Synthesis, Structure and In Vitro Anti-Trypanosomal Activity of Non-Toxic Arylpyrrole-Based Chalcone Derivatives

Abstract

With an intention of identifying chalcone derivatives exhibiting anti-protozoal activity, a cohort of relatively unexplored arylpyrrole-based chalcone derivatives were synthesized in moderate to good yields. The resultant compounds were evaluated in vitro for their potential activity against a cultured Trypanosoma brucei brucei 427 strain. Several compounds displayed mostly modest in vitro anti-trypanosomal activity with compounds 10e and 10h emerging as active candidates with IC50 values of 4.09 and 5.11 µM, respectively. More importantly, a concomitant assessment of their activity against a human cervix adenocarcinoma (HeLa) cell line revealed that these compounds are non-toxic.

Hydrazone‐Tethered 5‐(Pyridin‐4‐yl)‐4H‐1,2,4‐triazole‐3‐thiol Hybrids: Synthesis, Characterisation, in silico ADME Studies, and in vitro Antimycobacterial Evaluation and Cytotoxicity

“…Subsequent heating of intermediate 8 (step ii) with hydrazine hydrate in anhydrous pyridine, which simultaneously acted as a solvent and catalyst, yielded 4‐amino‐5‐(pyridine‐4‐yl)‐4 H ‐1,2,4‐triazole‐3‐thiol ( 9 ) in good percentage yield. In parallel, access to the arylpyrrole intermediates 10 a – g was achieved as previously reported [50] …”

“…In parallel, access to the arylpyrrole intermediates 10 a-g was achieved as previously reported. [50] Briefly, condensation of commercially available anilines with 2,5-hexanedione yielded the arylpyrrole intermediates 10 a-g in decent yields. Subsequently, the arylpyrroles 10 a-g were subjected to the Vilsmeier-Haack formylation reaction to produce the desired arylpyrrolecarbaldehydes 11 a-g in quantitative yields, without the need for further purification.…”

Anti-trypanosomal screening of Salvadoran flora

“…Cardamomin (3) has been reported to show trypanocidal activity against Trypanosoma brucei [44]. Synthesis and anti-trypanosomal activity of chalcone derivatives [45,46] and chalconebased compounds [47][48][49] have been reported.…”

Design, Synthesis, and Bioactivity of Chalcone Derivatives Containing Indanone

“…Chalcone exists widely in licorice, safflower, oxytropis falcate bunge, hops, and other plants as an essential natural product and an important intermediate for the synthesis of flavonoids. Chalcone has a wide range of pharmacological activities, such as antibacterial, antiviral, insecticidal, anti-inflammatory, antitumor, antioxidant, and other biological activities, due to its flexibility and ability to bind to a variety of receptors. In addition, chalcone contains α,β-unsaturated carbonyl groups in its structure, which can be conjugated with nucleophilic groups (such as sulfhydryl groups in proteins) in bacteria, viruses, and pests, thus causing them to die …”