title: Schistosomicidal and molluscicidal activities of aminoalkylamino substituted neo- and norneocryptolepine derivatives.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  Evaluation for the first time of a series of chloro- and aminoalkylamino derivatives of neo- and norneocryptolepines for potential schistosomicidal and molluscicidal activities.
  
  
  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.
  
  
  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.
authors.affiliation: Department of Medical Malacology and Schistosome Biological Supply Centre, Theodor Bilharz Research Institute, Imbaba, Egypt. samiaelbardicy21@yahoo.com
authors.forename: Samia
authors.initials: S
authors.lastname: El Bardicy
authors.forename: Ibrahim
authors.initials: I
authors.lastname: El Sayed
authors.forename: Fouad
authors.initials: F
authors.lastname: Yousif
authors.forename: Pieter
authors.initials: P
authors.lastname: Van der Veken
authors.forename: Achiel
authors.initials: A
authors.lastname: Haemers
authors.forename: Koen
authors.initials: K
authors.lastname: Augustyns
authors.forename: Luc
authors.initials: L
authors.lastname: Pieters
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001700:Biomphalaria / Q000187:drug effects; D031106:Cryptolepis / Q000737:chemistry; D004534:Egypt; D020128:Inhibitory Concentration 50; D007928:Lethal Dose 50; D016488:Medicine, African Traditional; D008975:Molluscacides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D011647:Puerto Rico; D011804:Quinolines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects; D012556:Schistosomicides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000470:Alkaloids; D008975:Molluscacides; D011804:Quinolines; D012556:Schistosomicides; C414982:neocryptolepine