Antimalarial Activity and Toxicity of a Metabolic Derivative of Quinine

Kelsey, F. E.; Oldham, Frances K.; Cantrell, William; Geiling, E. M. K.

doi:10.1038/157440a0

Cited by 7 publications

(6 citation statements)

References 3 publications

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“…Due to its low price, parenteral administration, and high efficacy against P. falciparum , it was widely used to treat malaria worldwide . To meet the needs of this compound in southeast Asia during World War II, the synthesis of 1 was promoted and completed, and some derivatives were developed with better potency and lower toxicity . In 2006, WHO stopped recommending 1 as a first‐line treatment for malaria, because of its high toxicity and the developing resistance of Plasmodium sp.…”

Section: Bioactivities Of Quinoline and Quinazoline Alkaloidsmentioning

confidence: 99%

“…166,167 To meet the needs of this compound in southeast Asia during World War II, the synthesis of 1 was promoted and completed, and some derivatives were developed with better potency and lower toxicity. 168–171 In 2006, WHO stopped recommending 1 as a first-line treatment for malaria, because of its high toxicity and the developing resistance of Plasmodium sp. However, it has still been used when artemisinins are not available.…”

Section: Bioactivities Of Quinoline and Quinazoline Alkaloidsmentioning

confidence: 99%

“…Among these compounds, 141 was the most active (MIC 12.5 M). Quinolone alkaloid 129, its N-methyl congener (144), and 2,3-dimethyl-4-quinolone(168) (Fig. 17)from Boronia bowmanii exhibited moderate antibacterial activity against Bacillus subtilis, Staphylocccus aureus, Sarcina lutea, exterotoxigenic E. coli, Salmonella typhi, and Klebsiella sp 226.…”

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Biologically active quinoline and quinazoline alkaloids part I

Shang

Morris‐Natschke

Liu

et al. 2017

Medicinal Research Reviews

320

166

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Quinoline and quinazoline alkaloids, two important classes of N-based heterocyclic compounds, have attracted tremendous attention from researchers worldwide since the 19th century. Over the past 200 years, many compounds from these two classes were isolated from natural sources, and most of them and their modified analogs possess significant bioactivities. Quinine and camptothecin are two of the most famous and important quinoline alkaloids, and their discoveries opened new areas in antimalarial and anticancer drug development, respectively. In this review, we survey the literature on bioactive alkaloids from these two classes and highlight research achievements prior to the year 2008 (Part I). Over 200 molecules with a broad range of bioactivities, including antitumor, antimalarial, antibacterial and antifungal, antiparasitic and insecticidal, antiviral, antiplatelet, anti-inflammatory, herbicidal, antioxidant and other activities, were reviewed. This survey should provide new clues or possibilities for the discovery of new and better drugs from the original naturally occurring quinoline and quinazoline alkaloids.

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Section: Bioactivities Of Quinoline and Quinazoline Alkaloidsmentioning

confidence: 99%

Section: Bioactivities Of Quinoline and Quinazoline Alkaloidsmentioning

confidence: 99%

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Biologically active quinoline and quinazoline alkaloids part I

Shang

Morris‐Natschke

Liu

et al. 2017

Medicinal Research Reviews

320

166

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“…Particularly, Qn has been attractive because of its medicinal effect in addition to the above‐mentioned aspects. Namely, Qn has been used as an effective antimalaria drug, which works by inhibiting crystallization of heme into hemozoin in the digestive vacuole of Plasmodium falciparum (malaria parasite) 6. 7…”

Section: Introductionmentioning

confidence: 99%

Crystal Structure of Quinine: The Effects of Vinyl and Methoxy Groups on Molecular Assemblies of Cinchona Alkaloids Cannot Be Ignored

Hisaki

Hiraishi

Sasaki

et al. 2012

Chemistry An Asian Journal

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Quinine, one of Cinchona alkaloids, has been of great interest from medical, synthetic, and supramolecular viewpoints. However, unaccountably, the guest-free (GF) crystal of quinine containing no solvent or other molecules has not been reported for nearly three decades, although GF crystals of other Cinchona alkaloids, such as quinidine, cinchonidine, and cinchonine, are already known. In this study, we successfully revealed the crystal structure of quinine, which belongs to the P2(1) space group with the cell parameters of a=6.0587(1), b=19.2492(5), c=22.2824(7) Å, β=92.1646(11)°, and V=2596.83(12) Å(3). Interestingly, the crystal has three crystallographically independent molecules in the cell (Z'=3) that are connected through a N(quinoline)⋅⋅⋅H-O hydrogen bond to form a pseudo three-two-fold (3(2)) double-helical motif. The helical motif is completely different from those observed in GF crystals of other Cinchona alkaloids. Hierarchical comparison on the crystal structures of a series of Cinchona alkaloids including quinine clearly demonstrated that only small structural differences of a molecule, particularly the position of the vinyl group, cause a significant variety of assembly manner in the crystalline state. There have been no reports systematically demonstrating such steric effect in crystals of Cinchona alkaloids, and, therefore, the present system contributes to the design of desired functional crystal structures.

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“…In a previous publication (Marshall, 1945a) we reported that quinine degradation product (QDP) showed no antimalarial action against Plasmodium gallinaceum in young chicks, when given orally in amounts equivalent to an active dose of quinine. Subsequently, Kelsey, Oldham, Cantrell & Geiling (1946) reported that, when given intravenously, the compound showed one third to one fifth the activity of quinine against chick malaria, and less than one twentieth that of quinine against P. lophurae when given orally to ducks. Pointing out that QDP was less toxic than quinine, thus making its therapeutic index nearly equal to that of quinine, these workers disagreed with our view that the metabolism of quinine results in an inherently less efficient drug.…”

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confidence: 99%