Identification of 2-arylquinazolines with alkyl-polyamine motifs as potent antileishmanial agents: synthesis and biological evaluation studies

Kumari, A.; Jaiswal, Tara; Kumar, Vinay; Hura, Neha; Kumar, Gulshan; Babu, Neerupudi Kishore; Acharya, Ayan; Roy, Pradyot Kumar; Guchhait, Sankar K.; Singh, Sushma

doi:10.1039/d1md00336d

Cited by 7 publications

(1 citation statement)

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“…Upon treatment with 2X IC 50 of compound 9 b , the cell membrane integrity was completely lost and few of the cells had lysed. In the Miltefosine treated cells, which was used as a positive control, the cells appeared swollen [6e,25] …”

Section: Resultsmentioning

confidence: 99%

A Core‐Linker‐Polyamine (CLP) Strategy Enables Rapid Discovery of Antileishmanial Aminoalkylquinolinecarboxamides That Target Oxidative Stress Mechanism

et al. 2022

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A Core‐Linker‐Polyamine (CLP) strategy has been exploited to develop new antileishmanial agents. It involves the linker‐based assembly of alkyl‐polyamine side chain as a potential pharmacophore motif with a privileged heterocyclic motif, 4‐arylquinoline. A series of aminoalkyl 4‐arylquinoline‐2‐carboxamides and their analogs were synthesized and tested against L. donovani promastigotes. Among all synthesized derivatives, 10 compounds showed significant antipromastigote activities with more efficacy (IC50: 4.75–8 μM) than an antileishmanial oral drug Miltefosine (IC50: 8.9±1.55 μM). Most active aminoalkyl‐quinoline‐carboxamides 9 a and 9 b, displayed negligible cytotoxicity towards human monocytic (THP‐1) macrophages. The compounds show antileishmanial activity by generating mitochondrial superoxide radicals. However, they did not show interference with trypanothione reductase, a redox enzyme of Leishmania. Significant change in the morphology of the L. donovani promastigote by the compounds was observed. The Structure‐activity relationship analysis suggest the pharmacophoric importance of alkylpolyamine and carboxamide motifs. In silico evaluation indicated that the investigated active molecules 9 a and 9 b possess important drug‐likeness, physicochemical and pharmacokinetic‐relevant properties.

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Section: Resultsmentioning

confidence: 99%

A Core‐Linker‐Polyamine (CLP) Strategy Enables Rapid Discovery of Antileishmanial Aminoalkylquinolinecarboxamides That Target Oxidative Stress Mechanism

et al. 2022

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Pyridoxal kinase gene deletion leads to impaired growth, deranged redox metabolism and cell cycle arrest in Leishmania donovani

Roy,

Paul,

Lalchhuanawmi

et al. 2024

Biochimie

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The role of natural anti-parasitic guided development of synthetic drugs for leishmaniasis

Pal¹,

Teli²,

Matada³

2023

European Journal of Medicinal Chemistry

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Identification of 2-arylquinazolines with alkyl-polyamine motifs as potent antileishmanial agents: synthesis and biological evaluation studies

Abstract: 2-Arylquinazolines with a range of alkyl polyamines as side chain/ring functional motifs at 4th-position were considered for antileishmanial study with the rationale that related heterocyclic scaffolds and the polyamine functionalities...

Cited by 7 publications

References 45 publications

A Core‐Linker‐Polyamine (CLP) Strategy Enables Rapid Discovery of Antileishmanial Aminoalkylquinolinecarboxamides That Target Oxidative Stress Mechanism

A Core‐Linker‐Polyamine (CLP) Strategy Enables Rapid Discovery of Antileishmanial Aminoalkylquinolinecarboxamides That Target Oxidative Stress Mechanism

Pyridoxal kinase gene deletion leads to impaired growth, deranged redox metabolism and cell cycle arrest in Leishmania donovani

The role of natural anti-parasitic guided development of synthetic drugs for leishmaniasis

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