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Design, Synthesis, and Biological Evaluation of Novel 1,2,4‐Trioxanes as Potential Antimalarial Agents
Author(s) -
Gupta Amit K.,
Varshney Kanika,
Kumar Vivek,
Srivastava Kumkum,
Pant Aditya B.,
Puri Sunil K.,
Saxena Anil K.
Publication year - 2017
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201600335
Subject(s) - artemisinin , adme , chemistry , in silico , cytotoxicity , in vitro , ic50 , chloroquine , lead compound , combinatorial chemistry , stereochemistry , antimalarial agent , toxicity , pharmacology , plasmodium falciparum , biochemistry , organic chemistry , biology , malaria , gene , immunology
A series of substituted 1,2,4‐trioxanes were synthesized and evaluated for their antimalarial potential, in silico ADME properties and cytotoxicity on neuronal cell lines. Among the 15 synthesized substituted 1,2,4‐trioxanes, two compounds (compound 15 , IC 50 = 25.71 nM; compound 21 , IC 50 = 19.6 nM) exhibited promising in vitro antimalarial potential comparable to those of the existing drugs chloroquine and artemisinin. Both of these compounds were found to be nontoxic up to 20 µM concentration in neuronal PC‐12 cells. Compound 21 may serve as an optimized lead compound because of its less in vitro toxicity and lower probability to cross the blood brain barrier.