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

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 1 H, NMR 13 C 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.

Study of some carbazones and hydrazones: synthesis, characterization and pharmaceutical properties

“…ESI-MS spectra examinations showed the mass of all compounds. Analysis of data confirms results of the previous studies [11,16,21,[30][31][32] .…”

“…After cooling, the precipitate was filtered, washed with cold distilled water until neutrality, dried and then recrystallized in ethanol. [21] : In a 100 mL flask, we prepare a solution of 0.01 mole of ketone in 20-40 mL of ethanol and 2 mL of glacial acetic acid (GAA) and then we added slowly to a stirring solution a solution of p-tosylhydrazide (1.76 g) dissolved in 10 mL of ethanol. The mixture is maintained at reflux for 2 hours.…”

Design, synthesis, electrochemistry and anti-trypanosomatid hit/lead identification of nitrofuranylazines

“…1 ) that possesses anti-infective activity. The hydrazone moiety also confers diverse biological and pharmacological properties, such as anticancer, 26 antimicrobial, 27 antitrypanosomal, 28 antimycobacterial, 29 anticonvulsive, 30 anti-inflammatory 31 and analgesic properties. 32 Altogether, these pharmacological features enhance the stand of cNFs as potentially repurposable drugs for the treatment of infectious diseases such as leishmaniasis and Chagas disease.…”

Analysis of the Crystal Structure and Energy Frameworks of 5-Acetil-1,3-Dimethyl Barbituric Acid

“…[14][15][16][17][18][19]These coordination compounds synthesized with acetylated pyrimidine derivatives have been the subject of many studies due to their antitumor, anti-cancer, antiosteoporp-free, antimicrobial, anti-inflammatory, antitubercular, anticonvulsant interactions. [7,[20][21][22][23][24][25][26][27][28][29][30][31][32][33] In this study, X-ray quality crystals were obtained after acetylation steps of 1,3 dimethylbarbituric acid compound. The molecular and crystal structures of 5acetyl-1,3 dimethylbarbituric acid (1,3-ABA) were investigated using single crystal analysis, X-ray diffraction technique and various spectroscopic techniques.…”