Synthesis and trypanocidal activity of salicylhydrazones and p-tosylhydrazones of S-(+)-carvone and arylketones on African trypanosomiasis

Bienvenu Glinma,D.S Kpoviessi,Fernand Gbaguidi,Alban Houngbeme,Horrhus Houngue,Jacques Poupaert,Georges Accrombessi,Salom Eacute,Urbain Kassehin

doi:10.7324/japs.2015.50601

Abstract

Hydrazones are nowadays considered to be good candidates for various pharmaceutical applications. Here, we have synthesized two series of hydrazones: salicylhydrazones (GS1-4) and p-tosylhydrazones (GT1-4) from S-(+)-carvone and three aryketones with good yields (57-91%). Molecules were characterized by elemental analyses; TLC, NMR 1H, NMR 13C and MS. Submitted, in vitro, to their antiparasitic testing on Trypanosoma brucei brucei, and toxicity on Artemia salina Leach, all compounds except GT2 showed significant antitrypanosomal activity IC50 ranging from 1 to 34 micromolar (µM). Among them, 2-acetynaphthalene salicylhydrazone GS4 (IC50 = 1.97 ± 0.42 µM) and 7-methoxy-1-tetralone p-tosylhydrazone GT3 (IC50 =7.98 ± 1.65 µM) exhibited good trypanocidal activity and the other are moderates on parasite; when the compounds GS1, GT3 and GT4 presented toxic activity on larvae. In agreement to their selectivity index, which is greater than 1 (SI > 1), products turn out quite selective on the parasite: a series of salicylhydrazones revealed more selective (SI ≥ 11), especially GS4 (SI = 157) than the series of p-tosylhydrazones showed 1 ≤ SI ≤ 22. The synthesized compounds clearly displayed significant selective pharmaceutical activities on the parasite tested. Compounds developing could open promising route to news drug-candidates.

Highlights

Hydrazides and hydrazones are nowadays an important class of biologically active compounds (Ali et al, 2012; Narasimhan et al, 2010)
The reactions are followed in Thin Layer chromatography (TLC), the product is dissolved in chloroform and the eluent is composed of a mixture of hexane / ethyl acetate (Hex / EtOAc v / v: 7/3 ; 8/2)
It was described in 1976 the synthesis of acetophenone p-tosylhydrazone without catalyst for 5.5 hours with 68% yield (Ashraf, 1976); the synthesis using benzaldehyde salicylic acid hydrazide and 4-dimethylaminobenzaldehyde or 4nitrobenzaldehyde for 4 hours (Al-Ajrawy, 2011)

Summary

INTRODUCTION

Hydrazides and hydrazones are nowadays an important class of biologically active compounds (Ali et al, 2012; Narasimhan et al, 2010). They exhibit a wide range of interesting pharmaceutical derivatives and are important intermediates in organic synthesis (Rollas et al, 2007). Hydrazideshydrazones are used as analytical reagents, a polymer coating of ink, pigments and fluorescent materials (El-Tabl et al, 2008) These molecules are known possessing several interesting biological properties, among others, antibacterial (Özkay et al, 2010; Bedia et al, 2006), anticonvulsant (Kaushik et al, 2010), antitrypanosomal (Troeberg et al, 2000), anti-fungal (Cui et al, 2011, Loncle et al, 2004), antipyretic (Cocco et al, 2006), malaria (Xia et al, 2008).

MATERIALS AND METHODS

RESULTS AND DISCUSSION

CONCLUSION