Recent developments in the design and synthesis of hybrid molecules basedon aminoquinoline ring and their antiplasmodial evaluation

Kouznetsov, Vladímir V.; Gómez‐Barrio, Alicia

doi:10.1016/j.ejmech.2009.02.024

Cited by 146 publications

(69 citation statements)

References 185 publications

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“…The alkylamine sidechains allow for structural modification of the 4-aminoquinolines, resulting in compounds that have different lipophilicity and drug-resistance profiles (Kouznetsov & Gómez-Barrio 2009). Substitutions on the distal amino sidechain of CQ derivatives increase the activity and decrease the cross-resistance to CQ (Stocks et al 2002).…”

Section: Drug Combinations and Hybrids Used In Antimalarial Chemothermentioning

confidence: 99%

New approaches in antimalarial drug discovery and development: a review

Aguiar

Rocha

Souza

et al. 2012

Mem. Inst. Oswaldo Cruz

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Malaria remains a major world health problem following the emergence and spread of Plasmodium falciparum that is resistant to the majority of antimalarial drugs. This problem has since been aggravated by a decreased sensitivity of Plasmodium vivax to chloroquine. This review discusses strategies for evaluating the antimalarial activity of new compounds in vitro and in animal models ranging from conventional tests to the latest high-throughput screening technologies. Antimalarial discovery approaches include the following: the discovery of antimalarials from natural sources, chemical modifications of existing antimalarials, the development of hybrid compounds, testing of commercially available drugs that have been approved for human use for other diseases and molecular modelling using virtual screening technology and docking. Using these approaches, thousands of new drugs with known molecular specificity and active against P. falciparum have been selected. The inhibition of haemozoin formation in vitro, an indirect test that does not require P. falciparum cultures, has been described and this test is believed to improve antimalarial drug discovery. Clinical trials conducted with new funds from international agencies and the participation of several industries committed to the eradication of malaria should accelerate the discovery of drugs that are as effective as artemisinin derivatives, thus providing new hope for the control of malaria

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Section: Drug Combinations and Hybrids Used In Antimalarial Chemothermentioning

confidence: 99%

New approaches in antimalarial drug discovery and development: a review

Aguiar

Rocha

Souza

et al. 2012

Mem. Inst. Oswaldo Cruz

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“…The approaches currently being adopted to overcome the challenges of multi-drug resistance in P. falciparum include combination therapy, developing analogues of the existing drugs as well as drug resistance reversers [8]. In addition, molecular hybridization, which involves the rational design of new chemical entities by covalent fusion of two or more drugs, active compounds and/or pharmacophoric units with complimentary activities and multiple pharmacological targets, is an attractive strategy.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Azide-alkyne cycloaddition en route to 1 H -1,2,3-triazole-tethered 7-chloroquinoline-isatin chimeras: Synthesis and antimalarial evaluation

Raj

Singh

et al. 2013

European Journal of Medicinal Chemistry

122

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Please cite this article as: R. Raj, P. Singh, P. Singh, J. Gut, P.J. Rosenthal, V. Kumar, Azidealkyne cycloaddition en route to 1H-1,2,3-Triazole-tethered 7-chloroquinoline-isatin chimeras: Synthesis and antimalarial evaluation, European Journal of Medicinal Chemistry (2013), doi: 10.1016/ j.ejmech.2013 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPTAzide-alkyne cycloaddition en route to 1H-1,2,3-Triazole-tethered The compound 8h with an optimum combination of longer alkyl chain length and chloro substitutent at C-5 position of isatin ring displayed the best activity among the test compounds. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT Abstract:We describe the synthesis and antimalarial activities of 1H-1,2,3-triazole tethered 7-chloroquinolineisatin hybrids. Activity against cultured parasites was dependent on the C-5 substituent of the isatin ring as well as the alkyl chain length between the isatin and 7-chloroquinoline moieties. Compound 8h, with an optimum alkyl chain length (n=3) and a chloro substitutent at the C-5 position of the isatin ring, displayed the best activity among the test compounds, with IC 50 value of 1.21 µM against cultured W2-strain Plasmodium falciparum.

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“…For example, chloroquine (46) has been used for its antimalarial activity for more than 60 years; [56][57][58] bedaquiline (47), an inhibitor of the mycobacterial ATP synthase, has been approved to treat multi-drug resistant tuberculosis, [59] and cabozantinib (48), a multitargeted receptor tyrosine kinase inhibitor, showed effective anticancer activity and has been marketed for the treatment of medullary thyroid cancer ( Figure 4) Quinolines and their derivatives are important heterocyclic compounds because of their wide-ranging biological activities [52][53][54] and interesting photochemical properties [55]. For example, chloroquine (46) has been used for its antimalarial activity for more than 60 years; [56][57][58] bedaquiline (47), an inhibitor of the mycobacterial ATP synthase, has been approved to treat multi-drug resistant tuberculosis, [59] and cabozantinib (48), a multitargeted receptor tyrosine kinase inhibitor, showed effective anticancer activity and has been marketed for the treatment of medullary thyroid cancer ( Figure 4) [60]. Therefore, in the last decade, several new synthetic routes to quinoline derivatives under MW-irradiation have been reported [61][62][63][64][65][66].…”

Section: Quinolinesmentioning

confidence: 99%

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

et al. 2016

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This review describes the formation of six-membered heterocyclic compounds and their fused analogues under microwave activation using modern organic transformations including cyclocondensation, cycloaddition, multicomponents and other modular reactions. The review is divided according to the main heterocycle types in order of increasing complexity, starting with heterocyclic systems containing one, two and three heteroatoms and their fused analogues. Recent microwave applications are reviewed, with special focus on the chemistry of bioactive compounds. Selected examples from the 2006 to 2015 literature are discussed.

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Recent developments in the design and synthesis of hybrid molecules basedon aminoquinoline ring and their antiplasmodial evaluation

Cited by 146 publications

References 185 publications

New approaches in antimalarial drug discovery and development: a review

New approaches in antimalarial drug discovery and development: a review

Azide-alkyne cycloaddition en route to 1 H -1,2,3-triazole-tethered 7-chloroquinoline-isatin chimeras: Synthesis and antimalarial evaluation

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

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