Planta Med 2015; 81 - PM_84
DOI: 10.1055/s-0035-1565461

Synthesis and biological evaluation of 1,3,6-trisubstituted β-carboline derivatives for cytotoxic and anti-leishmanial potential

NA Lunagariya 1, VM Gohil 1, V Kushwah 2, S Neelagiri 3, S Jain 2, S Singh 3, K Kumar Bhutani 1
  • 1Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab-160062, INDIA, S.A.S. Nagar, India
  • 2Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab-160062, INDIA, S.A.S. Nagar, India
  • 3Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab-160062, INDIA, S.A.S. Nagar, India

β-carbolines have been a privileged natural product scaffold for developing potent anti-cancer and anti-leishmanial compounds. [1] β-carbolines modified at C1, C3, N2 & N9 have been reported with increased cytotoxicity towards cancer cells. [2] Recent reports suggest that substitution on A-ring improves cytotoxicity towards cancer cells and inhibition of kinases. [2 – 4] With this background, 23 β-carbolines were synthesized and screened for cytotoxic and anti-leishmanial potential. 1-methyl & 3-methoxycarbonyl substitutions were selected based on literature [5], while C6-substitution was kept variable. Compounds 13c & 13q showed potent cytotoxicity as compared to docetaxel in four human cancer cell lines and induced apoptosis in A-549 and MCF-7. SAR suggests that the bulky substitution on benzamido group favors the cytotoxicity. However, increased IC50 in in vitro anti-leishmanial assay suggests that C6-substitution was found to be unfavorable. These lead compounds need to be further optimized for more potent molecules.

Fig. 1 (PM-84)

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