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  3. Synthesis of new triterpenic monomers and dimers as potential antiproliferative agents and their molecular docking studies

Synthesis of new triterpenic monomers and dimers as potential antiproliferative agents and their molecular docking studies

  • Eur J Med Chem. 2018 Jan 1;143:948-957. doi: 10.1016/j.ejmech.2017.10.079.
Aasim Saeed 1,  Hidayat Hussain 2,  Umair Shamraiz 1,  Najeeb Ur Rehman 3,  Husain Yar Khan 3,  Amin Badshah 4,  Lucie Heller 5,  René Csuk 5,  Majid Ali 6,  Ajmal Khan 7,  Ahmed Al-Harrasi 8
Affiliations

Affiliations

  • 1 UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Oman; Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
  • 2 UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Oman; Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093-0204, USA. Electronic address: hussainchem3@gmail.com.
  • 3 UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Oman.
  • 4 Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
  • 5 Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str.2, D-06120, Halle (Saale), Germany.
  • 6 Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, KPK, Pakistan.
  • 7 UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Oman; Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, KPK, Pakistan.
  • 8 UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, P.O. Box 33, Birkat Al Mauz, Nizwa 616, Oman. Electronic address: aharrasi@unizwa.edu.om.
PMID: 29232585 DOI: 10.1016/j.ejmech.2017.10.079
Abstract

In the current investigation, new monomers of myrrhanone B and lupeolic acid were prepared via reaction of triterpenic acids with linkers in the presence of K2CO3. In addition, new bis-myrrhanone B homodimers, myrrhanone B-myrrhanol B heterodimers, and bis-myrrhanone β-boswellic acids heterodimer were prepared. Evaluation of these compounds on the proliferation of four different human Cancer cell lines, viz., FaDu (pharynx carcinoma), A2780 (ovarian carcinoma), HT29 (colon adenocarcinoma) and A375 (malignant melanoma) has been performed. It is worth mentioning that compounds 4, 7, 8, 10, and 11 possess potent antiproliferative effect towards HT29 Cancer cells with IC50 values of 8.1 μM, 5.4 μM, 8.8 μM, 6.8 μM, and 8.2 μM, respectively. In addition, these compounds display good to moderate antiproliferative activities towards A2780 and A375 with IC50 values ranging from 10.4 to 24.2 μM. Moreover, the molecular docking studies of most active compounds (4, 7, 8, 10 and 11) with six anti-cancer drug targets DHFR, VEGFR2/KDR/Flk-1, HER-2/neu, CDK6, hCA-IX and LOX also carried, in order to know the mode of binding interaction and energy of this class of compounds.

Keywords

Antiproliferation; Docking study; Myrrhanone B; Triterpene acid.

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