Literature DB >> 22338119

Schistosomicidal and molluscicidal activities of aminoalkylamino substituted neo- and norneocryptolepine derivatives.

Samia El Bardicy1, Ibrahim El Sayed, Fouad Yousif, Pieter Van der Veken, Achiel Haemers, Koen Augustyns, Luc Pieters.   

Abstract

CONTEXT: The cryptolepines originate from the roots of the climbing shrub Cryptolepis sanguinolenta (Lindi) Schitr(Periplocaeae) which is used in Central and West Africa in traditional medicine for the treatment of malaria.
OBJECTIVES: Evaluation for the first time of a series of chloro- and aminoalkylamino derivatives of neo- and norneocryptolepines for potential schistosomicidal and molluscicidal activities.
MATERIALS AND METHODS: A series of chloro- and aminoalkylamino substituted neo- and norneocryptolepine derivatives were synthesized. They were tested in vitro against viable Schistosoma mansoni Sambon mature worms in culturemedium with fetal serum and antibiotics and in dechlorinated water against the snail vector Biomphalaria alexandrina Ehrenberg. Active compounds were further subjected to determination of their IC50 values.
RESULTS: Results showed that six neocryptolepine and two norneocryptolepine derivatives had in vitro schistosomicidal activity on Egyptian and Puerto Rican strains of S. mansoni. The most effective derivative (2-chloro-5-methyl-N-(2-morpholin-4-ethyl)-5H-indolo[2,3b]quinoline-11-amine) has IC50 and IC90 1.26 and 4.05 μM and 3.54 and 6.83 μM with the Egyptian and Puerto Rican strains of Schistosoma, respectively. All eight derivatives showed molluscicidal activity against the vector snail B. alexandrina. The most active compound (2-chloro-11-(4-methylpiperazin-1-yl)-6H-indolo[2,3-b] quinoline) has LC50 0.6 and LC90 3.9 ppm after 24 h. DISCUSSION AND
CONCLUSIONS: The findings demonstrate that introducing chloro- and aminoalkylamino side chain initiated both schistosomicidal and molluscicidal activities in these derivatives. The structure–activity relationship of this series of compounds is discussed.

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Year:  2012        PMID: 22338119     DOI: 10.3109/13880209.2011.578278

Source DB:  PubMed          Journal:  Pharm Biol        ISSN: 1388-0209            Impact factor:   3.503


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