-Based Cancer Therapy: Advances and Prospects

Synthesis and Reactivity of 3H-1,2-dithiole-3-thiones

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Synthesis and antitumor activity of ATB-429 derivatives containing a nitric oxide-releasing moiety

Cited by 11 publications

References 22 publications

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

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

Nitric Oxide Donor-Based Cancer Therapy: Advances and Prospects

Synthesis and Reactivity of 3H-1,2-dithiole-3-thiones

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

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