Effects of (1E,4E)-2-Methyl-1,5-bis(4-nitrophenyl)penta-1,4-dien-3-one onTrypanosoma cruziand Its Combinational Effect with Benznidazole, Ketoconazole, or Fluconazole

Abstract

This study reports the activity induced by (1E,4E)-2-methyl-1,5-bis(4-nitrophenyl)penta-1,4-dien-3-one (A3K2A3) against Trypanosoma cruzi. This compound showed trypanocidal activity against the multiplicative epimastigote and amastigote forms of this protozoan, with IC50 values of 1.99 ± 0.17 and 1.20 ± 0.16 μM, respectively, and EC50 value of 15.57 ± 0.34 μM against trypomastigotes. The combination of A3K2A3 with benznidazole or ketoconazole demonstrated strong synergism, increasing effectiveness against trypomastigotes or epimastigotes of T. cruzi. In addition, the drug combination of A3K2A3 with benznidazole or ketoconazole on LLCMK2 cells demonstrated an antagonist effect, which resulted in greater protection of the cells from drug damage. The combination of the compound with fluconazole was not effective. Transmission and scanning electron micrographs showed changes on parasites, mainly in the cytoplasmatic membrane, nucleus, mitochondrion, and Golgi complex, and a large increase in the number of autophagosome-like structures and lipid-storage bodies, accompanied by volume reduction and rounding of the parasite. A3K2A3 might be a promising compound against T. cruzi.

1H and 13C NMR spectral assignments of twenty‐six 1‐aryl‐5‐(2‐(styryl)phenyl)penta‐1,4‐dien‐3‐ones

“…Oryzae and antiviral activities against tobacco mosaic virus and act as activators of the master gene transcription factor EB; they also display neuroprotective effects and antiparasitic activities against Trypanosoma cruzi . Another polyphenol produced from grapes, resveratrol (3,4′,5‐trihydroxy‐ trans ‐stilbene; Figure d), is known to be a phytoalexin that protects plants from bacteria and fungi . Like curcumin, resveratrol shows diverse biological activities including anticancer, antidiabetes, and antioxidant effects and targets mitochondrial metabolic pathways .…”

Efficacy and Safety of Chagas Disease Drug Therapy and Treatment Perspectives

“…Next, it was evaluated in combination with BNZ, ketoconazole, and fluconazole. Although the combination with the last one was ineffective, the combination with BNZ and ketoconazole demonstrated strong synergism [174].…”

Differential pulse voltammetric determination of benznidazole loaded in nanostructured lipid carriers and urine**

“…This disease has infected approximately seven million people worldwide [4], mainly in endemic areas of continental Latin American countries. Benznidazole [ N ‐benzyl‐(2‐nitroimidazole) acetamide] (BZN) is the only drug available in Brazil and most Latin American countries to treat this disease [5, 6]. It is a nitroimidazole derivative used mainly in the acute phase of the disease; its effect on the chronic phase is still questionable and induces numerous adverse reactions [7].…”