2-Aryl-3H-indol-3-ones: Synthesis, electrochemical behaviour and antiplasmodial activities

Najahi, Ennaji; Valentin, Alexis; Fabre, Paul-Louis; Reybier, Karine; Nepveu, Françoise

doi:10.1016/j.ejmech.2014.03.059

Cited by 22 publications

(15 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This return to the original form produced free radicals. The production of radicals is fatal to the stability of parasitized RBCs and hence to the parasites while it induces no hemolytic effect in the healthy RBCs [ 8 , 30 ]. This result is highly interesting, because, to date, it was assumed that the activity of antimalarial compounds arose from their inhibition of hQR2.…”

Section: Discussionmentioning

confidence: 99%

“…All the indole derivatives (structures shown in Figure 1 ) were prepared in our laboratory, as previously described: 2-aryl-3 H -indol-3-one- N- oxides (INODs) [ 4 ], 2-aryl-3H-indol-3-ones (INDs) [ 30 ], 2-aryl-3 H -indol-3-ol and N -hydroxyindoles and 1- H -indoles [ 7 ]. The N -[2-(2-methoxy-6 H -dipyrido[2,3-a:3,2-e]pyrrolizin-11-yl)ethyl]-2-furamide (S29434) was prepared as described by Mailliet et al [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Role of Quinone Reductase 2 in the Antimalarial Properties of Indolone-Type Derivatives

et al. 2017

Self Cite

View full text Add to dashboard Cite

Indolone-N-oxides have antiplasmodial properties against Plasmodium falciparum at the erythrocytic stage, with IC50 values in the nanomolar range. The mechanism of action of indolone derivatives involves the production of free radicals, which follows their bioreduction by an unknown mechanism. In this study, we hypothesized that human quinone reductase 2 (hQR2), known to act as a flavin redox switch upon binding to the broadly used antimalarial chloroquine, could be involved in the activity of the redox-active indolone derivatives. Therefore, we investigated the role of hQR2 in the reduction of indolone derivatives. We analyzed the interaction between hQR2 and several indolone-type derivatives by examining enzymatic kinetics, the substrate/protein complex structure with X-ray diffraction analysis, and the production of free radicals with electron paramagnetic resonance. The reduction of each compound in cells overexpressing hQR2 was compared to its reduction in naïve cells. This process could be inhibited by the specific hQR2 inhibitor, S29434. These results confirmed that the anti-malarial activity of indolone-type derivatives was linked to their ability to serve as hQR2 substrates and not as hQR2 inhibitors as reported for chloroquine, leading to the possibility that substrate of hQR2 could be considered as a new avenue for the design of new antimalarial compounds.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Role of Quinone Reductase 2 in the Antimalarial Properties of Indolone-Type Derivatives

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…This includes the screening of synthetic and natural products with potential antimalarial activity [ 13 , 14 ]. Among them, we can mention the encapsulated synthetic protoporphyrins [ 15 , 16 ], hydroxynaphthoquinones [ 17 ] and indole compounds [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Plasmodium falciparum Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development

et al. 2020

View full text Add to dashboard Cite

The search for new compounds with antimalarial activity is urgent, as resistance to ones in the classical drug, has already been described in more than one continent. Compounds derived from 1,2,3-triazoles are effective against parasites and bacteria. Here, we evaluated the potential antimalarial activity against the human malaria parasite Plasmodium falciparum in a culture of fifty-four triazole compounds derived from 1H-and 2H-1,2,3-triazole. We identified thirty-one compounds with potential antimalarial activity at concentrations in the micromolar order (µM) and IC50 values ranging from 2.80 µM (9) to 29.27 µM (21). Then, we selected some of these compounds to perform the same tests on the PfSR25- strain (knockout for P. falciparum G-protein coupled receptor-like, SR25). Our experiences with the PfSR25- strain showed that both compounds with higher antimalarial activity for the 3D7 strain and those with less activity resulted in lower IC50 values for the knockout strain. The cytotoxicity of the compounds was evaluated in human renal embryonic cells (HEK 293), using MTT assays. This demonstrated that the compounds with the highest activity (9, 13, 19, 22, 24, 29), showed no toxicity at the tested concentrations.

show abstract

“…As far as we know, there has been no previous report on this transformation of 2‐alkynyl arylazides to 2‐(1 H ‐indol‐3‐yl)‐2‐phenylindolin‐3‐ones via one‐pot process in organic synthesis. It was noted that the key intermediate 2‐aryl‐3 H ‐indol‐3‐ones generated in situ from simple starting materials were very active and not easily prepared . This one‐pot process would also have significant potential as a novel strategy for the total synthesis of Isatisine A. Herein, we disclose a novel palladium‐catalyzed one‐pot preparation of indolin‐3‐ones bearing indoxyl group via 1 H ‐indole‐3‐sulfonates generated in situ from 2‐alkynyl arylazides.…”

Section: Introductionmentioning

confidence: 99%

Pd‐Catalyzed One‐Pot Two‐Step Synthesis of 2‐(1H‐indol‐3‐yl)‐2‐phenylindolin‐3‐ones from 2‐Alkynyl Arylazides and Indoles

Yong

Sheng

et al. 2018

ChemistrySelect

View full text Add to dashboard Cite

An efficient palladium‐catalyzed one‐pot two‐step reaction of 2‐alkynyl arylazides and indoles has been developed. The reaction proceeded well under mild reaction conditions and provided the 2‐(1H‐indole‐3‐yl)‐2‐phenylindolin‐3‐ones in good to excellent yields.This transformation involves a rearrangement of 1H‐indole‐3‐sulfonates generated in situ and Mannich‐type addition of indoline‐3‐ones.

show abstract

2-Aryl-3H-indol-3-ones: Synthesis, electrochemical behaviour and antiplasmodial activities

Cited by 22 publications

References 22 publications

Role of Quinone Reductase 2 in the Antimalarial Properties of Indolone-Type Derivatives

Role of Quinone Reductase 2 in the Antimalarial Properties of Indolone-Type Derivatives

Plasmodium falciparum Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development

Pd‐Catalyzed One‐Pot Two‐Step Synthesis of 2‐(1H‐indol‐3‐yl)‐2‐phenylindolin‐3‐ones from 2‐Alkynyl Arylazides and Indoles

Contact Info

Product

Resources

About