Unsymmetrical 1,5-diaryl-3-oxo-1,4-pentadienyls and their evaluation as antiparasitic agents

Din, Zia Ud; Fill, Taícia Pacheco; Assis, Francisco F. de; Lazarin‐Bidóia, Danielle; Kaplum, Vanessa; Garcia, Francielle P.; Nakamura, Celso Vataru; Oliveira, Kléber T. de; Rodrigues‐Filho, Edson

doi:10.1016/j.bmc.2013.12.020

Cited by 23 publications

(13 citation statements)

References 37 publications

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“…The compound (1 E ,4 E )-2-methyl-1,5-bis(4-nitrophenyl)penta-1,4-dien-3-one (A3K2A3) (Figure 1) is dibenzylideneacetone synthesized following the methodology described by Din et al [26]. Stock solution of the compound was prepared aseptically in DMSO and diluted in culture medium so that the DMSO concentration did not exceed 1% in the experiments.…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, DBA potentiates TRAIL-induced apoptosis through downregulation of cell survival proteins and upregulation of death receptors via activation of reactive oxygen species (ROS) [25]. Recently, our research group reported trypanocidal activity of a DBA (1 E ,4 E )-2-methyl-1,5-bis(4-nitrophenyl)penta-1,4-dien-3-one (A3K2A3) against epimastigote and trypomastigote forms of T. cruzi [26]. …”

Section: Introductionmentioning

confidence: 99%

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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

Peron

Lazarin‐Bidóia

Din

et al. 2017

BioMed Research International

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Peron

Lazarin‐Bidóia

Din

et al. 2017

BioMed Research International

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“…The compounds (1E,4E)-2-methyl-1-(4-nitrophenyl)-5-phenylpenta-1,4-dien-3-one (A3K2A1) and (1E,4E)-2-methyl-1,5-bis(4-nitrophenyl)penta-1,4-dien-3-one (A3K2A3) were synthesized as previously described by Ud Din et al (15). The molecular structures of the compounds are shown in Fig.…”

Section: Methodsmentioning

confidence: 99%

“…The three forms of T. cruzi were treated with the compounds at concentrations that correspond to the IC 50 s (concentrations that inhibited 50% of the parasites) previously determined (15 MD, USA) in DMEM supplemented with 2 mM L-glutamine and 10% FBS and buffered with sodium bicarbonate in a 5% CO 2 -air mixture at 37°C (17). Trypomastigotes and amastigotes were separated by differential centrifugation at 850 ϫ g for 5 min.…”

Section: Methodsmentioning

confidence: 99%

“…Some studies have demonstrated the chemotherapeutic properties of DBAs, including antiplasmodial (10) and anticancer (11,12,13,14) effects. Our research group recently tested a library of new DBAs against T. cruzi and Leishmania amazonensis and reported interesting results (15). (1E,4E)-2-Methyl-1-(4-nitrophenyl)-5-phenylpenta-1,4-dien-3-one (A3K2A1) and (1E,4E)-2-methyl-1, 5-bis(4-nitrophenyl)penta-1,4-dien-3-one (A3K2A3) were the most active compounds against T. cruzi.…”

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Dibenzylideneacetones Are Potent Trypanocidal Compounds That Affect the Trypanosoma cruzi Redox System

Lazarin-Bidóia

Desoti

Martins

et al. 2016

Antimicrob Agents Chemother

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Despite ongoing efforts, the available treatments for Chagas' disease are still unsatisfactory, especially in the chronic phase of the disease. Our previous study reported the strong trypanocidal activity of the dibenzylideneacetones A3K2A1 and A3K2A3 against Trypanosoma cruzi (Z. Ud Din, T. P. Fill, F. F. de Assis, D. Lazarin-Bidóia, V. Kaplum, F. P. Garcia, C. V. Nakamura, K. T. de Oliveira, and E. Rodrigues-Filho, Bioorg Med Chem 22:1121-1127, 2014, http://dx.doi.org/10.1016/j.bmc.2013.12.020). In the present study, we investigated the mechanisms of action of these compounds that are involved in parasite death. We showed that A3K2A1 and A3K2A3 induced oxidative stress in the three parasitic forms, especially trypomastigotes, reflected by an increase in oxidant species production and depletion of the endogenous antioxidant system. This oxidative imbalance culminated in damage in essential cell structures of T. cruzi, reflected by lipid peroxidation and DNA fragmentation. Consequently, A3K2A1 and A3K2A3 induced vital alterations in T. cruzi, leading to parasite death through the three pathways, apoptosis, autophagy, and necrosis.

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Diarylpentanoids, the privileged scaffolds in antimalarial and anti‐infectives drug discovery: A review

Ramli,

Mohd Faudzi

2023

Archiv der Pharmazie

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Asia is a hotspot for infectious diseases, including malaria, dengue fever, tuberculosis, and the pandemic COVID‐19. Emerging infectious diseases have taken a heavy toll on public health and the economy and have been recognized as a major cause of morbidity and mortality, particularly in Southeast Asia. Infectious disease control is a major challenge, but many surveillance systems and control strategies have been developed and implemented. These include vector control, combination therapies, vaccine development, and the development of new anti‐infectives. Numerous newly discovered agents with pharmacological anti‐infective potential are being actively and extensively studied for their bioactivity, toxicity, selectivity, and mode of action, but many molecules lose their efficacy over time due to resistance developments. These facts justify the great importance of the search for new, effective, and safe anti‐infectives. Diarylpentanoids, a curcumin derivative, have been developed as an alternative with better bioavailability and metabolism as a therapeutic agent. In this review, the mechanisms of action and potential targets of antimalarial drugs as well as the classes of antimalarial drugs are presented. The bioactivity of diarylpentanoids as a potential scaffold for a new class of anti‐infectives and their structure–activity relationships are also discussed in detail.

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Unsymmetrical 1,5-diaryl-3-oxo-1,4-pentadienyls and their evaluation as antiparasitic agents

Cited by 23 publications

References 37 publications

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

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

Dibenzylideneacetones Are Potent Trypanocidal Compounds That Affect the Trypanosoma cruzi Redox System

Diarylpentanoids, the privileged scaffolds in antimalarial and anti‐infectives drug discovery: A review

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