Synthesis and evaluation of 7-chloro-4-(piperazin-1-yl)quinoline-sulfonamide as hybrid antiprotozoal agents

Salahuddin, Attar; Inam, Afreen; Zyl, Robyn L. van; Heslop, Donovan C; Chen, Chien-Teng; Avecilla, Fernando; Agarwal, Subhash Mohan; Azam, Amir

doi:10.1016/j.bmc.2013.03.052

Cited by 55 publications

(30 citation statements)

References 44 publications

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“…Flash chromatography was performed on silica gel 60 (0.040 to 0.063 mm) purchased from SiliCycle or Merck. The structures of synthesized compounds were verified by 1 H nuclear magnetic resonance (NMR), 13 C NMR, and mass spectrometry (MS).…”

Section: Methodsmentioning

confidence: 99%

“…1 H (400 MHz) and 13 C (101 MHz) NMR spectra were measured in CDCl 3 on a Bruker Avance III 400 (Ultrashield Plus) spectrometer. Chemical shifts are reported in parts per million (ppm) using the residual CDCl 3 peak at 7.26 ( 1 H) or 77.16 ( 13 C) as the internal standard.…”

Section: Methodsmentioning

confidence: 99%

“…One example of a combination strategy to create single-molecule drugs is to combine artemisinin and quinine (compound 2) (10-12); another strategy is to combine antimalarial agents with other scaffolds such as compound 3 ( Fig. 2) (13,14). There are also a few reported examples of CRAs combined to compound 1, aiming to have antimalarial activity of CQ and at the same time blocking the P. falciparum chloroquine resistance transporter (PfCRT) with the CRA (15)(16)(17).…”

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confidence: 99%

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Overcoming Chloroquine Resistance in Malaria: Design, Synthesis, and Structure-Activity Relationships of Novel Hybrid Compounds

Boudhar

Loh

et al. 2016

Antimicrob Agents Chemother

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dResistance to antimalarial therapies, including artemisinin, has emerged as a significant challenge. Reversal of acquired resistance can be achieved using agents that resensitize resistant parasites to a previously efficacious therapy. Building on our initial work describing novel chemoreversal agents (CRAs) that resensitize resistant parasites to chloroquine (CQ), we herein report new hybrid single agents as an innovative strategy in the battle against resistant malaria. Synthetically linking a CRA scaffold to chloroquine produces hybrid compounds with restored potency toward a range of resistant malaria parasites. A preferred compound, compound 35, showed broad activity and good potency against seven strains resistant to chloroquine and artemisinin. Assessment of aqueous solubility, membrane permeability, and in vitro toxicity in a hepatocyte line and a cardiomyocyte line indicates that compound 35 has a good therapeutic window and favorable drug-like properties. This study provides initial support for CQ-CRA hybrid compounds as a potential treatment for resistant malaria.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Overcoming Chloroquine Resistance in Malaria: Design, Synthesis, and Structure-Activity Relationships of Novel Hybrid Compounds

Boudhar

Loh

et al. 2016

Antimicrob Agents Chemother

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“…10 Therefore, we planned to construct derivatives of (14) by simple substitution of the bromine with hetrocyclic rings. This substitution procedure would enable the introduction of heteroatoms via an SNAr method due to the activation of bromine group on the quinoline core by the nitro group, due to its strong electon-withdrawing effect, which could lead to other potentially bioactive molecules.…”

Section: Introductionmentioning

confidence: 99%

“…Although the piperazine-and morpholine-substituted quinolines have a wide range of biological importance, [13][14] the available literature lacks syntheses of these piperazine-and morpholine-based derivatives on the benzene ring of quinolines by substitution methods.…”

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confidence: 99%

Activation of 6-bromoquinoline by nitration: synthesis of morpholinyl and piperazinyl quinolines

Çakmak¹,

Ökten²,

Alimli³

et al. 2018

Arkivoc

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Quinoline forms the key skeletal component of a number of important natural products and pharmacologicallyactive compounds. Despite a tremendous amount of research pertaining to the derivatization of quinoline, very few general synthetic routes are described in the literature starting from quinoline or tetrahydroquinoline. A simple and convenient method for the polyfunctionalization of quinolines via nitration of bromoquinolines has been developed. This method represents a new synthetic approach to convert brominated nitroquinoline derivatives into useful cyclic amines via nucleophilic-substitution (SNAr) reaction.

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Direct Carbamoylation of Quinoline N‐oxides with Hydrazinecarboxamides via C−H Bond Activation Catalyzed by Copper Catalyst

Dong

Yang

et al. 2019

Adv Synth Catal

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Synthesis and evaluation of 7-chloro-4-(piperazin-1-yl)quinoline-sulfonamide as hybrid antiprotozoal agents

Cited by 55 publications

References 44 publications

Overcoming Chloroquine Resistance in Malaria: Design, Synthesis, and Structure-Activity Relationships of Novel Hybrid Compounds

Overcoming Chloroquine Resistance in Malaria: Design, Synthesis, and Structure-Activity Relationships of Novel Hybrid Compounds

Activation of 6-bromoquinoline by nitration: synthesis of morpholinyl and piperazinyl quinolines

Direct Carbamoylation of Quinoline N‐oxides with Hydrazinecarboxamides via C−H Bond Activation Catalyzed by Copper Catalyst

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