TY - JOUR
T1 - Bioisosteric transformations and permutations in the triazolopyrimidine scaffold to identify the minimum pharmacophore required for inhibitory activity against Plasmodium falciparum dihydroorotate dehydrogenase
AU - Marwaha, Alka
AU - White, John
AU - El Mazouni, Farah
AU - Creason, Sharon
AU - Kokkonda, Sreekanth
AU - Buckner, Frederick S
AU - Charman, Susan Ann
AU - Phillips, Margaret
AU - Rathod, Pradip
PY - 2012
Y1 - 2012
N2 - Malaria is a persistent and successful global disease that
threatens half of the world s population and kills up to a million
people each year. The developing world has urgently needed
new, safe, effective, and affordable antimalarial drugs since the
demise of chloroquine due to the emergence of resistant P.
falciparum strains. Strides have been made to develop an
array of antimalarial agents with artemisinin-based combination
therapies (ACTs) providing a major breakthrough, succeeding
in more than 90 of the malaria cases. However, artemisinin
effectiveness appears to be decreasing along the Thai-
Combodia border, threatening these recent gains. The
limitations of current antimalarial chemotherapy underscore the
need for novel drugs, ideally directed against innovative
therapeutic targets. The completion of the malaria genome
project has opened up channels to search for new targets in
the parasite. Despite the identification of many essential genes
and extensive efforts to understand the biology of the parasite,
very few unique validated targets have been identified. Hence,
the contemporary challenge is to blend our knowledge of
malaria genomics and drug discovery.
AB - Malaria is a persistent and successful global disease that
threatens half of the world s population and kills up to a million
people each year. The developing world has urgently needed
new, safe, effective, and affordable antimalarial drugs since the
demise of chloroquine due to the emergence of resistant P.
falciparum strains. Strides have been made to develop an
array of antimalarial agents with artemisinin-based combination
therapies (ACTs) providing a major breakthrough, succeeding
in more than 90 of the malaria cases. However, artemisinin
effectiveness appears to be decreasing along the Thai-
Combodia border, threatening these recent gains. The
limitations of current antimalarial chemotherapy underscore the
need for novel drugs, ideally directed against innovative
therapeutic targets. The completion of the malaria genome
project has opened up channels to search for new targets in
the parasite. Despite the identification of many essential genes
and extensive efforts to understand the biology of the parasite,
very few unique validated targets have been identified. Hence,
the contemporary challenge is to blend our knowledge of
malaria genomics and drug discovery.
UR - http://pubs.acs.org/doi/abs/10.1021/jm300351w
U2 - 10.1021/jm300351w
DO - 10.1021/jm300351w
M3 - Article
SN - 0022-2623
VL - 55
SP - 7425
EP - 7436
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 17
ER -