Design, Synthesis, and Biological Evaluation of Novel 1, 2, 4‐Trioxanes as Potential Antimalarial Agents. Issue 3 (16th February 2017)

• Record Type: Journal Article
• Authors: Gupta, Amit K.; Varshney, Kanika; Kumar, Vivek; Srivastava, Kumkum; Pant, Aditya B.; Puri, Sunil K.; Saxena, Anil K.
• Is Part Of: Archiv der Pharmazie. Volume 350:Issue 3/4(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-02-16
• Subjects: 1, 2, 4‐Trioxanes -- Antimalarial -- Drug design -- Synthesis; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201600335
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract : 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 (compound15, IC50 = 25.71 nM; compound21, IC50 = 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. Compound21 may serve as an optimized lead compound because of its less in vitro toxicity and lower probability to cross the blood brain barrier. Abstract : A series of substituted 1, 2, 4‐trioxanes were synthesized and evaluated for their antimalarial potential, ADME properties, and neuronal cell cytotoxicity. Two compounds (15, IC50 = 25.71 nM;21, IC50 = 19.6 nM) showed in vitro antimalarial potential comparable to those of chloroquine and artemisinin. Due to its less toxicity and low probability to cross the blood brain barrier, compound21 can be considered an optimized lead.