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Medicinal Chemistry Research

, Volume 27, Issue 5, pp 1345–1354 | Cite as

Antimalarial activity of phytol derivatives: in vitro and in vivo study

  • Archana Saxena
  • Harish C. Upadhyay
  • Harveer S. Cheema
  • Santosh K. Srivastava
  • Mahendra P. Darokar
  • Dnyaneshwar U. Bawankule
Original Research

Abstract

Severe malaria is one of the leading causes of mortality among children and pregnant woman globally. Resistance development against the frontline antimalarial drugs has created an alarming situation, which requires intensive drug discovery to develop effective, affordable, and accessible antimalarial agents possessing novel modes of action. As a part of our drug discovery program for antimalarial agents from plants, phytol a very commonly occurring diterpene alcohol in the plant was investigated for its antimalarial potential. In vitro antiplasmodial activity against the chloroquine-sensitive Plasmodium falciparum NF54 by measuring the parasite specific lactate dehydrogenase (pfLDH), showed moderate activity (IC50 211.5 ± 0.93 µM). Further, phytol was chemically converted into thirteen derivatives, which were evaluated for their antiplasmodial potential. All the derivatives were moderate active, but among all the derivatives palmitoyl (PhY-3; IC50 12.13 ± 0.31 µM) has found most active without any cytotoxic effect on macrophage cells. PhY-3 was further validated in an in vivo system for its efficacy and safety profile in mice. Oral administration of PhY-3 showed significant reduction of parasitemia and increased mean survival time. It also attributed significant increase in blood glucose and hemoglobin level, when compared with vehicle-treated P. berghei infected mice without any toxic effect on normal mice at a higher dose. These findings confirm suitability of the phytol derivatives as new chemical entities for further investigation towards the management of malaria.

Keywords

Phytol In vitro In vivo Plasmodium Malaria Mice 

Notes

Acknowledgements

We acknowledge the Council of Scientific and Industrial Research (CSIR), New Delhi, India for financial support through XII FYP networking projects BSC-0203. We are thankful to Director, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India for rendering essential research facilities and support. ICMR-Senior Research Fellowship to Ms. Archana Saxena is duly acknowledged.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2017_2132_MOESM1_ESM.ppt (128 kb)
Supplementary Figure
44_2017_2132_MOESM2_ESM.docx (454 kb)
Supplementary Table

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Archana Saxena
    • 1
  • Harish C. Upadhyay
    • 2
    • 4
  • Harveer S. Cheema
    • 1
    • 3
  • Santosh K. Srivastava
    • 2
    • 3
  • Mahendra P. Darokar
    • 1
    • 3
  • Dnyaneshwar U. Bawankule
    • 1
    • 3
  1. 1.Molecular Bioprospection DepartmentCSIR-Central Institute of Medicinal and Aromatic PlantsLucknowIndia
  2. 2.Medicinal Chemistry DepartmentCSIR-Central Institute of Medicinal and Aromatic PlantsLucknowIndia
  3. 3.Academy of Scientific and Innovative Research (AcSIR), Anusandhan BhawanNew DelhiIndia
  4. 4.Applied Science DepartmentRajkiya Engineering CollegeSonbhadra, UPIndia

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