N-Substituted aminoquinoline-pyrimidine hybrids: Synthesis, in vitro antimalarial activity evaluation and docking studies

Maurya, Shiv Shyam; Bahuguna, Aparna; Khan, Shabana I.; Kumar, Deepak; Kholiya, Rohit; Rawat, Diwan S.

doi:10.1016/j.ejmech.2018.11.021

Cited by 46 publications

(26 citation statements)

References 28 publications

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“…pyrimethamine [15], quinazoline derivatives [16] and 2,4-diamino-5-(2'arylpropargyl) pyrimidine derivatives as antifolate [17]. The invention can also be targeted for hybrid compounds [18][19].…”

Section: ■ Introductionmentioning

confidence: 99%

Docking of New Designed Compounds Derived from 1,6-Dihydro-1,3,5-triazine-2,4-diamine Toward Quadruple Mutant Plasmodium Dihydrofolate Reductase

2019

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Resistance to the traditional antifolates is now widespread in Plasmodium falciparum and Plasmodium vivax. To find the interaction model of some compounds derived from 1,6-dihydro-1,3,5-triazine-2,4-diamine, molecular docking technique was carried out using these compounds ligand and pDHFR as the receptor. Complex ligand and the receptor from Protein Data Bank (PDB ID 1J3K) were chosen as an interaction model between a ligand and its receptor. Each compound was optimized using ab initio methods with 6-311G basis set. Partial charges of ligand were added using AM1-BCC methods. Each ligand was docked to the receptor utilizing Dock6 software. Theoretical prediction based on the binding energy between these compounds as the ligand with pDHFR as receptor resulted in 1 compound, namely 6,6-dimethyl-1-[3-(2-chloro-4,5-dibromophenoxy)propoxy]-1,6-dihydro-1,3,5-triazine-2,4-diamine possessing binding affinity better than that of WR99210 which was known to have good antimalarial activity.

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Section: ■ Introductionmentioning

confidence: 99%

Docking of New Designed Compounds Derived from 1,6-Dihydro-1,3,5-triazine-2,4-diamine Toward Quadruple Mutant Plasmodium Dihydrofolate Reductase

2019

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“…Replacement of chloro at pyrimidine by nitrogen‐containing heterocycles ( 118 and 199 ) could increase the activity against CQR Dd2 strain to some extent, but aminoalkanols reduced the activity . Similar SARs were also observed for quinoline‐pyrimidine hybrids 120 to 122 (IC 50 : 120‐440, 140‐240, and 5‐30 nM against CQS 3D7 strain, respectively; 500‐700, 580‐1,170, and 16‐210 nM against CQR Dd2 strain, respectively), quinoline‐pyrimidine hybrids 123 to 130 ( 123 and 124 attaching furan skeleton, IC 50 : 38‐61 and 39‐257 nM against CQS 3D7 and CQR Dd2 strains, respectively; 125 and 126 with piperonyl fragment, IC 50 : 20‐150 and 50‐990 nM against CQS 3D7 and CQR Dd2 strains, respectively; 127 and 128 with pyridine motif, IC 50 : 30‐1193 and 39‐1143 nM against CQS 3D7 and CQR Dd2 strains, respectively; 129 and 130 with thiophene motif, IC 50 : 32.8‐83.7 and 18.9‐409.1 nM against CQS 3D7 and CQR Dd2 strains, respectively) bearing an aromatic ring at the amino near to pyrimidine moiety, and quinoline‐pyrimidine hybrids 131 (IC 50 : 32‐204 and 32‐1018 nM against CQS 3D7 and CQR Dd2 strains, respectively), 132 (IC 50 : 19‐6022 and 46‐9994 nM against CQS 3D7 and CQR Dd2 strains, respectively) incorporating modified anilines at the pyrimidine end. Furthermore, for hybrids 122 , the relative contribution order of nitrogen‐containing heterocycles at pyrimidine moiety was 4‐ethyl piperazine > 4‐methyl piperazine > morpholine > piperidine.…”

Section: Quinoline Hybridized With Novel Antimalarial Pharmacophores mentioning

confidence: 61%

Hybrid molecules with potential in vitro antiplasmodial and in vivo antimalarial activity against drug‐resistant Plasmodium falciparum

Feng

Chang

et al. 2019

Medicinal Research Reviews

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Malaria is a tropical disease, leading to around half a million deaths annually. Antimalarials such as quinolines are crucial to fight against malaria, but malaria control is extremely challenged by the limited pipeline of effective pharmaceuticals against drug-resistant strains of Plasmodium falciparum which are resistant toward almost all currently accessible antimalarials. To tackle the growing resistance, new antimalarial drugs are needed urgently. Hybrid molecules which contain two or more pharmacophores have the potential to overcome the drug resistance, and hybridization of quinoline privileged antimalarial building block with other antimalarial pharmacophores may provide novel molecules with enhanced in vitro and in vivo activity against drug-resistant (including multidrug-resistant) P falciparum. In recent years, numerous of quinoline hybrids were developed, and their activities against a panel of drug-resistant P falciparum strains were screened. Some of quinoline hybrids were found to possess promising in vitro and in vivo potency. This review emphasized quinoline hybrid molecules with

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“…In addition, various ADME parameters of the synthesized derivatives were calculated to better understand the effect of physicochemical and pharmacokinetic properties on their bioavailability in human bodies [24,25]. The results (Table 2)…”

Section: In Silico Adme Predictive Studymentioning

confidence: 99%

Design and synthesis of new 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs as Mycobacterium tuberculosis DNA gyrase inhibitors

et al. 2021

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Background Tuberculosis is evidently a major health threat among human populations worldwide. The current study presents the synthesis of new 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs (4a–o) as potential Mycobacterium tuberculosis DNA gyrase inhibitors. DNA gyrase regulates DNA topology in MTB and has been a target of choice for antibacterial therapy. With this in mind, the synthesized derivatives (4a–o) were subjected to in vitro antitubercular evaluation by the MABA method and were tested for MTB DNA gyrase inhibition by supercoiling assay. Results All the synthesized compounds displayed inhibition of MTB within the MIC range of 1.56–12.5 μM. Further, out of the selected compounds that underwent DNA gyrase inhibition, compound 4o proved to be a potent lead molecule by displaying 82% of enzyme inhibition at 1 μM. All the synthesized derivatives also underwent molecular docking studies to comprehend their hypothetical binding interactions with Mycobacterium smegmatis GyrB. Conclusion All the results suggested that most of the synthesized derivatives inhibited Mycobacterium tuberculosis, and some 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs could act as leads for the development of antitubercular agents.

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N-Substituted aminoquinoline-pyrimidine hybrids: Synthesis, in vitro antimalarial activity evaluation and docking studies

Cited by 46 publications

References 28 publications

Docking of New Designed Compounds Derived from 1,6-Dihydro-1,3,5-triazine-2,4-diamine Toward Quadruple Mutant Plasmodium Dihydrofolate Reductase

Docking of New Designed Compounds Derived from 1,6-Dihydro-1,3,5-triazine-2,4-diamine Toward Quadruple Mutant Plasmodium Dihydrofolate Reductase

Hybrid molecules with potential in vitro antiplasmodial and in vivo antimalarial activity against drug‐resistant Plasmodium falciparum

Design and synthesis of new 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs as Mycobacterium tuberculosis DNA gyrase inhibitors

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