2. Academic Validation
  3. Synthesis of a series of novel dihydroartemisinin monomers and dimers containing chalcone as a linker and their anticancer activity

Synthesis of a series of novel dihydroartemisinin monomers and dimers containing chalcone as a linker and their anticancer activity

  • Eur J Med Chem. 2016 Oct 21:122:232-246. doi: 10.1016/j.ejmech.2016.06.035.
Rashmi Gaur 1,  Anup Singh Pathania 2,  Fayaz Ahmad Malik 3,  Rajendra Singh Bhakuni 4,  Ram Kishor Verma 5
Affiliations

Affiliations

  • 1 Medicinal Chemistry Department, Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India.
  • 2 Department of Cancer Pharmacology, Indian Institute of Integrative Medicine, Canal Road Jammu, Jammu and Kashmir, 180001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India.
  • 3 Department of Cancer Pharmacology, Indian Institute of Integrative Medicine, Canal Road Jammu, Jammu and Kashmir, 180001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India. Electronic address: fmalik@iiim.ac.in.
  • 4 Medicinal Chemistry Department, Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110001, India. Electronic address: bhakunirs2000@gmail.com.
  • 5 Medicinal Chemistry Department, Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India.
PMID: 27371926 DOI: 10.1016/j.ejmech.2016.06.035
Abstract

A new series of monomer and dimer derivatives of dihydroartemisinin (DHA) containing substituted Chalcones as a linker were synthesized and investigated for their cytotoxicity in human Cancer cell lines HL-60 (leukemia), Mia PaCa-2 (pancreatic Cancer), PC-3 (prostate Cancer), LS180 (colon Cancer) and HEPG2 (hepatocellular carcinoma). Some of these derivatives have greater antiproliferative and cytotoxic effects in tested cell lines than parent compound DHA. The structures of the all compounds were confirmed by IR, (1)H NMR and mass spectral data. Among the new derivatives, compounds 8, 14, 15, 20 and 24 were found to be more active than parent DHA against tested human Cancer cell lines. DHA derivatives were found to be most active in human leukemia cell lines with compounds 8, 14, 15, 20 and 24 showed IC50 values less than 1 μM for 48 h whereas DHA has IC50 value of 2 μM at same time period. The most potent compounds 8 with IC50 = 0.3 μM (at par with doxorubicin (IC50 = 0.3 μM)) and 15 with IC50 = 0.4 μM, of the series, six and three times active than DHA (with IC50 = 2 μM) respectively were selected for further mechanistic work in human leukemia HL-60 cells.

Keywords

Apoptosis; Artemisinin; Leukemia; Monomer and dimer; Synthesis.

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