2. Academic Validation
  3. Synthesis of isatin based N1-alkylated 3-β-C-glycoconjugated-oxopropylidene oxindoles as potent antiplasmodial agents

Synthesis of isatin based N1-alkylated 3-β-C-glycoconjugated-oxopropylidene oxindoles as potent antiplasmodial agents

  • Eur J Med Chem. 2019 Jan 15:162:448-454. doi: 10.1016/j.ejmech.2018.11.008.
Ravi Kumar Thakur 1,  Prince Joshi 2,  Kapil Upadhyaya 1,  Kartikey Singh 1,  Gaurav Sharma 3,  Sanjeev K Shukla 3,  Renu Tripathi 4,  Rama Pati Tripathi 5
Affiliations

Affiliations

  • 1 Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India.
  • 2 Parasitology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India.
  • 3 Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India; Sophisticated Analytical Instrument Facility, CSIR-Central Drug Research Institute, Lucknow, 226031, India.
  • 4 Parasitology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India. Electronic address: renu1113@rediffmail.com.
  • 5 Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India. Electronic address: rpt.cdri@gmail.com.
PMID: 30469040 DOI: 10.1016/j.ejmech.2018.11.008
Abstract

In an attempt to develop new antimalarial drugs, we have synthesized a new class of N-alkylated 3-glycoconjugated-oxopropylidene oxindoles starting from substituted isatins and glucopyranosyl propanone via a well-known cross-aldol reaction followed by dehydration. The newly synthesized compounds were screened for their in vitro antiplasmodial activity, and among all the compounds 9g, 9f, 9b, 8d, 9d, 9c, and 9e displayed potent activity with the IC50 values in the range of 0.1-0.3 μM against Chloroquine (CQ) sensitive Pf3D7 strain, while compounds 9d, 9b, 9e, 8c, 8f, 9c, and 9a have shown promising activity having IC50 values in 0.1-0.4 μM range against CQ resistant PfK1 strain, which is even better than the standard drug chloroquine with IC50 value of 0.5 μM.

Keywords

Antiplasmodial activity; Cross aldol reaction; Glucopyranosyl propanone; Isatin.

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