Design, synthesis, heme binding and density functional theory studies of isoindoline-dione-4-aminoquinolines as potential antiplasmodials.
Aim: WHO Malaria report 2017 estimated 216 million cases of malaria and 445,000 deaths worldwide, with 91% of deaths affecting the African region. Results/methodology: Microwave promoted the synthesis of cycloalkyl amine substituted isoindoline-1,3-dione-4-aminoquinolines was urbanized for evaluating their antiplasmodial activities. Compound with the optimum combination of propyl chain length and hydroxyethyl piperazine proved to be the most potent among the synthesized scaffolds against chloroquine-resistant W2 strain of Plasmodium falciparum with an IC50 value of 0.006 μM. Heme-binding along with density functional theory studies were further carried out in order to delineate the mechanism of action of the most active compound. Conclusion: The synthesized scaffold can act as a therapeutic template for further synthetic modifications toward the search for a new antimalarial agent.
['Rani|Anu|A|', 'Kumar|Sumit|S|', 'Legac|Jenny|J|', 'Adeniyi|Adebayo A|AA|0000-0003-2421-1382', 'Awolade|Paul|P|', 'Singh|Parvesh|P|', 'Rosenthal|Philip J|PJ|', 'Kumar|Vipan|V|']
D000634:Aminoquinolines D000962:Antimalarials D001665:Binding Sites D000077318:Density Functional Theory D015195:Drug Design D006418:Heme D006801:Humans D054833:Isoindoles D008288:Malaria D008872:Microwaves D015394:Molecular Structure D021261:Parasitic Sensitivity Tests D010963:Plasmodium falciparum
density functional theory Antiplasmodial microwave Isoindoline-1,3-dione-4-aminoquinoline cycloalkyl-amine cytotoxicity heme-binding studies