Synthesis, characterization and antimalarial activity of quinoline–pyrimidine hybrids

Pretorius, Stefan I.; Breytenbach, Wilma; Kock, Carmen de; Smith, Peter J.; N’Da, David D.

doi:10.1016/j.bmc.2012.10.019

Cited by 91 publications

(44 citation statements)

References 43 publications

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“…Additionally, the nature of the linker employed can also contribute to the solubility of the entire unit. For example, the linker employed in chloroquinepyrimethamine hybrids has two ethylene oxide units, which take part in hydrogen bonding with the water molecules and most likely contribute to its good solubility in both acidic and neutral media (27).…”

Section: Advantages Of Hybridsmentioning

confidence: 99%

“…Here, one should consider the fact that the strategy employed in forming a hybrid would add bulk to the molecule, which might hinder its passage into the parasite cell, which in turn would lead to reduced penetration and suppressed activity. Pretorius et al (27) investigated this issue to ascertain the advantages of hybrids over equimolar combinations, in terms of antimalarial activity. They concluded that there were none.…”

Section: Which Are More Efficacious: Hybrids or Combinations?mentioning

confidence: 99%

“…Similarly, the two most potent hybrids from a series of quinoline-pyrimidine hybrids evaluated by Pretorius et al (27) contained rigid aromatic and piperazine linkers. This indicates that the flexibility of the linker between the two pharmacophores does not govern the activity of these compounds.…”

Section: Linker Selectionmentioning

confidence: 99%

See 2 more Smart Citations

Are Antimalarial Hybrid Molecules a Close Reality or a Distant Dream?

Agarwal

Gupta

Awasthi

2017

Antimicrob Agents Chemother

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Emergence of drug-resistant Plasmodium falciparum strains has led to a situation of haste in the scientific and pharmaceutical communities. Hence, all their efforts are redirected toward finding alternative chemotherapeutic agents that are capable of combating multidrug-resistant parasite strains. In light of this situation, scientists have come up with the concept of hybridization of two or more active pharmacophores into a single chemical entity, resulting in "antimalarial hybrids." The approach has been applied widely for generation of lead compounds against deadly diseases such as cancer and AIDS, with a proven potential for use as novel drugs, but is comparatively new in the sphere of antimalarial drug discovery. A sudden surge has been evidenced in the number of studies on the design and synthesis of hybrids for treating malaria and may be regarded as proof of their potential advantages over artemisinin-based combination therapy (ACT). However, it is evident from recent studies that most of the potential advantages of antimalarial hybrids, such as lower toxicity, better pharmacokinetics, and easier formulation, have yet to be realized. A number of questions left unaddressed at present need to be answered before this approach can progress to the late stages of clinical development and prove their worth in the clinic. To the best of our knowledge, this compilation is the first attempt to shed light on the shortcomings that are surfacing as more and more studies on molecular hybridization of the active pharmacophores of known antimalarials are being published.

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Section: Advantages Of Hybridsmentioning

confidence: 99%

Section: Which Are More Efficacious: Hybrids or Combinations?mentioning

confidence: 99%

See 1 more Smart Citation

Are Antimalarial Hybrid Molecules a Close Reality or a Distant Dream?

Agarwal

Gupta

Awasthi

2017

Antimicrob Agents Chemother

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“…Fused chromenes compounds possesses wide spectrum of activities such as antibacterial [1], anticancer agents [2], anti-rhinovirus activity [3], antipyretic, analgesic, anti-inflammatory and antioxidant activities [4]. Pyrimidines are an important class of the heterocyclic compounds possesses various therapeutic and pharmacological properties, like anti-inflammatory and antimicrobial agents [5], anticancer agents [6], antitubercular and antimicrobial activities [7] and antimalarial activity [8].…”

Section: Introductionmentioning

confidence: 99%

Zinc Triflate Promoted General Synthetic Protocol for the Facile Construction of Chromenes and Pyrimidines Bearing N-Allyl Quinolone Nucleus

Vala

Jardosh²,

Patel

2015

ILCPA

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A series of 8 derivatives of chromene 5a-h synthesized via one-pot cyclocondensation reaction of N-allyl quinolones, α/β naphthol and malononitrile. And 8 derivatives of pyrimidines 8a-h bearing N-allyl quinolone have been synthesized by N-allyl quinolones, ethylacetoacetate, thiourea/urea in the presence of zinc triflate as less toxic catalyst. This methodology allowed the high conversion of product at room temperature. Titled derivatives were elucidated by FT-IR, 1 H NMR, 13 C NMR, elemental analysis, and mass spectral data.

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“…They possess valuable biological activities such as cardiovascular [3], anti-HIV [4], anti-tumour [5], antiinflammatory [6], anti-tubercular [7], diuretic [8], antimicrobial [9] anti-cancer [9] and antimalarial [10]. Spectroscopic data was applied for predicting the ground state configuration and QSAR and QPR study of chalcones [11], oxazines [12], pyrazoline [13], imines [14], acyl halides, and it esters [15].…”

Section: Introductionmentioning

confidence: 99%