Schistosomicidal and molluscicidal activities of aminoalkylamino substituted neo- and norneocryptolepine derivatives
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Pharmaceutical biology. - Lisse
, p. 134-140
University of Antwerp
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 culture medium 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 IC(50) 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-a mine) has IC(50) and IC(90) 1.26 and 4.05 mu M and 3.54 and 6.83 mu M 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 LC(50) 0.6 and LC(90) 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.