TY - JOUR
T1 - Borrelidin analogues with antimalarial activity
T2 - Design, synthesis and biological evaluation against Plasmodium falciparum parasites
AU - Sugawara, Akihiro
AU - Tanaka, Toshiaki
AU - Hirose, Tomoyasu
AU - Ishiyama, Aki
AU - Iwatsuki, Masato
AU - Takahashi, Yoko
AU - Otoguro, Kazuhiko
AU - Omura, Satoshi
AU - Sunazuka, Toshiaki
N1 - Funding Information:
This work was supported by a Grant for the 21st Century COE Program, together with funds from the Quality Assurance Framework of Higher Education from The Ministry of Education, Culture, Sports, Science and Technology (MEXT) , Japan and a Grant for All Kitasato Project Study (AKPS). We thank Ms. Hitomi Sekiguchi and Ms. Miyuki Namatame (Kitasato University) for their technical assistance. We also thank Ms. Chikako Sakabe, Ms. Akiko Nakagawa and Ms. Noriko Sato (Kitasato University) for various instrumental analyses.
PY - 2013/4/15
Y1 - 2013/4/15
N2 - Borrelidin, a structurally unique 18-membered macrolide, was found to express antimalarial activity against drug-resistant Plasmodium falciparum malaria parasites, with IC50 value of 0.93 ng/mL. However, it also displays strong cytotoxicity against human diploid embryonic MRC-5 cells. To investigate the issue of the cytotoxicity of borrelidin, borrelidin-based analogues were synthesized and their anti-Plasmodium properties were evaluated. In this communication, we report that a novel borrelidin analogue, bearing the CH2SPh moiety via a triazole linkage, was found to retain a potent antimalarial activity, against drug-sensitive and drug-resistant parasite strains, but possess only weak cytotoxicity against human cells.
AB - Borrelidin, a structurally unique 18-membered macrolide, was found to express antimalarial activity against drug-resistant Plasmodium falciparum malaria parasites, with IC50 value of 0.93 ng/mL. However, it also displays strong cytotoxicity against human diploid embryonic MRC-5 cells. To investigate the issue of the cytotoxicity of borrelidin, borrelidin-based analogues were synthesized and their anti-Plasmodium properties were evaluated. In this communication, we report that a novel borrelidin analogue, bearing the CH2SPh moiety via a triazole linkage, was found to retain a potent antimalarial activity, against drug-sensitive and drug-resistant parasite strains, but possess only weak cytotoxicity against human cells.
KW - Antimalarial
KW - Borrelidin
KW - Malaria
KW - Plasmodium falciparum
KW - Structure-activity relationships
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U2 - 10.1016/j.bmcl.2013.02.075
DO - 10.1016/j.bmcl.2013.02.075
M3 - Article
C2 - 23499502
AN - SCOPUS:84875423790
SN - 0960-894X
VL - 23
SP - 2302
EP - 2305
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 8
ER -
