TY - JOUR
T1 - Identification of Compounds with Efficacy against Malaria Parasites from Common North American Plants
AU - Cai, Shengxin
AU - Risinger, April L.
AU - Nair, Shalini
AU - Peng, Jiangnan
AU - Anderson, Timothy J.C.
AU - Du, Lin
AU - Powell, Douglas R.
AU - Mooberry, Susan L.
AU - Cichewicz, Robert H.
N1 - Funding Information:
Support for this project was provided by a pilot studies grant from the Texas Biomedical Forum and R21AI092235 awarded to S.L.M. and T.J.C.A. from the National Institute for Allergy and Infectious Disease, National Institutes of Health (NIH), Bethesda, MD. This investigation was conducted in facilities constructed with support from Research Facilities Improvement Program grants C06 RR013556 and RR017515 from the National Center for Research Resources of the NIH. Parasite clone NHP1337 was isolated from an infected blood sample collected on the Thailand-Myanmar border provided by F. Nosten. T.J.C.A. and S.N. are supported by grant R37AI048071 from the National Institute of Allergy and Infectious Diseases. The LC-MS instrument used for this project was provided in part by a Challenge Grant from the Office of the Vice President for Research, University of Oklahoma, Norman Campus, and an award through the Shimadzu Equipment Grant Program (R.H.C.). We thank A. Robles and L. Clark for their assistance in plant collections and extractions and the San Antonio Botanical Garden for access to plant samples.
PY - 2016/3/25
Y1 - 2016/3/25
N2 - Some of the most valuable antimalarial compounds, including quinine and artemisinin, originated from plants. While these drugs have served important roles over many years for the treatment of malaria, drug resistance has become a widespread problem. Therefore, a critical need exists to identify new compounds that have efficacy against drug-resistant malaria strains. In the current study, extracts prepared from plants readily obtained from local sources were screened for activity against Plasmodium falciparum. Bioassay-guided fractionation was used to identify 18 compounds from five plant species. These compounds included eight lupane triterpenes (1-8), four kaempferol 3-O-rhamnosides (10-13), four kaempferol 3-O-glucosides (14-17), and the known compounds amentoflavone and knipholone. These compounds were tested for their efficacy against multi-drug-resistant malaria parasites and counterscreened against HeLa cells to measure their antimalarial selectivity. Most notably, one of the new lupane triterpenes (3) isolated from the supercritical extract of Buxus sempervirens, the common boxwood, showed activity against both drug-sensitive and -resistant malaria strains at a concentration that was 75-fold more selective for the drug-resistant malaria parasites as compared to HeLa cells. This study demonstrates that new antimalarial compounds with efficacy against drug-resistant strains can be identified from native and introduced plant species in the United States, which traditionally have received scant investigation compared to more heavily explored tropical and semitropical botanical resources from around the world.
AB - Some of the most valuable antimalarial compounds, including quinine and artemisinin, originated from plants. While these drugs have served important roles over many years for the treatment of malaria, drug resistance has become a widespread problem. Therefore, a critical need exists to identify new compounds that have efficacy against drug-resistant malaria strains. In the current study, extracts prepared from plants readily obtained from local sources were screened for activity against Plasmodium falciparum. Bioassay-guided fractionation was used to identify 18 compounds from five plant species. These compounds included eight lupane triterpenes (1-8), four kaempferol 3-O-rhamnosides (10-13), four kaempferol 3-O-glucosides (14-17), and the known compounds amentoflavone and knipholone. These compounds were tested for their efficacy against multi-drug-resistant malaria parasites and counterscreened against HeLa cells to measure their antimalarial selectivity. Most notably, one of the new lupane triterpenes (3) isolated from the supercritical extract of Buxus sempervirens, the common boxwood, showed activity against both drug-sensitive and -resistant malaria strains at a concentration that was 75-fold more selective for the drug-resistant malaria parasites as compared to HeLa cells. This study demonstrates that new antimalarial compounds with efficacy against drug-resistant strains can be identified from native and introduced plant species in the United States, which traditionally have received scant investigation compared to more heavily explored tropical and semitropical botanical resources from around the world.
UR - http://www.scopus.com/inward/record.url?scp=84962338897&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962338897&partnerID=8YFLogxK
U2 - 10.1021/acs.jnatprod.5b00874
DO - 10.1021/acs.jnatprod.5b00874
M3 - Article
C2 - 26722868
AN - SCOPUS:84962338897
VL - 79
SP - 490
EP - 498
JO - Journal of Natural Products
JF - Journal of Natural Products
SN - 0163-3864
IS - 3
ER -