Novel pyrrolobenzoxaboroles: design, synthesis, and biological evaluation against Trypanosoma brucei.
Human African trypanosomiasis is a fatal parasitic infection caused by the protozoan Trypanosoma brucei. The development of novel antitrypanosomal agents is urgently needed. Here we report the synthesis and structure-activity relationship of a new class of benzoxaboroles as antitrypanosomal agents. These compounds showed antiparasitic IC50 values ranging from 4.02 to 0.03 μg/mL and satisfactory cytotoxicity profile. Three of the lead compounds were demonstrated to cure the parasitic infection in a murine acute infection model. The structure-activity relationship of the pyrrolobenzoxaboroles are also discussed.
State Key Laboratory of Microbial Metabolism, and School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
Puhua
P
Wu
State Key Laboratory of Microbial Metabolism, and School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
Jiong
J
Zhang
State Key Laboratory of Microbial Metabolism, and School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
Qingqing
Q
Meng
Scynexis, Inc., P.O. Box 12878, Research Triangle Park, NC 27709-2878, United States.
Bakela
B
Nare
Scynexis, Inc., P.O. Box 12878, Research Triangle Park, NC 27709-2878, United States.
Robert T
RT
Jacobs
State Key Laboratory of Microbial Metabolism, and School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China. Electronic address: hczhou@sjtu.edu.cn.
Huchen
H
Zhou
D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000254:growth & development; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000662:veterinary
D001896:Boron Compounds; D011758:Pyrroles; D014344:Trypanocidal Agents
Antitrypanosomal agent; Human African trypanosomiasis; Indolobenzoxaboroles; Pyrrolobenzoxaboroles; Structure–activity relationship