4-Aminoquinoline-Pyrimidine hybrids: Synthesis, antimalarial activity, heme binding and docking studies

Kumar, Deepak; Khan, Shabana I.; Tekwani, Babu L.; Ponnan, Prija; Rawat, Diwan S.

doi:10.1016/j.ejmech.2014.10.061

Cited by 79 publications

(54 citation statements)

References 71 publications

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“…[23][24][25][26] General procedure for the synthesis of 4-aminoquinoline-pyrimidine hybrids (8a-x) The reaction mixture was then stirred overnight (14 h) at ambient temperature.…”

Section: Methodsmentioning

confidence: 99%

“…Currently, WHO recommends artemisininbased combination therapy (ACT) with a conventional antimalarial agent, particularly for infections caused by P. falciparum. Towards this end, we had previously reported 4-aminoquinoline based hybrids with folate inhibitor triazine [20][21][22] and pyrimidine [23][24][25][26] pharmacophores. The concept of molecular hybrids has shown promising results and may hold a key role en route to solving this menacing problem.…”

Section: Introductionmentioning

confidence: 99%

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4-Aminoquinoline-pyrimidine-aminoalkanols: synthesis, in vitro antimalarial activity, docking studies and ADME predictions

et al. 2015

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Twenty-four new 4-aminoquinoline-pyrimidine hybrids containing a terminal aliphatic amino-alcohol chain were synthesized and assessed for their antimalarial activity against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum. All of the compounds displayed potent antiplasmodial activities (IC 50 values in the range of 0.05-10.47 mM) with no appreciable cytotoxicity towards mammalian cells, up to the highest tested concentration of 12 mM. Molecular docking studies of the most active compounds (8b-8f, 8u and 8v) with both wild type and quadruple mutant Pf-DHFR-TSwere performed, which exhibited interactions comparable to conventional folate inhibitors. ADME predictions also revealed favourable pharmacokinetic parameters for the synthesized hybrids, which warrants their suitability for development as potent antimalarials.

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“…[23][24][25][26] General procedure for the synthesis of 4-aminoquinoline-pyrimidine hybrids (8a-x) The reaction mixture was then stirred overnight (14 h) at ambient temperature.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

4-Aminoquinoline-pyrimidine-aminoalkanols: synthesis, in vitro antimalarial activity, docking studies and ADME predictions

et al. 2015

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“…[1][2][3][4][5][6][7][8][9][10][11][12][13] In addition, pyrido [2,3-d]pyrimidines exhibit antimicrobial, antifungal, and anti-inflammatory activities, [14][15][16] while thieno [2,3-d]pyrimidines exhibit antiproliferative and anti-inflammatory activities. Pyrimidines and their related fused heterocyclic derivatives possess antibacterial, antifungal, antiviral, anti-influenza, antioxidant, anti-inflammatory, antimalarial, antiproliferative, and antitumor activities.…”

Section: Introductionmentioning

confidence: 99%

Efficient synthesis and molecular docking of novel antibacterial pyrimidines and their related fused heterocyclic derivatives

