31 research outputs found
Antimalarial Activity and Mechanisms of Action of Two Novel 4-Aminoquinolines against Chloroquine-Resistant Parasites
Chloroquine (CQ) is a cost effective antimalarial drug with a relatively good safety profile (or therapeutic index). However, CQ is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of CQ-resistant strains, also reported for P. vivax. Despite CQ resistance, novel drug candidates based on the structure of CQ continue to be considered, as in the present work. One CQ analog was synthesized as monoquinoline (MAQ) and compared with a previously synthesized bisquinoline (BAQ), both tested against P. falciparum in vitro and against P. berghei in mice, then evaluated in vitro for their cytotoxicity and ability to inhibit hemozoin formation. Their interactions with residues present in the NADH binding site of P falciparum lactate dehydrogenase were evaluated using docking analysis software. Both compounds were active in the nanomolar range evaluated through the HRPII and hypoxanthine tests. MAQ and BAQ derivatives were not toxic, and both compounds significantly inhibited hemozoin formation, in a dose-dependent manner. MAQ had a higher selectivity index than BAQ and both compounds were weak PfLDH inhibitors, a result previously reported also for CQ. Taken together, the two CQ analogues represent promising molecules which seem to act in a crucial point for the parasite, inhibiting hemozoin formation
Direct Amidation of Aldoses and Decarboxylative Amidation of α-Keto Acids: An Efficient Conjugation Method for Unprotected Carbohydrate Molecules
Palladium complex immobilized on graphene oxide–magnetic nanoparticle composites for ester synthesis by aerobic oxidative esterification of alcohols
Reversal Agent and Linker Variants of Reversed Chloroquines: Activities against Plasmodium falciparum
Antiplasmodial activity, in vivo pharmacokinetics and anti-malarial efficacy evaluation of hydroxypyridinone hybrids in a mouse model
Design, synthesis, and in vitro antiplasmodial activity of 4-aminoquinolines containing modified amino acid conjugates
N-heterocyclic carbene-mediated oxidative electrosynthesis of esters in a microflow cell
An efficient N-heterocyclic carbene (NHC)-mediated oxidative esterification of aldehydes has been achieved in an undivided microfluidic electrolysis cell at ambient temperature. Productivities of up to 4.3 g h?1 in a single pass are demonstrated, with excellent yields and conversions for 19 examples presented. Notably, the oxidative acylation reactions were shown to proceed with a 1:1 stoichiometry of aldehyde and alcohol (for primary alcohols), with remarkably short residence times in the electrolysis cell (<13 s), and without added electrolyte