Synthesis, antioxidant and antichagasic properties of a selected series of hydroxy-3-arylcoumarins

Robledo-O’Ryan, Natalia; Matos, María Joäo; Vázquez-Rodríguez, Saleta; Santana, Lourdes; Uriarte, Eugenio; Moncada‐Basualto, Mauricio; Mura, Francisco; Lapier, Michel; Maya, Juan Diego; Olea‐Azar, Claudio

doi:10.1016/j.bmc.2016.11.033

Cited by 36 publications

(20 citation statements)

References 37 publications

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“…List of synthesized compounds: 7,8-dihydroxy-3-phenylcoumarin 2 [26], 7,8-dihydroxy-3-(3-hydroxyphenyl)coumarin 3 [28], 7,8-dihydroxy-3-(2-hydroxyphenyl)coumarin 4 [28], 3-(3,4-dihydroxyphenyl)-7,8-dihydroxycoumarin 5 [28], 7,8-dihydroxy-3-(thiophen-3-yl)coumarin 6 [26], 3-(4-bromothiophen-2-yl)-7,8-dihydroxycoumarin 7 [29], 5,7-dihydroxy-3-phenylcoumarin 8 [30], 7-hydroxy-3-phenylcoumarin 9 [31], 8-hydroxy-3-phenylcoumarin 10 [30].…”

Section: Methodsmentioning

confidence: 99%

Antibacterial Activity and Molecular Docking Studies of a Selected Series of Hydroxy-3-arylcoumarins

et al. 2019

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Antibiotic resistance is one of the main public health concerns of this century. This resistance is also associated with oxidative stress, which could contribute to the selection of resistant bacterial strains. Bearing this in mind, and considering that flavonoid compounds are well known for displaying both activities, we investigated a series of hydroxy-3-arylcoumarins with structural features of flavonoids for their antibacterial activity against different bacterial strains. Active compounds showed selectivity against the studied Gram-positive bacteria compared to Gram-negative bacteria. 5,7-Dihydroxy-3-phenylcoumarin (compound 8) displayed the best antibacterial activity against Staphylococcus aureus and Bacillus cereus with minimum inhibitory concentrations (MICs) of 11 g/mL, followed by Staphylococcus aureus (MRSA strain) and Listeria monocytogenes with MICs of 22 and 44 g/mL, respectively. Moreover, molecular docking studies performed on the most active compounds against Staphylococcus aureus tyrosyl-tRNA synthetase and topoisomerase II DNA gyrase revealed the potential binding mode of the ligands to the site of the appropriate targets. Preliminary structure–activity relationship studies showed that the antibacterial activity can be modulated by the presence of the 3-phenyl ring and by the position of the hydroxyl groups at the coumarin scaffold.

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Section: Methodsmentioning

confidence: 99%

Antibacterial Activity and Molecular Docking Studies of a Selected Series of Hydroxy-3-arylcoumarins

et al. 2019

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“…The flagellated protozoan parasite Trypanosoma cruzi causes Chagas disease, also known as American trypanosomiasis. It is estimated that over six million people are infected with T. cruzi worldwide, and this disease represents one of the important health problems in South, Central, and North America [1, 2]. Chagas disease causes almost 12000 deaths annually, while the number of diagnosed cases has increased in nonendemic regions, due to emigration events [3, 4].…”

Section: Introductionmentioning

confidence: 99%

The Correlation between Chemical Structures and Antioxidant, Prooxidant, and Antitrypanosomatid Properties of Flavonoids

Baldim

Alcântara

Domingos

et al. 2017

Oxidative Medicine and Cellular Longevity

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Flavonoids have demonstrated in vivo and in vitro leishmanicidal, trypanocidal, antioxidant, and prooxidant properties. The chemotherapy of trypanosomiasis and leishmaniasis lacks efficacy, presents high toxicity, and is related to the development of drug resistance. Thus, a series of 40 flavonoids were investigated with the purpose of correlating these properties via structure and activity analyses based on integrated networks and QSAR models. The classical groups for the antioxidant activity of flavonoids were combined in order to explain the influence of antioxidant and prooxidant activities on the antiparasitic properties. These analyses become useful for the development of efficient treatments for leishmaniasis and trypanosomiasis. Finally, the dual activity of flavonoids presenting both anti- and prooxidant activities revealed that the existence of a balance between these two features could be important to the development of adequate therapeutic strategies.

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“…In the same year, Vazquez-Rodriguez et al described the synthesis of new coumarin-chalcone hybrids and evaluated their antitrypanosomal activity against epimastigotes, trypomastigotes, and amastigotes of T. cruzi (Vazquez-Rodriguez et al, 2016). Ryan et al recently described the synthesis of hydroxyl-substituted 3-arylcoumarins and evaluated the antichagasic profile of these compounds against the epimastigote form (Robledo-O'Ryan et al, 2017). In order to meet this deficit in new drug candidates for Chagas disease, we have prepared and tested 18 tricyclic coumarins against T. cruzi, evaluated their cytotoxic effect against L929 cells, and determined the selectivity index.…”

mentioning

confidence: 99%

Design, synthesis, molecular modelling, and in vitro evaluation of tricyclic coumarins against Trypanosoma cruzi

et al. 2018

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Chagas disease is caused by infection with the parasite protozoan Trypanosoma cruzi and affects about 8 million people in 21 countries in Latin America. The main form of treatment of this disease is still based on the use of two drugs, benznidazole and nifurtimox, which both present low cure rates in the chronic phase and often have serious side‐effects. Herein, we describe the synthesis of tricyclic coumarins that were obtained via NHC organocatalysis and evaluation of their trypanocidal activity. Molecular docking studies against trypanosomal enzyme triosephosphate isomerase (TIM) were carried out, as well as a theoretical study of the physicochemical parameters. The tricyclic coumarins were tested in vitro against the intracellular forms of Trypanosoma cruzi. Among the 18 compounds tested, 10 were more active than the reference drug benznidazole. The trypanocidal activity of the lead compound was rationalized by molecular docking study which suggested the strong interaction with the enzyme TIM by T. cruzi and therefore indicating a possible mode of action. Furthermore, the selectivity index of eight tricyclic coumarins with high anti‐T. cruzi activity was above 50 and thus showing that these lead compounds are viable candidates for further in vivo assays.

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Synthesis, antioxidant and antichagasic properties of a selected series of hydroxy-3-arylcoumarins

Cited by 36 publications

References 37 publications

Antibacterial Activity and Molecular Docking Studies of a Selected Series of Hydroxy-3-arylcoumarins

Antibacterial Activity and Molecular Docking Studies of a Selected Series of Hydroxy-3-arylcoumarins

The Correlation between Chemical Structures and Antioxidant, Prooxidant, and Antitrypanosomatid Properties of Flavonoids

Design, synthesis, molecular modelling, and in vitro evaluation of tricyclic coumarins against Trypanosoma cruzi

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