Pyrrolidine-Acridine hybrid in Artemisinin-based combination: A pharmacodynamic study

Swaroop Kumar Pandey, Subhasish Biswas, Sarika Gunjan, Bhavana Singh Chauhan, Sunil Kumar Singh, Kumkum Srivastava, Sarika Singh, Sanjay Batra, Renu Tripathi

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Aiming to develop new artemisinin-based combination therapy (ACT) for malaria, antimalarial effect of a new series of pyrrolidine-acridine hybrid in combination with artemisinin derivatives was investigated. Synthesis, antimalarial and cytotoxic evaluation of a series of hybrid of 2-(3-(substitutedbenzyl)pyrrolidin-1-yl)alkanamines and acridine were performed and mode of action of the lead compound was investigated. In vivo pharmacodynamic properties (parasite clearance time, parasite reduction ratio, dose and regimen determination) against multidrug resistant (MDR) rodent malaria parasite and toxicological parameters (median lethal dose, liver function test, kidney function test) were also investigated. 6-Chloro-N-(4-(3-(3,4-dimethoxybenzyl)pyrrolidin-1-yl)butyl)-2-methoxyacridin-9-amine (15c) has shown a dose dependent haem bio-mineralization inhibition and was found to be the most effective and safe compound against MDR malaria parasite in Swiss mice model. It displayed best antimalarial potential with artemether (AM) in vitro as well as in vivo. The combination also showed favourable pharmacodynamic properties and therapeutic response in mice with established MDR malaria infection and all mice were cured at the determined doses. The combination did not show toxicity at the doses administered to the Swiss mice. Taken together, our findings suggest that compound 15c is a potential partner with AM for the ACT and could be explored for further development.

Original languageEnglish
Pages (from-to)1421-1432
Number of pages12
Issue number11
StatePublished - 1 Sep 2016
Externally publishedYes


  • ACT
  • Malaria
  • combination therapy
  • multidrug resistant
  • pharmacodynamics
  • pyrrolidine-acridine hybrid

ASJC Scopus subject areas

  • Parasitology
  • Animal Science and Zoology
  • Infectious Diseases


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