Synthesis and biological evaluation of new amino acid and dipeptide derivatives of neocryptolepine as anticancer agents

Journal of Medicinal Chemistry
Katarzyna SidorykW Peczyńska-Czoch

Abstract

The syntheses of neocryptolepine derivatives containing an amino acid or a dipeptide at the C-9 position and their evaluation for antitumor activity in vitro and in vivo are reported. To establish the influence of an amino acid or a peptide on the physicochemical properties of 5H-indolo[2,3-b]quinoline (DiMIQ), lipophilic and hemolytic properties were investigated. Most of the compounds displayed a high antiproliferative activity in vitro and strongly inhibited growth of tumor in mice compared to cyclophosphamide. The attachment of the hydrophilic amino acid or the peptide to the hydrophobic DiMIQ increased its hydrophilic properties and decreased its hemolytic activity. The glycylglycine conjugate (7a) was the most promising derivative. It strongly inhibited the growth of the tumor in mice (at dose 50 mg kg(-1) day(-1) it inhibited the tumor growth by 46-63% on days 11-16 and by 29-43% on days 18-23) and significantly decreased hemolytic activity and lowered the in vivo toxicity compared to DiMIQ.

References

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Citations

Apr 2, 2014·European Journal of Medicinal Chemistry·Katarzyna SidorykŁukasz Kaczmarek
Nov 21, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Li WangTsutomu Inokuchi
Jul 31, 2014·European Journal of Medicinal Chemistry·Obaid AfzalSandhya Bawa
Mar 27, 2018·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·Krzysztof Z ŁączkowskiJoanna Białczyk
Aug 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Katarzyna SidorykJan Doubsky

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