Synergistic blending of high-valued heterocycles inhibits growth of Plasmodium falciparum in culture and P. berghei infection in mouse model

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 sho...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Prashant Kumar, Angela O. Achieng, Vinoth Rajendran, Prahlad C. Ghosh, Brajendra K. Singh, Manmeet Rawat, Douglas J. Perkins, Prakasha Kempaiah, Brijesh Rathi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c1c71899bdf946b8987fa7373bc03d37
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c1c71899bdf946b8987fa7373bc03d37
record_format	dspace
spelling	oai:doaj.org-article:c1c71899bdf946b8987fa7373bc03d372021-12-02T15:06:10ZSynergistic blending of high-valued heterocycles inhibits growth of Plasmodium falciparum in culture and P. berghei infection in mouse model10.1038/s41598-017-06097-z2045-2322https://doaj.org/article/c1c71899bdf946b8987fa7373bc03d372017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06097-zhttps://doaj.org/toc/2045-2322Abstract 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.Prashant KumarAngela O. AchiengVinoth RajendranPrahlad C. GhoshBrajendra K. SinghManmeet RawatDouglas J. PerkinsPrakasha KempaiahBrijesh RathiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Prashant Kumar Angela O. Achieng Vinoth Rajendran Prahlad C. Ghosh Brajendra K. Singh Manmeet Rawat Douglas J. Perkins Prakasha Kempaiah Brijesh Rathi Synergistic blending of high-valued heterocycles inhibits growth of Plasmodium falciparum in culture and P. berghei infection in mouse model
description	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.
format	article
author	Prashant Kumar Angela O. Achieng Vinoth Rajendran Prahlad C. Ghosh Brajendra K. Singh Manmeet Rawat Douglas J. Perkins Prakasha Kempaiah Brijesh Rathi
author_facet	Prashant Kumar Angela O. Achieng Vinoth Rajendran Prahlad C. Ghosh Brajendra K. Singh Manmeet Rawat Douglas J. Perkins Prakasha Kempaiah Brijesh Rathi
author_sort	Prashant Kumar
title	Synergistic blending of high-valued heterocycles inhibits growth of Plasmodium falciparum in culture and P. berghei infection in mouse model
title_short	Synergistic blending of high-valued heterocycles inhibits growth of Plasmodium falciparum in culture and P. berghei infection in mouse model
title_full	Synergistic blending of high-valued heterocycles inhibits growth of Plasmodium falciparum in culture and P. berghei infection in mouse model
title_fullStr	Synergistic blending of high-valued heterocycles inhibits growth of Plasmodium falciparum in culture and P. berghei infection in mouse model
title_full_unstemmed	Synergistic blending of high-valued heterocycles inhibits growth of Plasmodium falciparum in culture and P. berghei infection in mouse model
title_sort	synergistic blending of high-valued heterocycles inhibits growth of plasmodium falciparum in culture and p. berghei infection in mouse model
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c1c71899bdf946b8987fa7373bc03d37
work_keys_str_mv	AT prashantkumar synergisticblendingofhighvaluedheterocyclesinhibitsgrowthofplasmodiumfalciparumincultureandpbergheiinfectioninmousemodel AT angelaoachieng synergisticblendingofhighvaluedheterocyclesinhibitsgrowthofplasmodiumfalciparumincultureandpbergheiinfectioninmousemodel AT vinothrajendran synergisticblendingofhighvaluedheterocyclesinhibitsgrowthofplasmodiumfalciparumincultureandpbergheiinfectioninmousemodel AT prahladcghosh synergisticblendingofhighvaluedheterocyclesinhibitsgrowthofplasmodiumfalciparumincultureandpbergheiinfectioninmousemodel AT brajendraksingh synergisticblendingofhighvaluedheterocyclesinhibitsgrowthofplasmodiumfalciparumincultureandpbergheiinfectioninmousemodel AT manmeetrawat synergisticblendingofhighvaluedheterocyclesinhibitsgrowthofplasmodiumfalciparumincultureandpbergheiinfectioninmousemodel AT douglasjperkins synergisticblendingofhighvaluedheterocyclesinhibitsgrowthofplasmodiumfalciparumincultureandpbergheiinfectioninmousemodel AT prakashakempaiah synergisticblendingofhighvaluedheterocyclesinhibitsgrowthofplasmodiumfalciparumincultureandpbergheiinfectioninmousemodel AT brijeshrathi synergisticblendingofhighvaluedheterocyclesinhibitsgrowthofplasmodiumfalciparumincultureandpbergheiinfectioninmousemodel
_version_	1718388607959433216

Synergistic blending of high-valued heterocycles inhibits growth of Plasmodium falciparum in culture and P. berghei infection in mouse model

Ejemplares similares