2. Academic Validation
  3. Design, synthesis and biological evaluation of new pyrrolidine carboxamide analogues as potential chemotherapeutic agents for hepatocellular carcinoma

Design, synthesis and biological evaluation of new pyrrolidine carboxamide analogues as potential chemotherapeutic agents for hepatocellular carcinoma

  • Eur J Med Chem. 2017 Oct 20:139:804-814. doi: 10.1016/j.ejmech.2017.08.054.
Hany A Omar 1,  Dana M Zaher 2,  Vunnam Srinivasulu 2,  Fatema Hersi 2,  Hamadeh Tarazi 3,  Taleb H Al-Tel 4
Affiliations

Affiliations

  • 1 Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates; College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
  • 2 Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates.
  • 3 Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates; College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates.
  • 4 Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates; College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates. Electronic address: taltal@sharjah.ac.ae.
PMID: 28865276 DOI: 10.1016/j.ejmech.2017.08.054
Abstract

The successful targeting of different malignancies by OSU-2S, encouraged us to design and synthesize a novel series of pyrrolidine aryl carboxamide derivatives. In this context, we found that, the amide nature and tether length were found to be key determinant elements for the Anticancer activity of these new and rigid analogues of OSU-2S. The most effective analogues induced Apoptosis in Cancer cells by a similar mechanism to that of OSU-2S, possibly via the activation of PKCδ in addition to their ability to induce cell cycle arrest and inhibition of Cancer cell migration. Compound 10m, possesses Anticancer potency comparable to that of OSU-2S when tested against Cancer cell lines under study, and was found to be safer on normal cells. Furthermore, compound 10m, was found to be about 2-folds more potent than the Anticancer drug Sorafenib in hepatocellular carcinoma (HCC). The newly developed compounds represent a therapeutically promising approach for the treatment of HCC.

Keywords

Anticancer; Hepatocellular carcinoma; OSU-2S; PKCδ; Pyrrolidine carboxamide.

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