N -Piperonyl substitution on aminoquinoline-pyrimidine hybrids: Effect on the antiplasmodial potency

Kholiya, Rohit; Khan, Shabana I.; Bahuguna, Aparna; Tripathi, Mohit; Rawat, Diwan S.

doi:10.1016/j.ejmech.2017.03.007

Cited by 17 publications

(9 citation statements)

References 45 publications

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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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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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“…4-aminoquinoline-piperonyl-pyrimidine hybrid compounds synthesized by Kholiya and coworkers were effective antimalarials with IC 50 values in the range of 0.02–5.16 µM. Some of the hybrids were eight-fold more active when compared to chloroquine [36]. The hybrid in which the chloro group on the pyrimidine was replaced with 4-ethyl piperazine was more active than amino-substituted hybrids.…”

Section: Combination Therapy Strategiesmentioning

confidence: 99%

“…Increasing the diamine spacer to three carbon atoms decreased the antimalarial activity of the hybrids. Hybrids containing ethylene diamine linkers were significantly active against strains of P. falciparum with IC 50 values in the range of 0.05–0.29 μM against resistant strain and 0.02–0.05 μM against sensitive strain [36].…”

Section: Combination Therapy Strategiesmentioning

confidence: 99%

Combination Therapy Strategies for the Treatment of Malaria

Alven

Aderibigbe

2019

Molecules

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Malaria is a vector- and blood-borne infection that is responsible for a large number of deaths around the world. Most of the currently used antimalarial therapeutics suffer from drug resistance. The other limitations associated with the currently used antimalarial drugs are poor drug bioavailability, drug toxicity, and poor water solubility. Combination therapy is one of the best approaches that is currently used to treat malaria, whereby two or more therapeutic agents are combined. Different combination therapy strategies are used to overcome the aforementioned limitations. This review article reports two strategies of combination therapy; the incorporation of two or more antimalarials into polymer-based carriers and hybrid compounds designed by hybridization of two antimalarial pharmacophores.

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“…Thus, hybridization is a practical approach to obtain novel compounds with antimalarial and anticancer activity. [ 14–27 ]…”

Section: Introductionmentioning

confidence: 99%

Synthesis and antimalarial and anticancer evaluation of 7‐chlorquinoline‐4‐thiazoleacetic derivatives containing aryl hydrazide moieties

Ramírez

Fernández

Rodrígues

et al. 2021

Archiv der Pharmazie

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Twelve 7‐chloroquinoline derivatives were designed and synthesized using the principle of molecular hybridization through the coupling of 2‐[2‐(7‐chloroquinolin‐4‐ylthio)‐4‐methylthiazol‐5‐yl]acetic acid 1 with various benzoyl hydrazines 2a–l. The synthetic compounds were tested as antimalarials. Some of them showed an efficient in vitro activity as inhibitors of β‐hematin formation and an in vivo activity in a murine model, resulting in compounds 8 and 9 as the most active ones with IC50 values of 0.65 ± 0.09 and 0.64 ± 0.16 µM, respectively. The effects of the compounds on the cell viability, cell cycle, and apoptosis induction of A549 and MCF‐7 cancer cell lines were also examined. Our data showed that compounds 6 and 12 were the most active agents, decreasing the cell viability of MCF‐7 cells with IC50 values of 15.41 and 12.99 µM, respectively. None of the compounds analyzed significantly affected the viability of peripheral blood mononuclear cells. Also, significant induction of apoptosis was observed when both cancer cell lines were incubated with compounds 6 and 12. In MCF‐7 cells, treatment with these compounds led to cell cycle arrest in the G0/G1 phase. The results obtained suggest that these structures may be useful in developing new therapies for malaria and cancer treatment.

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N -Piperonyl substitution on aminoquinoline-pyrimidine hybrids: Effect on the antiplasmodial potency

Cited by 17 publications

References 45 publications

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

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

Combination Therapy Strategies for the Treatment of Malaria

Synthesis and antimalarial and anticancer evaluation of 7‐chlorquinoline‐4‐thiazoleacetic derivatives containing aryl hydrazide moieties

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