Sanad

Ahmed

Mekky

2019

Journal of Heterocyclic Chem

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3-(Benzo[d] [1,3]dioxol-5-yl)-1-(thiophen-2-yl)prop-2-en-1-one reacted with each of thiourea and 6-amino-2-thioxo-2,3-dihydropyrimidin-4(1H)-one to give the corresponding pyrimidine-2(1H)-thiones. Then, these compounds reacted with the appropriate hydrazonyl chlorides in dioxane in the presence of triethylamine to afford the corresponding [1,2,4]triazolo[4,3-a]pyrimidines and their related fused pyridines. Moreover, chalcone was cyclocondensed with 2-cyanothioacetamide to give pyridine-2(1H)-thione and taken as a key synthon to novel 2-(methylthio)pyridothienopyrimidin-4(3H)-one derivative. The above derivative reacted with the appropriate hydrazonyl chlorides in dioxane in the presence of triethylamine to yield the corresponding pyridothieno[3,2-d][1,2,4]triazolo[4,3-a]pyrimidines. Study of the in vitro antimicrobial activities of the newly pyrimidines were performed. Pyridothienopyrimidine 24a showed the highest inhibitory activity against all bacteria with MIC values of 3.9, 7.81, 7.81, and 15.62 μg/mL, respectively, against Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Streptococcus mutans, respectively, as compared to reference drugs. Molecular docking was studied to predict of the optimized conformation of pyrimidines as active ligands against the Escherichia coli alkaline phosphatase. The structures of the hybrid molecules were elucidated by IR, Mass, 1 H NMR, and 13 C NMR spectra as well as elemental analyses.

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“…These derivatives are also known as m -diazine or 1,3-diazone can be regarded as cyclic amine and shows the various biological activities i.e. antiviral [4, 5]; anticancer [6]; antimicrobial [7]; anti-inflammatory [8]; analgesic [9]; antioxidant [10]; antimalarial [11]. …”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and antimicrobial evaluation of pyrimidin-2-ol/thiol/amine analogues

Narwal

Kumar

Verma

2017

Chemistry Central Journal

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BackgroundPyrimidine is an aromatic heterocyclic moiety containing nitrogen atom at 1st and 3rd positions and play an important role to forms the central core for different necessity of biological active compounds, from this facts, we have designed and synthesized a new class of pyrimidin-2-ol/thiol/amine derivatives and screened for its in vitro antimicrobial activity.Results and discussionThe synthesized pyrimidine derivatives were confirmed by IR, 1H/13C-NMR, Mass spectral studies and evaluated for their in vitro antimicrobial potential against Gram positive (S. aureus and B. subtilis), Gram negative (E. coli, P. aeruginosa and S. enterica) bacterial strains and fungal strain (C. albicans and A. niger) by tube dilution method and recorded minimum inhibitory concentration in µM/ml. The MBC and MFC values represent the lowest concentration of compound that produces in the range of 96–98% end point reduction of the used test bacterial and fungal species.ConclusionIn general all synthesized derivatives exhibited good antimicrobial activity. Among them, compounds 2, 5, 10, 11 and 12 have significant antimicrobial activity against used bacterial and fungal strains and also found to be more active than the standard drugs.Graphical abstractPyrimidine is an aromatic heterocyclic moiety containing nitrogen atom at 1st and 3rd positions and play an important role to forms the central core for different necessity of biological active compounds, from this facts, we have designed and synthesized a new class of pyrimidin-2-ol/thiol/amine derivatives and screened for its in vitro antimicrobial activity. The synthesized pyrimidine derivatives were confirmed by IR, 1H/13C-NMR, Mass spectral studies and evaluated for their in vitro antimicrobial potential against Gram positive (S. aureus and B. subtilis), Gram negative (E. coli, P. aeruginosa and S. enterica) bacterial strains and fungal strain (C. albicans and A. niger) by tube dilution method and recorded minimum inhibitory concentration in µM/ml. The MBC and MFC values represent the lowest concentration of compound that produces in the range of 96–98% end point reduction of the used test bacterial and fungal species.

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4-Aminoquinoline-Pyrimidine hybrids: Synthesis, antimalarial activity, heme binding and docking studies

Cited by 79 publications

References 71 publications

4-Aminoquinoline-pyrimidine-aminoalkanols: synthesis, in vitro antimalarial activity, docking studies and ADME predictions

4-Aminoquinoline-pyrimidine-aminoalkanols: synthesis, in vitro antimalarial activity, docking studies and ADME predictions

Efficient synthesis and molecular docking of novel antibacterial pyrimidines and their related fused heterocyclic derivatives

Design, synthesis and antimicrobial evaluation of pyrimidin-2-ol/thiol/amine analogues

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