Antileishmanial activity of a formulation of 2-n-propylquinoline by oral route in mice model

Abstract

2-n-propylquinoline is presently a drug-candidate for the treatment of visceral leishmaniosis in pre-clinical development. As this compound is in an oily state, it needs to be formulated and the objectives of this study are: to prepare a formulation; to demonstrate that the new salted formulation did not alter the activity of the active ingredient; and finally, that this activity was quite good compared to the reference oral drug, miltefosine. Therefore, a 2-n-propylquinoline formulation, as camphorsulfonic salt, was prepared and characterised. On the Leishmania donovani / Balb/c mice model, a treatment by oral route at 60 μmoles/kg/day for ten consecutive days with this formulation was compared to 2-n-propylquinoline alone and to miltefosine, the oral reference drug. The salt formulation did not alter the activity of the 2-n-propylquinoline. The formulation reduced the parasite burden of 76% compared to 89% for miltefosine (not significant). The characteristics of this formulation results in a suitable drugability of 2-n-propylquinoline for further studies.

Virtual screen for repurposing approved and experimental drugs for candidate inhibitors of EBOLA virus infection

“…Six 2-alkylquinolines have been also included in this study. This chemical series is promising as some derivatives exhibited antiviral activity such as 2PQ, and 2QQ 32 , 33 antimalarial activity such as 2PQ and 2PentQ2 34 , antileishmanial activity such as 2PQ 35 , 36 and neurotrophin-like activity on dopaminergic neurons such as 2QI15 37 . These compounds exhibit some advantages in regard to their chemical synthesis with few steps and good yields as well as their chemical stability in tropical conditions of storage.…”

Investigational drugs for visceral leishmaniasis

“…In vivo studies in Balb/c mice model, oral treatment at 60 mmoles/kg/day for 10 days with this formulation was compared to 2-n-propylquinoline alone and to miltefosine. The salt formulation did not alter the activity of the 2-n-propylquinoline and reduced the parasite burden 76% compared to 89% for miltefosine 76 .…”

Recent synthetic efforts in the preparation of 2-(3,4)-alkenyl (aryl) quinoline molecules towards anti-kinetoplastid agents

“…Chimanine alkaloids models, especially chimanine B [2-(E)prop-1 0 -enylquinoline], 2-n-propylquinoline and 2-phenylquinoline have been used in order to nd some quinoline structure-antitrypanosomal activity relations and more than 300 mono-substituted quinoline compounds of types I-IV have been 38,[44][45][46] have been easily prepared from quinoline 2 or 2-methylquinoline 3 using reactions of quinoline-N-oxide 5 activated by iso-butyl chloroformate and Grignard reagents or Wittig reactions of 2quinaldehyde 6 and respective Wittig reagents 36,37,47,48 (Scheme 3).…”

“…Thus, this simple quinoline is currently a drug-candidate for the treatment of visceral leishmaniasis in pre-clinical development. 45 As this compound is in an oily state, it was developed some formulations (as camphorsulfonic salt and hydroxypropyl beta-cyclodextrin/2-n-propylquinoline mixture) that are compatible with an intravenous administration and did not alter the activity of the active ingredient. 45,46 One serious shortcoming of these reactions is the laborious procedure for the isolation of the quinoline derivatives from the reaction mixture.…”