A library of 1H-1,2,3-triazole-tethered 4-aminoquinoline-benzoxaborole hybrids as well as aryl substituted benzoxaborole analogues was synthesized and screened for their anti-plasmodial efficacy against both chloroquine-susceptibility 3D7 and chloroquine-resistant W2 strains of P. falciparum. The inclusion of quinoline core among the synthesized analogues resulted in substantial enhancement of anti-plasmodial activities.
Carboxamides bearing sulphonamide functionality have been shown to exhibit significant lethal effect on Plasmodium falciparum, the causative agent of human malaria. Here we report the synthesis of thirty-two new drug-like sulphonamide pyrolidine carboxamide derivatives and their antiplasmodial and antioxidant capabilities. In addition, molecular docking was used to check their binding affinities for homology modelled P. falciparum N-myristoyltransferase, a confirmed drug target in the pathogen.
Antimalarial agents used as monotherapy are increasingly ineffective due to the emergence of Plasmodium resistant strains. Artemisinin (Arte), extracted from Artemisia annua, presents a good efficiency against the Plasmodium strains and is currently used to treat malaria. To avoid the appearance of new resistant strains to artemisinin, the use of Artemisinin-based Combination Therapy (ACT) with another antimalaria agent was recommended by WHO to provide an effective cure and delayed resistance.
Plasmodium parasites rely heavily on glycolysis for ATP production and for precursors for essential anabolic pathways, such as the methylerythritol phosphate (MEP) pathway. Here, we show that mutations in the Plasmodium falciparum glycolytic enzyme, phosphofructokinase (PfPFK9), are associated with in vitro resistance to a primary sulfonamide glycoside (PS-3).
Malaria is still a life-threatening public health issue, and the upsurge of resistant strains requires continuous generation of active molecules. In this work, 35 sulfonylhydrazone derivatives were synthesized and evaluated against Plasmodium falciparum chloroquine-sensitive (3D7) and resistant (W2) strains.
The discovery and development of multistage antimalarial drugs targeting intra-erythrocytic asexual and sexual Plasmodium falciparum parasites is of utmost importance to achieve the ambitious goal of malaria elimination. Here, we report the validation of naphthylisoquinoline (NIQ) alkaloids and their synthetic analogues as multistage active antimalarial drug candidates. A total of 30 compounds were tested, of which 17 exhibited IC50 values <1 μM against drug-sensitive P. falciparum parasites (NF54 strain); 15 of these retained activity against a panel of drug-resistant strains.
A novel series of synthetic functionalized arylvinyl‐1,2,4‐trioxanes (8 a –p ) has been prepared and assessed for their in vitro antiplasmodial activity against the chloroquine‐resistant Pf INDO strain of Plasmodium falciparum by using a SYBR green‐I fluorescence assay. Compounds 8 g (IC50=0.051 μM; SI=589.41) and 8 m (IC50=0.059 μM; SI=55.93) showed 11‐fold and >9‐fold more potent antiplasmodial activity, respectively, as compared to chloroquine (IC50=0.546 μM; SI=36.63).
Malaria greatly affects the world health, having caused more than 228 million cases only in 2018. The emergence of drug resistance is one of the main problems in its treatment, demonstrating the urge for the development of new antimalarial drugs.
A novel series of functionalized synthetic substituted arylvinyl‐1,2,4‐trioxanes ( 8a‐p ) has been prepared and assessed for in vitro antiplasmodial activity against chloroquine‐resistant Pf INDO strain of Plasmodium falciparum using SYBR green‐I fluorescence assay. Compounds 8g (IC 50 = 0.051 µ M; SI = 589.41) and 8m (IC 50 = 0.059 µ M; SI = 55.93) showed 11‐fold and > 9‐fold more potent antiplasmodial activity, respectively as compared to chloroquine (IC 50 = 0.546 µ M; SI = 36.63).
Conjugation of organometallic complexes to known bioactive organic frameworks is a proven strategy revered for devising new drug molecules with novel modes of action. Herein, we present the in vitro antimalarial and antiproliferative investigation of ferrocenyl α‐aminocresol conjugates assembled by amalgamation of the organometallic ferrocene unit and the α‐aminocresol scaffold.