Synthesis and evaluation of the in vitro and in vivo antitrypanosomal activity of 2-styrylquinolines

Abstract

In this study, we report the synthesis and evaluation of in vitro and in vivo antitrypanosomal activity of styrylquinoline-like compounds (SQ) 3a-h . Synthesis was carried out by using quinaldine and 8- hydroxyquinaldine with a variety of aromatic aldehydes. The structure of SQs was corroborated by one and two-dimension NMR spectroscopy. In vitro antitrypanosomal activity on T. cruzi Talahuen strain was evaluated using β-galactosidase enzymatic method; cytotoxicity on U-937 cells was assessed by using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] method. On the other hand, in vivo therapeutical response to 3a-f compounds was evaluated in BALB/c mice ( Mus musculus ) experimentally infected with T. cruzi blood trypomastigotes and then orally administered with 100 mg/kg weight day for 20 days. All of the compounds showed in vitro activity with EC 50 values ranging between 4.6 ± 0.1 μg/mL (14.4 μM) and 36.6 ± 6.1 μg/mL (91 μM). Furthermore, treatment with 3a-f compounds for 20 days resulted in improvement in all of the mice, with a 83–96% decrease in parasitic load at day 90 post-treatment. Treatment with benznidazol (BZ) managed to cure 100% of the mice at the end of treatment. None of the treatments affected the weight of the animals or alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatinine levels in serum. These results suggest a therapeutic potential of 3a-f compounds as treatment for the infection.

Screening of the antileishmanial and antiplasmodial potential of synthetic 2-arylquinoline analogs

“…Likewise, structural conditions that contribute to the biological activity of this type of compounds are reported, such as: having an unsaturated structure, an alkyl chain length of no more than 5 carbons and the presence of functional groups in the substituents without shared electrons. 12,16,17,72,73 . Furthermore, it has been shown that quinoline derivatives show antileishmanial activity through causing mitochondrial oxidative stress to the parasite 2 .…”

“…The organic phase was dried over anhydrous sodium sulphate, ltered, and concentrated under reduced pressure. Then, the crude product was puri ed by column chromatography (CC), using petroleum benzine/ethyl acetate with an increasing polarity gradient as eluent 12,17,19 4 Hz, H 2' ), 7.28 (d, 1H, J = 9.0 Hz, Ar -H 3" ), 7.81 (dt, 1H, J = 8.3; 10.2 Hz, Ar-H 4" ), 7.34 (dt, 1H, J = 6.1; 6.8 Hz, Ar -H 5" ), 7.14 (dd, 1H, J = 7.8; 7.9 Hz, Ar -H 6" ), 13…”

“…Quinoline nucleus compounds belong to a group of nitrogenated heterocyclic which stand out for their wide range of pharmacological functions 9 , such as antiparasitic activity against protozoans like P. falciparum 11 , 4nitrostyrylquinolines with antiplasmodic activity and excellent selectivity exhibit a cellular action different to current antiplasmodic, acting at the early intraerythrocytic life cycle of malaria parasite, including merozoite invasion with antitrypanosomial and leishmanicide activity 5,12 . In respect to the latter, 8-aminoquinoline (Sitamaquine) has been considered a potential candidate for oral administration 13 .…”

Alternative Approaches for the Treatment of Chagas Disease

“…[151] In 2021, Espinosa et al synthesized 2-styrylquinolines, finding that compound 8 exhibited promising results with an IC 50 value of 28.8 μM. [152] In the same year, Haroon et al synthesized and evaluated 1,3-thiazoles derivative, discovered that compound 9 exhibited a significantly lower IC 50 value of 0.83 μM, eradicating half of the trypomastigote parasite population at an impressively low concentration of 0.830 μM (Figure 4). [153] Filho et al (2021) synthesized and evaluated chlorinesubstituted 4-thiazolidinones, highlighting compound 10, displaying a good IC 50 of 0.85 μM, as a promising candidates for the treatment of T. cruzi infections.. [154] In 2021, Martín-Escolano et al conducted a comprehensive investigation on selenium derivatives as a potential therapeutic intervention for CD, revealing that in vitro study of compound 11 showing potential activity with an IC 50 value of 2.4 � 0.3 μM.…”

Chemopreventive Effect on Human Colon Adenocarcinoma Cells of Styrylquinolines: Synthesis, Cytotoxicity, Proapoptotic Effect and Molecular Docking Analysis

“…This has allowed for the generation of new compounds that have shown greater safety, effectiveness at low doses, and tolerability to treatment due to improvements in pharmacokinetic properties and reductions in adverse effects related to the toxicity produced by the administration of multiple drugs [ 21 , 22 ]. An example of these hybrid compounds are the styrylquinolines, each comprising a quinoline nucleus attached to a styryl group ( Figure 1 ), which have aroused significant interest in recent years given their potential as antiparasitic and antitumor agents [ 23 , 24 , 25 ]. However, there is not enough information about the mechanisms of action carried out by these hybrid compounds to exert their antitumor effect, specifically on colon cancer cells.…”