LitCovid-sentences  

PMC:7696151 / 1312-5131 JSONTXT 3 Projects

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Id Subject Object Predicate Lexical cue
T12 0-2 Sentence denotes 1.
T13 3-15 Sentence denotes Introduction
T14 16-181 Sentence denotes The 4-aminoquinolonehydroxychloroquine (HCQ) was synthesized for the first time in 1946, but its history began as far back as the 1600s thanks to the Incas in Chile.
T15 182-404 Sentence denotes They introduced the special properties of cinchona bark to the Jesuits and in 1820 quinine and cinchonine were isolated and identified as the main alkaloids responsible for the antimalarial activity attributed to the bark.
T16 405-499 Sentence denotes For these reasons, in 1900, the Dutch and British transplanted this “miraculous tree” to Java.
T17 500-597 Sentence denotes The quinine soon began to be also used for the treatment of systemic lupus erythematosus [1,2,3].
T18 598-729 Sentence denotes The increasing need for quinine, due to malaria diffusion, led the pharmaceutical industry to the creation of a synthetic molecule.
T19 730-793 Sentence denotes In 1934 Johann (Hans) Andersag and co-workers at the Bayer I.G.
T20 794-937 Sentence denotes Farbenindustrie in Elberfeld laboratories, Germany, synthesized chloroquine (CQ) for the first time, judged by the Germans to be too toxic [4].
T21 938-1063 Sentence denotes However, the production of natural quinine was blocked by the Japanese army’s occupation of Java during the Second World War.
T22 1064-1162 Sentence denotes Therefore, it was necessary to deepen the studies on molecules that could replace natural quinine.
T23 1163-1344 Sentence denotes The Americans soon synthesized from CQ the HCQ, which resulted in it being less toxic than its ancestor so that in 1955 the scientific community proposed it as an alternative to CQ.
T24 1345-1422 Sentence denotes Figure 1 represents the historical development that led to HCQ synthesis [5].
T25 1423-1678 Sentence denotes This molecule, which has always been known as antimalarial, has come back into vogue in recent months due to the ongoing new coronavirus (2019-nCoV, or COVID-19 or 2019-nCo) worldwide pandemic, that causes a severe acute respiratory syndrome (SARS-CoV-2).
T26 1679-1861 Sentence denotes In fact, several research groups have evaluated the use of CQ (C18H26ClN3) and in particular its derivative HCQ (C18H26ClN3O), as a promising treatment for COVID-19 patients [6,7,8].
T27 1862-2070 Sentence denotes CQ and HCQ have a core structure consisting of two aromatic rings fused, the 4-aminoquinoline nucleus, and an amphiphilic weak basic side chain (represented in green and red colors in Figure 1, respectively).
T28 2071-2207 Sentence denotes The two chemical structures differ only for the hydroxyl group at the end of N-ethyl side chain (represented in blue color in Figure 1).
T29 2208-2402 Sentence denotes These are water-soluble molecules and, for their chemical nature, can pass the cell membranes; however, the presence of the hydroxyl group in the HCQ makes it more polar and less lipophilic [8].
T30 2403-2555 Sentence denotes Moreover, the accumulation of CQ and HCQ in intracellular compartments is due principally to the side chain and both have enantiomers (R and S isomers).
T31 2556-2660 Sentence denotes Researches also demonstrated that the R-HCQ is present in the blood at higher concentrations than S-HCQ.
T32 2661-2753 Sentence denotes These results suggested the stereoselective processes in the metabolism of the molecule [9].
T33 2754-2960 Sentence denotes Studies of structure-activity relationships have demonstrated that the halogen substitutions of different 4-aminoquinolinesderivatives reduced the toxicity, but it also reduced the pharmacological activity.
T34 2961-3064 Sentence denotes Instead, the therapeutic ratio is decreased by substitution of the alkyl side chain with an aryl chain.
T35 3065-3205 Sentence denotes Nevertheless, the therapeutic ratio decreases and toxicity increases with an increase of the alkyl side-chain length above 5 carbons [7,10].
T36 3206-3348 Sentence denotes Usually, CQ and HCQ are administered as phosphate and sulphate salts, respectively, and both drugs are absorbed in the upper intestinal tract.
T37 3349-3435 Sentence denotes However, clinically, HCQ is more frequently used than CQ for its lesser toxicity [11].
T38 3436-3626 Sentence denotes Both molecules give mild nausea, stomach cramps, gastrointestinal upset, and mild diarrhoea as adverse effects and long-term usage determines loss of retinal function and severe retinopathy.
T39 3627-3819 Sentence denotes These drugs are used, to date, in malaria patients and in several inflammatory diseases like rheumatoid arthritis, Sjögren syndrome, dermatomyositis, and systemic lupus erythematosus [7,8,10].