949934-17-2Relevant academic research and scientific papers
Clotrimazole scaffold as an innovative pharmacophore towards potent antimalarial agents: Design, synthesis, and biological and structure-activity relationship studies
Gemma, Sandra,Campiani, Giuseppe,Butini, Stefania,Kukreja, Gagan,Coccone, Salvatore Sanna,Joshi, Bhupendra P.,Persico, Marco,Nacci, Vito,Fiorini, Isabella,Novellino, Ettore,Fattorusso, Ernesto,Taglialatela-Scafati, Orazio,Savini, Luisa,Taramelli, Donatella,Basilico, Nicoletta,Parapini, Silvia,Morace, Giulia,Yardley, Vanessa,Croft, Simon,Coletta, Massimiliano,Marini, Stefano,Fattorusso, Caterina
, p. 1278 - 1294 (2008/09/20)
We describe herein the design, synthesis, biological evaluation, and structure-activity relationship (SAR) studies of an innovative class of antimalarial agents based on a polyaromatic pharmacophore structurally related to clotrimazole and easy to synthesize by low-cost synthetic procedures. SAR studies delineated a number of structural features able to modulate the in vitro and in vivo antimalarial activity. A selected set of antimalarials was further biologically investigated and displayed low in vitro toxicity on a panel of human and murine cell lines. In vitro, the novel compounds proved to be selective for free heme, as demonstrated in the β-hematin inhibitory activity assay, and did not show inhibitory activity against 14-α-lanosterol demethylase (a fungal P450 cytochrome). Compounds 2, 4e, and 4n exhibited in vivo activity against P. chabaudi after oral administration and thus represent promising antimalarial agents for further preclinical development.
ANTIMALARIAL AGENTS HAVING POLYAROMATIC STRUCTURE
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Page/Page column 30, (2010/11/28)
Antimalarial agents having a novel pharmacophore of formula (I) are herein described. These polycyclic compounds are able to inhibit chloroquine-sensitive and chloroquine-resistant strains ofPlasmodium falciparum (Pf). Furthermore, the synthesis of these compounds involves few steps from commercial products with low cost of production.Λa présente invention concerne des agents antimalariaux comportant un nouveau pharmacophore de formule (I). Ces composés polycycliques sont susceptibles d''inhiber les souches sensibles à la chloroquine et résistantes à la chloroquine de Plasmodium falciparum (Pf). En outre, la synthèse de ces composés est peu onéreuse et implique peu d''étapes à partir des produits commerciaux.
