Synthesis and evaluation of furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline as anticancer and multidrug resistance reversal agents

Zou, Zhi-Hong; Lan, Xiaobu; Qian, Hai; Huang, Wenlong; Li, Yunman

doi:10.1016/j.bmcl.2011.07.077

Cited by 19 publications

(14 citation statements)

References 17 publications

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“…), which possess cytotoxic activity against varioush uman cancer cell lines superior to parent drugs and that are less toxic toward normal cells. [60][61][62][63][64][65][66][67] Cytotoxic activity of furoxan-derived hybridsc an also be achieved through the design of novel histone deacetylase (HDAC) inhibitors, as abnormal HDAC activity was found to stimulate aberrant gene expression andt hus the distribution of several types of cancer.R ecently,t his approach wasr ealized throught he synthesis of furoxan-hydroxamic acid hybrid 108 (Scheme 34), which was shown to be capable of simultaneous NO release and selectiveH DAC6 inhibition, resulting in as ignificant antiproliferative effect. [68] Another type of multitarget drug, NO-MS275, based on the molecular hybridization of af uroxans caffoldw ith entinostat, Scheme31.…”

Section: Introductionmentioning

confidence: 99%

Molecular Hybridization Tools in the Development of Furoxan‐Based NO‐Donor Prodrugs

Ферштат

Махова

2017

ChemMedChem

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The molecular hybridization of different compounds with known pharmacological activity is a particularly prominent approach for the design of potential drugs with improved pharmacokinetic profiles. Much attention over the last decade has been focused on the synthesis of hybrid structures with a nitric oxide (NO)-donor framework, as NO is a ubiquitous and crucial regulator of cellular metabolism, affecting various physiological and pathophysiological processes. 1,2,5-Oxadiazole 2-oxides (furoxans), which are capable of exogenous NO release in the presence of thiol cofactors, are an important class of prospective NO donors. As such, a wide range of hybrid compounds that combine a furoxan ring with various pharmacologically active structures have been created. This review focuses on recent results in the synthesis and pharmacological activity of furoxan-based hybrids. Special attention is given to chemo- and regioselective methods used in the preparation of these hybrid structures, and the role of synergistic effects on their pharmacological activity, associated with the furoxan fragment.

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Section: Introductionmentioning

confidence: 99%

Molecular Hybridization Tools in the Development of Furoxan‐Based NO‐Donor Prodrugs

Ферштат

Махова

2017

ChemMedChem

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“…Interestingly, Zou et al . reported that some furoxan‐based nitric oxide‐releasing derivatives of tetrahydroisoquinoline exhibited potent MDR reversal activities on K562/A02 cell line, suggesting that cytotoxic activities increased as the increasing concentration of nitric oxide production . In our study, DDB‐nitric oxide has the same nitric oxide‐releasing moiety (furoxan) but different scaffold (DDB) and spacer.…”

Section: Discussionmentioning

confidence: 64%

“…Various types of nitric oxide donor or mimetics, such as s-nitrosopenicillamin and nitroglycerine, have been reported to reverse the resistance by inhibiting drug efflux mediated by MDR-ABC transporters in vitro and in vivo [23,24]. Interestingly, Zou et al reported that some furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline exhibited potent MDR reversal activities on K562/A02 cell line, suggesting that cytotoxic activities increased as the increasing concentration of nitric oxide production [25]. In our study, DDBnitric oxide has the same nitric oxide-releasing moiety (furoxan) but different scaffold (DDB) and spacer.…”

Section: Discussionmentioning

confidence: 99%

Anticancer efficacy of a nitric oxide‐modified derivative of bifendate against multidrug‐resistant cancer cells

Ren

Lü

et al. 2016

J Cellular Molecular Medi

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The development of multidrug resistance (MDR) not only actively transports a wide range of cytotoxic drugs across drug transporters but is also a complex interaction between a number of important cellular signalling pathways. Nitric oxide donors appear to be a new class of anticancer therapeutics for satisfying all the above conditions. Previously, we reported furoxan‐based nitric oxide‐releasing compounds that exhibited selective antitumour activity in vitro and in vivo. Herein, we demonstrate that bifendate (DDB)‐nitric oxide, a synthetic furoxan‐based nitric oxide‐releasing derivative of bifendate, effectively inhibits the both sensitive and MDR tumour cell viability at a comparatively low concentration. Interestingly, the potency of DDB‐nitric oxide is the independent of inhibition of the functions and expressions of three major ABC transporters. The mechanism of DDB‐nitric oxide appears to be in two modes of actions by inducing mitochondrial tyrosine nitration and apoptosis, as well as by down‐regulating HIF‐1α expression and protein kinase B (AKT), extracellular signal‐regulated kinases (ERK), nuclear factor κB (NF‐κB) activation in MDR cells. Moreover, the addition of a typical nitric oxide scavenger significantly attenuated all the effects of DDB‐nitric oxide, indicating that the cytotoxicity of DDB‐nitric oxide is as a result of higher levels of nitric oxide release in MDR cancer cells. Given that acquired MDR to nitric oxide donors is reportedly difficult to achieve and genetically unstable, compound like DDB‐nitric oxide may be a new type of therapeutic agent for the treatment of MDR tumours.

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“…Konstantin et al reported that conjugation of doxorubicin with NO donor inducd high cytotoxicity in doxorubicinresistant human colon cancer cells (Konstantin et al, 2011). NO-releasing derivatives of tetrahydroisoquinoline had anticancer effects, as well as multidrug resistance reversal effects (Zou et al, 2011). As an important class of NO donor, furoxans have been found to possess a NOrelated biological activity, antileukemic activity, and have been expected as promising lead compounds to develop novel antileukemic agents (Bian et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Preparation and Antitumor Activity of a Tamibarotene-Furoxan Derivative

Wang¹,

Duan²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Multi-target drug design, in which drugs are designed as single molecules to simultaneously modulate multiple physiological targets, is an important strategy in the field of drug discovery. QT-011, a tamibarotene-furoxan derivative, was here prepared and proposed to exert synergistic effects on antileukemia by releasing nitric oxide and tamibarotene. Compared with tamibarotene itself, QT-011 displayed stronger antiproliferative effects on U937 and HL-60 cells and was more effective evaluated in a nude mice U937 xenograft model in vivo. In addition, QT-011 could release nitric oxide which might contribute to the antiproliferative activity. Autodocking assays showed that QT-011 fits well with the hydrophobic pocket of retinoic acid receptors. Taken together, these results suggest that QT-011 might be a highly effective derivative of tamibarotene and a potential candidate compound as antileukemia agent.

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Synthesis and evaluation of furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline as anticancer and multidrug resistance reversal agents

Cited by 19 publications

References 17 publications

Molecular Hybridization Tools in the Development of Furoxan‐Based NO‐Donor Prodrugs

Molecular Hybridization Tools in the Development of Furoxan‐Based NO‐Donor Prodrugs

Anticancer efficacy of a nitric oxide‐modified derivative of bifendate against multidrug‐resistant cancer cells

Preparation and Antitumor Activity of a Tamibarotene-Furoxan Derivative

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