Synergistic blending of high-valued heterocycles inhibits growth of Plasmodium falciparum in culture and P. berghei infection in mouse model
Authors: Douglas J Perkins
Brajendra K Singh
Prahlad C Ghosh
Vinoth Rajendran
Brijesh Rathi
Manmeet Rawat
Angela O Achieng
Prakasha Kempaiah
Prashant Kumar
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: phthalimide analogues; growth inhibitors; Plasmodium falciparum; click-chemistry; microwave heating
Affiliations: Bio-Organic Research Laboratory, Department of Chemistry, University of Delhi, Delhi, 110007, India., Department of Internal Medicine, Center for Global Health, University of New Mexico Health Sciences Center, Albuquerque, NM, United States of America., Department of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, Kenya., Department of Biochemistry, University of Delhi South Campus, New Delhi, 110021, India., Department of Internal Medicine, Center for Global Health, University of New Mexico Health Sciences Center, Albuquerque, NM, United States of America. ., Department of Chemistry, Hansraj College University Enclave, University of Delhi, Delhi, 110007, India. ., Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA-02139, United States of America. .

Abstract:  A series of phthalimide analogues, novelized with high-valued bioactive scaffolds was synthesized by means of click-chemistry under non-conventional microwave heating and evaluated as noteworthy growth inhibitors of Plasmodium falciparum (3D7 and W2) in culture. Analogues 6a, 6h and 6 u showed highest activity to inhibit the growth of the parasite with IC50 values in submicromolar range. Structure-activity correlation indicated the necessity of unsubstituted triazoles and leucine linker to obtain maximal growth inhibition of the parasite. Notably, phthalimide 6a and 6u selectively inhibited the ring-stage growth and parasite maturation. On other hand, phthalimide 6h displayed selective schizonticidal activity. Besides, they displayed synergistic interactions with chloroquine and dihydroartemisinin against parasite. Additional in vivo experiments using P. berghei infected mice showed that administration of 6h and 6u alone, as well as in combination with dihydroartemisinin, substantially reduced the parasite load. The high antimalarial activity of 6h and 6u, coupled with low toxicity advocate their potential role as novel antimalarial agents, either as standalone or combination therapies. 

Retracted: No

PubPeer comments:
 Figure 3E appears to include 2 overlapping images, cropped differently and with slightly different dimensions. Marked in orange and green. Similar to issues with paper with shared authors posted here: https: pubpeer.com publications 844DD76D90A960672975C6C5E3127D *** ![file] , 
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 #2 Dr. Kempaiah, thank you for your reply. Will you be contacting the journal with this correction? Also, I note that in your corrected figure, the control images for 0h and 6h have swapped positions. Was this intentional? , 
 This was not intentional, these are verified now and accurate representations... Thank you for the comments and helping We would be contacting the Journal to replace the old images. ,