Design, Synthesis, and Antiplasmodial Activity of Hybrid Compounds Based on (2R,3S)-N-Benzoyl-3-phenylisoserine

An efficient and economically viable approach for the large-scale conversion of artemisinin into the antimalarial frontline drug artesunate was developed. This advanced synthesis includes an NaBH4-induced reduction, followed by an esterification with succinic anhydride under basic conditions. The entire conversion follows the principles of green chemistry, i.e., application of reusable solvents.Graphical abstract

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“…: 150–151 °C (Ref. [41], 152–153 °C). The spectroscopic data were found to be identical with the ones described in Refs.…”

Section: Resultsmentioning

confidence: 99%

A simplified and scalable synthesis of artesunate

2016

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“…Hybrids 101c and 101d were the most potent against W2 (IC 50 = 0.13 and 0.16 µM, respectively), but were still less active than CQ (IC 50 = 0.05 µM). These results suggested that the inherent antimalarial activity of the 4-amino-7-chloroquinoline was retained, but hybridization with (2R,3S)-N-benzoyl-3-phenylisoserine did not improve antimalarial potency as anticipated 185. …”

mentioning

confidence: 76%

Quinoline-based antimalarial hybrid compounds

Vandekerckhove

D’hooghe

2015

Bioorganic & Medicinal Chemistry

192

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Quinoline-containing compounds, such as quinine and chloroquine, have a long-standing history as potent antimalarial agents. However, the increasing resistance of the Plasmodium parasite against these drugs and the lack of licensed malaria vaccines have forced chemists to develop synthetic strategies toward novel biologically active molecules. A strategy that has attracted considerable attention in current medicinal chemistry is based on the conjugation of two biologically active molecules into one hybrid compound. Since quinolines are considered to be privileged antimalarial building blocks, the synthesis of quinoline-containing antimalarial hybrids has been elaborated extensively in recent years. This review provides a literature overview of antimalarial hybrid molecules containing a quinoline core, covering publications between 2009 and 2014.

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“…The (2 R ,3 S )‐ N ‐benzoyl‐3‐phenylisoserine‐quinoline hybrids 41 (IC 50 : 130‐1000 nM) showed considerable potency against CQR W2 and multidrug‐resistant K1 strains of P falciparum , but they were no superior to CQ (IC 50 : 50 and 340 nM) . The SAR indicated ester hybrids 41a ‐ d (IC 50 : 130‐390 nM) were more active than the amide analogs 41e , f (IC 50 : 360‐1000 nM).…”

Section: Quinoline Hybridized With Novel Antimalarial Pharmacophores mentioning

confidence: 99%

“…The SAR indicated ester hybrids 41a ‐ d (IC 50 : 130‐390 nM) were more active than the amide analogs 41e , f (IC 50 : 360‐1000 nM). Incorporation of 1,2,3‐triazole fragment between phenylisoserine and quinoline motif led to great loss of activity, and the IC 50 values for the majority of hybrids 42 were greater than 1000 nM …”

Section: Quinoline Hybridized With Novel Antimalarial Pharmacophores mentioning

confidence: 99%

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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Design, Synthesis, and Antiplasmodial Activity of Hybrid Compounds Based on (2R,3S)-N-Benzoyl-3-phenylisoserine

Cited by 33 publications

References 21 publications

A simplified and scalable synthesis of artesunate

A simplified and scalable synthesis of artesunate

Quinoline-based antimalarial hybrid compounds

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

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