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Medicinal Chemistry Research

, Volume 25, Issue 6, pp 1148–1162 | Cite as

Design, synthesis, and in vitro antiplasmodial activity of 4-aminoquinolines containing modified amino acid conjugates

  • Kondaparla Srinivasarao
  • Pooja Agarwal
  • Kumkum Srivastava
  • W. Haq
  • Sunil K. Puri
  • S. B. Katti
Original Research

Abstract

A new series of side chain-modified 4-aminoquinolines were synthesized and screened for in vitro antiplasmodial activity against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. Among the series, compounds 30 and 31 showed significant inhibition of parasite growth against K1 strain of P. falciparum with IC50 values 0.28 and 0.31 µM, respectively, whereas compounds 34, 35, and 38 exhibited superior activity against K1 strain with IC50 values 0.18, 0.22, and 0.17 µM, respectively, as compared to 0.255 µM for chloroquine (CQ). All the compounds displayed good resistance factor between 1.54 and >34.48 as against 51.0 for CQ. All these analogues were found to form strong complex with hematin and inhibited the β-hematin formation in vitro, suggesting that this class of compounds act on a heme polymerization target. Overall results suggest that present series of compounds appear to be promising for further lead optimization to obtain compounds active against drug-resistant parasites.

Graphical Abstract

Keywords

Antiplasmodial activity Heme binding Chloroquine Plasmodium falciparum β-Hematin Chloroquine-sensitive strain Chloroquine-resistant strain 

Abbreviations

CQ

Chloroquine

DCC

N,N′-dicyclohexylcarbodiimide

HOBt

Hydroxybenzotriazole

DMF

Dimethylformamide

DMSO

Dimethyl sulfoxide

Notes

Acknowledgments

One of the authors (K.S.R) thanks the CSIR, New Delhi, for Senior Research Fellowship. Authors thank the Director, CDRI, for the support, and the SAIF division for the spectral data. The CDRI Communication No is 9197.

Compliance with ethical standards

Conflicts of interest

The authors have no conflict of interest to declare.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Kondaparla Srinivasarao
    • 1
  • Pooja Agarwal
    • 2
  • Kumkum Srivastava
    • 2
  • W. Haq
    • 1
  • Sunil K. Puri
    • 2
  • S. B. Katti
    • 1
  1. 1.Medicinal and Process Chemistry DivisionCSIR-Central Drug Research InstituteLucknowIndia
  2. 2.Parasitology DivisionCSIR-Central Drug Research InstituteLucknowIndia

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