From Chloroquine to Antineoplastic Drugs? The Story of Antibacterial Quinolones

Rádl, S.

doi:10.1002/ardp.19963290302

Cited by 17 publications

(7 citation statements)

References 17 publications

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“…CQ was synthesized for the first time by H. Andersag in Bayer laboratories in Elberfeld in 1934 [17]. Initially studied also in vivo for its antimalarial activity, was abandoned in favor of quinacrine hydrochloride, a less toxic molecule [17,18]. Rediscovered in America during the Second World War, it was marketed in 1947 [17,[19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

“…Rediscovered in America during the Second World War, it was marketed in 1947 [17,[19][20][21][22][23]. Its structural formula derives from a molecule of natural origin, quinine, from which it differs for the substituents at position 6 and the position linked to chain 4 [17,18]. Although CQ was used for many years as both antimalarial prophylaxis and therapy, its use has been significantly reduced due to the onset of resistance, especially in Plasmodium falciparum [24].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

New Anti SARS-Cov-2 Targets for Quinoline Derivatives Chloroquine and Hydroxychloroquine

Gentile

Fuochi

Rescifina

et al. 2020

IJMS

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The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a severe global health crisis. In this paper, we used docking and simulation methods to identify potential targets and the mechanism of action of chloroquine (CQ) and hydroxychloroquine (HCQ) against SARS-CoV-2. Our results showed that both CQ and HCQ influenced the functionality of the envelope (E) protein, necessary in the maturation processes of the virus, due to interactions that modify the flexibility of the protein structure. Furthermore, CQ and HCQ also influenced the proofreading and capping of viral RNA in SARS-CoV-2, performed by nsp10/nsp14 and nsp10/nsp16. In particular, HCQ demonstrated a better energy binding with the examined targets compared to CQ, probably due to the hydrogen bonding of the hydroxyl group of HCQ with polar amino acid residues.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New Anti SARS-Cov-2 Targets for Quinoline Derivatives Chloroquine and Hydroxychloroquine

Gentile

Fuochi

Rescifina

et al. 2020

IJMS

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“…The good to excellent absorption and increased potency against Gram-negative bacteria has permitted the use of these compounds for treatment of systemic infections. Their potency against Gram-positive cocci is enhanced compared to the non-fluorinated quinolone agents, but their activity against Staphylococcus aureus and Streptococcus pneumoniae is modest, and extensive usage has resulted in rapid emergence of resistance in these organisms (3,6).…”

Section: Fluoroquinolone Classificationmentioning

confidence: 99%

“…The prototype quinolone antibiotic, nalidixic acid, was serendipitously discovered at the Sterling-Winthrop laboratories, New York, during the synthesis of antimalarial agents in the early 1960s (2). Nalidixic acid possessed moderate activity against Gramnegative aerobic enteric rods, but lacked useful activity against Gram-positive cocci, Pseudomonas aeruginosa, and anaerobic bacteria (3). Nalidixic acid was first introduced in the United States in 1963 for the treatment of urinary tract infections.…”

Section: Introductionmentioning

confidence: 99%

The fluoroquinolones: How long will their utility last?

Bakken

2004

Scandinavian Journal of Infectious Diseases

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Injudicious use of the fluoroquinolones may result in treatment failure, increased patient morbidity, increased health care cost, and possible patient fatality. Fluoroquinolone-resistant bacteria may also adversely impact the microbiological environment in the hospital, the local community and eventually large geographical regions. Fluoroquinolone resistance develops in a stepwise fashion, and current susceptibility testing methods and recommended MIC susceptible breakpoint values for the United States may fail to identify some bacteria that are resistant due to first step mutations at the fluoroquinolone target site gene sequences. C-8 methoxy- fluoroquinolone compounds are more active against resistant bacteria than the older compounds. Fluoroquinolone resistance relates directly to human and veterinary usage and emerging bacterial resistance poses the single greatest threat to the future survival of the fluoroquinolone drugs as an antibiotic class.

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“…Based on these results, the design of antimalarial drugs has been envisaged based on the 4-aminoquinoline 4 cores and a search for new antimalarial agents with the chloroquine-related core has continued to be actively pursued. [16][17][18] Due to the appearance of resistance to chloroquine, other chloroquine-related antimalarial drugs with quinoline motifs have been proposed. 19,20 Examples include amodiaquine (II) (trade names Camoquin, Flavoquine) 21 and amopyroquine (III) 22 , both of which contain a 4-aminoquinoline core.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, β-haematin inhibition, and in vitro antimalarial testing of isocryptolepine analogues: SAR study of indolo[3,2-c]quinolines with various substituents at C2, C6, and N11

Wang

Wicht

Imai

et al. 2014

Bioorganic & Medicinal Chemistry

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A series of indolo[3,2-c]quinolines were synthesized by modifying the side chains of the ω-aminoalkylamines at the C6 position and introducing substituents at the C2 position, such as F, Cl, Br, Me, MeO and NO2, and a methyl group at the N11 position for an SAR study. The in vitro antiplasmodial activities of the derivative agents against two different strains (CQS: NF54 and CQR: K1) and the cytotoxic activity against normal L6 cells were evaluated. The test results showed that compounds 6k and 6l containing the branched methyl groups of 3-aminopropylamino at C6 with a Cl atom at C2 exhibited a very low cytotoxicity with IC50 values above 4000 nM, high antimalarial activities with IC50 values of about 11 nM for CQS (NF54), IC50 values of about 17 nM for CQR (K1), and RI resistance indices of 1.6. Furthermore, the compounds were tested for β-haematic inhibition, and QSAR revealed an interesting linear correlation between the biological activity of CQS (NF54) and three contributing factors, namely solubility, hydrophilic surface area, and β-haematin inhibition for this series. In vivo testing of 6l showed a reduction in parasitaemia on day 4 with an activity of 38%.

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From Chloroquine to Antineoplastic Drugs? The Story of Antibacterial Quinolones

Abstract: Chemotherapy has not only proved valuable in treating many diseases but the history of discovery of some drugs makes exciting reading. The aim of this article is to outline one such story.

Cited by 17 publications

References 17 publications

New Anti SARS-Cov-2 Targets for Quinoline Derivatives Chloroquine and Hydroxychloroquine

New Anti SARS-Cov-2 Targets for Quinoline Derivatives Chloroquine and Hydroxychloroquine

The fluoroquinolones: How long will their utility last?

Synthesis, β-haematin inhibition, and in vitro antimalarial testing of isocryptolepine analogues: SAR study of indolo[3,2-c]quinolines with various substituents at C2, C6, and N11

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