title: Identification of β-Amino alcohol grafted 1,4,5 trisubstituted 1,2,3-triazoles as potent antimalarial agents.
abstract: In a quest to discover new drugs, we have synthesized a series of novel β-amino alcohol grafted 1,2,3-triazoles and screened them for their in vitro antiplasmodial and in vivo antimalarial activity. Among them, compounds 16 and 25 showed potent activity against chloroquine-sensitive (Pf3D7) strain with IC50 of 0.87 and 0.3 μM respectively, while compounds 7 and 13 exhibited better activity in vitro than the reference drug against chloroquine-resistance strain (PfK1) with IC50 of 0.5 μM each. Compound 25 showed 86.8% in vivo antimalarial efficacy with favorable pharmacokinetic parameters. Mechanistic studies divulged that potent compounds significantly boosted p53 protein levels to exhibit the antimalarial activity.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
authors.forename: Nalmala
authors.initials: N
authors.lastname: Devender
authors.affiliation: Parasitology Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India.
authors.forename: Sarika
authors.initials: S
authors.lastname: Gunjan
authors.affiliation: Biochemistry Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
authors.forename: Stuti
authors.initials: S
authors.lastname: Chhabra
authors.affiliation: Medicinal and Process Chemistry Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
authors.forename: Kartikey
authors.initials: K
authors.lastname: Singh
authors.affiliation: Medicinal and Process Chemistry Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
authors.forename: Venkata Reddy
authors.initials: VR
authors.lastname: Pasam
authors.affiliation: Sophisticated Analytical Instrument Facility Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India. Electronic address: skshukla@cdri.res.in.
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Shukla
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
authors.forename: Abhisheak
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Jaiswal
authors.affiliation: Parasitology Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Biochemistry Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Kumar
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
authors.forename: Jawahar
authors.initials: J
authors.lastname: Lal
authors.affiliation: Biochemistry Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
authors.forename: Arun Kumar
authors.initials: AK
authors.lastname: Trivedi
authors.affiliation: Parasitology Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India. Electronic address: renu_tripathi@cdri.res.in.
authors.forename: Renu
authors.initials: R
authors.lastname: Tripathi
authors.affiliation: Medicinal and Process Chemistry Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India. Electronic address: rpt.cdri@gmail.com.
authors.forename: Rama Pati
authors.initials: RP
authors.lastname: Tripathi
mesh_terms: D000605:Amino Alcohols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002522:Chlorocebus aethiops; D006801:Humans; D061986:MCF-7 Cells; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D014709:Vero Cells
chemical_list: D000605:Amino Alcohols; D000962:Antimalarials; D014230:Triazoles; D016159:Tumor Suppressor Protein p53
keywords: Antimalarial; Antiplasmodial; Pharmacokinetics; p53 protein upregulation; β-aminoalcohol