In Vitro Effects of the Neolignan 2,3‐Dihydrobenzofuran Against Leishmania Amazonensis

Abstract

Leishmaniasis is an infectious disease complex caused by protozoa from the Leishmania genus, which presents a broad spectrum of clinical manifestations: cutaneous, mucocutaneous and visceral forms. The current treatments are unsatisfactory considering that few drugs are available and present some level of toxicity. Many lignans and neolignans have been used for the development of new antileishmania drugs. The capability in vitro of the neolignan 2,3-dihydrobenzofuran (2,3-DBF), a commonly found constituent of propolis and other plants, to inhibit the growth of promastigote and macrophage-internalized amastigote forms of Leishmania amazonensis was investigated. The cytotoxicity of this compound was assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) test in BALB/c murine macrophages and human erythrocyte lysis assay. The 2,3-DBF was active against promastigote (IC 50 =1.042 lM) and amastigote (IC 50 =1.43 lM) forms, indicating a potent antileishmanial effect. There was no evidence of cytotoxicity to macrophages or erythrocytes at concentrations ranging from 13 to 0.5 lM, after 48 hr of exposure. The antileishmanial activity is probably mediated by the activation of macrophages, because treatment with 2,3-DBF increases both phagocytic and lysosomal activities, as well as the nitrite (NO 2 À ) levels. These results suggest that 2,3-DBF may be a potential candidate for the development of a new promising antileishmanial drug. Further studies are needed to determine its potential in vivo effect as well as additional mechanisms underlying the antileishmanial and immunomodulatory activities.

Antileishmanial Activity, Cytotoxicity and Mechanism of Action of Clioquinol Against Leishmania infantum and Leishmania amazonensis Species

“…Plants constitute an important source of new pharmaceuticals, and studies have been developed in an attempt to identify the bioactive molecules that could be employed for this purpose, such as quinoline, alkaloids, coumarins, tannins, saponins, cyclosporine, among others . As a consequence, an increasing awareness of the potential of these compounds might lead to the development of novel drugs for the treatment of neglected diseases, as the impact of natural products on drug discovery is considerable, not only for cancer, but also for parasitic infections .…”

Licarin A, a neolignan isolated from Nectandra oppositifolia Nees & Mart. (Lauraceae), exhibited moderate preclinical efficacy against Schistosoma mansoni infection

“…Interestingly, a low cytotoxic potential was observed for LIC‐A on mammalian cell line (Vero), which is in accordance to recently observations on Vero cells and other cell lines (Meleti et al, 2020; Morais et al, 2020). The interest in neolignans have increased since they exhibit low toxicity potential (de Castro Oliveira et al, 2017; Dias et al, 2017; Zálešák, Bon, & Pospíšil, 2019). Considering a higher selectivity index for the parasite compared with the mammalian cells, the results obtained in the present study reinforce the potential relevance of LIC‐A against S. mansoni .…”

Proximate Analysis and Phytochemical Profile of Brachystegia eurycoma Leaves

“…Hydroquinone occurs naturally in various medicinal plants [61,62], it has been reported to be allelochemic, antimicrobial, antihepatomic, antilithic, antimelanomic, antimelasmic, uroantiseptic , antimitotic, and antipertussive [63][64][65]. Benzofuran, 2,3-dihydro is a coumaran and research has shown that it possesses antiinflammatory, antidiarrheal, antileishmanial, immunomodulatory, antimicrobial and antihelminthic activities [66][67][68]. Octadecanoic acid is a flavouring agent which is hypocholesterolemic [69].…”