https://orcid.org/0000-0003-2421-1382
Abstract
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.
Graphical abstract
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at:www.futurescience/doi/suppl/10.4155/fmc-2019-0260
Financial & competing interests disclosure
A Rani thanks CSIR, New Delhi, India, for providing financial assistance under CSIR-SRF Fellowship [09/254(0269)/2017-EMR-I]. V Kumar acknowledges the Science and Engineering Research Board (SERB), New Delhi, for providing financial support [EMR/2015/001687]. We would also like to thank the Centre for High-Performance Computing based in Cape Town for access to computational resources. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.