2. Academic Validation
  3. Discovery of 2,3-dihydro-1 H-pyrrolo[3,4- b]quinolin-1-one derivatives as possible antileishmanial agents

Discovery of 2,3-dihydro-1 H-pyrrolo[3,4- b]quinolin-1-one derivatives as possible antileishmanial agents

  • RSC Med Chem. 2022 May 11;13(6):746-760. doi: 10.1039/d2md00078d.
Anuradha Seth 1 2,  Anirban Ghoshal 2 3,  Varun Dewaker 3,  Ankita Rani 1 2,  Sangh Priya Singh 2 3,  Mukul Dutta 1 2,  Shivani Katiyar 1,  Sandeep Kumar Singh 2 4,  Mamunur Rashid 4,  Muhammad Wahajuddin 2 4,  Susanta Kar 1 2,  Ajay Kumar Srivastava 2 3
Affiliations

Affiliations

  • 1 Molecular Microbiology and Immunology Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India susantakar@cdri.res.in.
  • 2 Academy of Scientific and Innovative Research (AcSIR) Ghaziabad-201002 Uttar Pradesh India.
  • 3 Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India ajayk.srivastava@cdri.res.in.
  • 4 Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute Lucknow-226031 Uttar Pradesh India.
PMID: 35814931 DOI: 10.1039/d2md00078d
Abstract

A series of uniquely functionalized 2,3,-dihydro-1H-pyyrolo[3,4-b]quinolin-1-one derivatives were synthesized in one to two steps by utilizing a post-Ugi modification strategy and were evaluated for antileishmanial efficacy against visceral leishmaniasis (VL). Among the library compounds, compound 5m exhibited potential in vitro antileishmanial activity (CC50 = 65.11 μM, SI = 7.79, anti-amastigote IC50 = 8.36 μM). In vivo antileishmanial evaluation of 5m demonstrated 56.2% inhibition in liver and 61.1% inhibition in spleen Parasite burden in infected Balb/c mice (12.5 mg kg-1, i.p.). In vitro pharmacokinetic study ascertained the stability of 5m in both simulated gastric fluid and simulated intestinal fluid. All the active compounds passed the PAINS filter and showed no toxicity in in silico predictions.

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