4-Aminoquinoline-hybridization en route towards the development of rationally designed antimalarial agents

Raj, Raghu; Land, Kirkwood M.; Kumar, Vipan

doi:10.1039/c5ra16361g

Cited by 28 publications

(10 citation statements)

References 123 publications

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“…MH is performed to achieve one of the following objectives: (i) synergism of pharmacological action, (ii) dual action therapy pharmacological or (iii) modulation of undesirable side effects. 3 The synergistic action hybrid is obtained when pharmacophoric groups or whole drugs are covalently linked. Both should have the same pharmacological action, but should act on different biochemical targets.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Molecular Modelling and Anticancer Activities of New Molecular Hybrids Containing 1,4-Naphthoquinone, 7-Chloroquinoline, 1,3,5-Triazine and Morpholine Cores as PI3K and AMPK Inhibitors in the Metastatic Melanoma Cells

Fiorot

Westphal

Lemos

et al. 2019

J. Braz. Chem. Soc.

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Three molecular hybrids containing 1,4-naphthoquinones, 1,3,5-triazines, morpholine and 7-chloroquinoline, which have recognized contributions to the biological activity of many drugs, were synthesized in yields ranging from 43-84%. All hybrids were obtained in three steps starting from readily available reactants: lawsone, cyanuric chloride, morpholine and 4,7-dichloroquinoline. A previous docking study was carried out to identify the binding energy and pharmacophore conformation of the promising anticancer compounds with PI3Kγ (phosphoinositide 3-kinase) and AMPK (5' AMP-activated protein kinase). The cancer activity in human metastatic melanoma cells (SKMEL-103) were performed, and the synthetized compounds presented half maximal inhibitory concentration (IC 50) values around 25 μM. The expressions of PI3K and AMPK were also determined using western blotting technique, and all molecular hybrids negatively modulated both targets.

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Section: Introductionmentioning

confidence: 99%

Synthesis, Molecular Modelling and Anticancer Activities of New Molecular Hybrids Containing 1,4-Naphthoquinone, 7-Chloroquinoline, 1,3,5-Triazine and Morpholine Cores as PI3K and AMPK Inhibitors in the Metastatic Melanoma Cells

Fiorot

Westphal

Lemos

et al. 2019

J. Braz. Chem. Soc.

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“…Hybridization of molecules is a new idea in drug design and development that is based on the combination of different bioactive moieties to produce new hybrid compounds with better effectiveness than the parent drugs . The 1,3‐dipolar cycloaddition reaction is an expedient tool for molecular hybridization because it can afford two (or more) bioactive scaffolds in one molecule in a one‐step reaction: one is a pyrrolidine and the other is from the bioactive moiety in a counterpart alkene .…”

Section: Introductionmentioning

confidence: 99%

Copper‐Catalyzed Regio‐ and Diastereoselective 1,3‐Dipolar Cycloaddition Reactions of Glycine Imino Esters with 1‐Propene‐1,3‐sultone

et al. 2019

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The 1,3‐dipolar cycloaddition of glycine imino esters (azomethine ylide precursors) with 1‐propene‐1,3‐sultone proceeded smoothly by using copper phosphine complexes at room temperature to give the bicyclic sultone‐fused pyrrolidines as single regio‐ and stereoisomers in good yields. A preliminary asymmetric reaction with a chiral copper complex gave the fused sultone‐pyrrolidine with excellent enantioselectivity.

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“…More than a decade ago, the combination therapy which involves the combination of two or more antimalarials has been reported to be the future approach to overcome drug resistance of antimalarials. Hybridization approach has also been utilized, it involves the combination of two distinctive pharmacophoric features from new and known drugs to form a molecule with enhanced efficacy against most of the malaria stages [ 5 , 7 ]. Antimalarial drugs containing 4-aminoquinoline scaffolds are good precursors for hybridization with other antimalarials and metal-based compounds via selected functionalities [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Quinoline-Based Hybrid Compounds with Antimalarial Activity

2017

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The application of quinoline-based compounds for the treatment of malaria infections is hampered by drug resistance. Drug resistance has led to the combination of quinolines with other classes of antimalarials resulting in enhanced therapeutic outcomes. However, the combination of antimalarials is limited by drug-drug interactions. In order to overcome the aforementioned factors, several researchers have reported hybrid compounds prepared by reacting quinoline-based compounds with other compounds via selected functionalities. This review will focus on the currently reported quinoline-based hybrid compounds and their preclinical studies.

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4-Aminoquinoline-hybridization en route towards the development of rationally designed antimalarial agents

Abstract: Recent developments in 4-aminoquinoline-hybridization, as an attractive strategy for averting and delaying the drug resistance along with improvement in efficacy of new antimalarials, are described.

Cited by 28 publications

References 123 publications

Synthesis, Molecular Modelling and Anticancer Activities of New Molecular Hybrids Containing 1,4-Naphthoquinone, 7-Chloroquinoline, 1,3,5-Triazine and Morpholine Cores as PI3K and AMPK Inhibitors in the Metastatic Melanoma Cells

Synthesis, Molecular Modelling and Anticancer Activities of New Molecular Hybrids Containing 1,4-Naphthoquinone, 7-Chloroquinoline, 1,3,5-Triazine and Morpholine Cores as PI3K and AMPK Inhibitors in the Metastatic Melanoma Cells

Copper‐Catalyzed Regio‐ and Diastereoselective 1,3‐Dipolar Cycloaddition Reactions of Glycine Imino Esters with 1‐Propene‐1,3‐sultone

Quinoline-Based Hybrid Compounds with Antimalarial Activity

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