2. Academic Validation
  3. Identification of β-Amino alcohol grafted 1,4,5 trisubstituted 1,2,3-triazoles as potent antimalarial agents

Identification of β-Amino alcohol grafted 1,4,5 trisubstituted 1,2,3-triazoles as potent antimalarial agents

  • Eur J Med Chem. 2016 Feb 15:109:187-98. doi: 10.1016/j.ejmech.2015.12.038.
Nalmala Devender 1,  Sarika Gunjan 2,  Stuti Chhabra 3,  Kartikey Singh 1,  Venkata Reddy Pasam 1,  Sanjeev K Shukla 4,  Abhisheak Sharma 5,  Swati Jaiswal 5,  Sunil Kumar Singh 6,  Yogesh Kumar 3,  Jawahar Lal 5,  Arun Kumar Trivedi 3,  Renu Tripathi 7,  Rama Pati Tripathi 8
Affiliations

Affiliations

  • 1 Medicinal and Process Chemistry Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
  • 2 Parasitology Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi 110001, India.
  • 3 Biochemistry Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
  • 4 Sophisticated Analytical Instrument Facility Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India. Electronic address: skshukla@cdri.res.in.
  • 5 Pharmacokinetics & Metabolism Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
  • 6 Parasitology Division, CSIR- Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.
  • 7 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.
  • 8 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.
PMID: 26774925 DOI: 10.1016/j.ejmech.2015.12.038
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.

Keywords

Antimalarial; Antiplasmodial; Pharmacokinetics; p53 protein upregulation; β-aminoalcohol.

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