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Neocryptolepine analogues containing N-substituted side-chains at C-11: synthesis and antischistosomicidal activity

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Abstract

A set of aminosubstituted neocryptolepine (5-methyl-5H-indolo[2,3-b]quinoline) derivatives has been synthesized and evaluated for in vitro activity against Schistosoma mansoni adult worms. Six out of 18 derivatives showed significant antischistosomal activity with 100% worm mortality at a concentration of 5 μg/ml after 5 days. The most effective compound is neocryptolepine 10d having IC50 and IC90, 2.70 and 3.95 μM/ml for Egyptian Schistosoma strains, respectively. It is clear from the results that introducing N-substituted side-chains into the indoloquinoline core structure significantly increased the antischistosomicidal activity. The structure–activity relationships of this series of compounds are discussed.

Graphical Abstract

Neocryptolepine derivatives containing a basic side-chain at position C-11 were synthesized and evaluated against Egyptian Schistosoma strains. The most active compound 10d showed a significant antischistosomal activity with 100% worm mortality and IC50 of 2.70 μM/ml.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Menoufiya University, Shebin El Koom, Egypt

    Ibrahim El Sayed, Mohamed El Bahanasawy & Mostafa M. Abd El-Sattar

  2. Parasitology Department, Theodor Bilharz Research Institute, Warrak El Hadar, Imbaba, P.O. Box 30, Giza, 12411, Egypt

    Fatem Ramzy & Samia William

Authors
  1. Ibrahim El Sayed
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  2. Fatem Ramzy
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  3. Samia William
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  4. Mohamed El Bahanasawy
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  5. Mostafa M. Abd El-Sattar
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Correspondence to Ibrahim El Sayed.

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Sayed, I.E., Ramzy, F., William, S. et al. Neocryptolepine analogues containing N-substituted side-chains at C-11: synthesis and antischistosomicidal activity. Med Chem Res 21, 4219–4229 (2012). https://doi.org/10.1007/s00044-011-9934-4

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  • DOI: https://doi.org/10.1007/s00044-011-9934-4

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