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Medicinal Chemistry Research

, Volume 26, Issue 10, pp 2499–2513 | Cite as

Isolation of isoxanthanol and synthesis of novel derivatives as potential cytotoxic agents

  • Praveen K. Chinthakindi
  • Santosh K. Rath
  • Jasvinder Singh
  • Shashank Singh
  • Surrinder Koul
  • Payare L. Sangwan
Original Research
  • 180 Downloads

Abstract

Novel synthetic derivatives of sesquiterpene lactone isoxanthanol (1) have been prepared and bioevaluated against four human cancer cell lines viz. T98G (glioblastoma), A431 (epidermoid carcinoma), NCI-H322 (bronchioloalveolar carcinoma), and A549 (lung adeno carcinoma) for their cytotoxic potential using paclitaxel as the standard. This has resulted in the identification of potent molecules displaying IC50 1.9 and 5.0 µM, respectively against the A549 cancer cell line. The study has resulted in the identification of potential cytotoxic activity of the analog (compound 10) bearing electron donating aryl alkenoic substituent. Furthermore, the induction of cell death has been assessed for the most active compound (10) using flow cytometric method and sub-G1 cell population determination by propidium iodide staining. The concentration dependent inhibitory effect of 10 on the A549 cells ability did not reproduce and form colonies at 20 µM concentration.

Graphical Abstract

Synthesis of isoxanthanol derivatives and their cytotoxic study resulted in identification of potential cytotoxic agents. Compound 10, one of its aryl alkenoic substituent showed potency against NCI-H322 (bronchioloalveolar carcinoma), and A549 (lung adeno carcinoma) cell lines.

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Keywords

Isoxanthanol Sesquiterpene Lactone Human leukemia 

Abbreviations

NP’s

Natural products

SLs

Sesquiterpene lactones

NCEs

New chemical entities

FDA

Food and drugs administration

J

Coupling constant

HRMS

High resolution mass spectra

PBS

Phosphate buffer saline

SRB

Sulforhodamine B

TCA

Trichloroacetic acid

DMAP

N,N-dimethyl amino pyridine

CC

Column chromatography

Notes

Acknowledgements

The CSIR is well acknowledged for financial support under 12th five-year project BSC0108. The authors thank Botany division of the Institute for providing the plant material, Instrumentation division for spectral data, and CSIR-UGC for the award of Fellowship to one of the author (PKC). IIIM publication no. IIIM/2011/2017.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_1949_MOESM1_ESM.docx (12 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Praveen K. Chinthakindi
    • 1
  • Santosh K. Rath
    • 1
    • 2
  • Jasvinder Singh
    • 2
    • 3
  • Shashank Singh
    • 2
    • 3
  • Surrinder Koul
    • 1
  • Payare L. Sangwan
    • 1
    • 2
  1. 1.Bioorganic Chemistry DivisionCSIR-Indian Institute of Integrative MedicineJammuIndia
  2. 2.Academy of Scientific and Innovative Research (AcSIR), CSIR-IIIM CampusJammuIndia
  3. 3.Cancer Pharmacology DivisionCSIR-Indian Institute of Integrative MedicineJammuIndia

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