title: Design, Synthesis, and Biological Evaluation of Novel 1,2,4-Trioxanes as Potential Antimalarial Agents.
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 (compound 15, IC50= 25.71 nM; compound 21, 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. 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.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Gupta
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Kanika
authors.initials: K
authors.lastname: Varshney
authors.affiliation: In Vitro Toxicology Laboratory, CSIR-Indian Institute of Toxicology Research, Lucknow, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Kumkum
authors.initials: K
authors.lastname: Srivastava
authors.affiliation: In Vitro Toxicology Laboratory, CSIR-Indian Institute of Toxicology Research, Lucknow, India.
authors.forename: Aditya B
authors.initials: AB
authors.lastname: Pant
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Puri
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Saxena
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: C503429:1,2,4-trioxane; D000962:Antimalarials; D006571:Heterocyclic Compounds
keywords: 1,2,4-Trioxanes; Antimalarial; Drug design; Synthesis