Exploring Synthetic Dihydrobenzofuran and Benzofuran Neolignans as Antiprotozoal Agents against Trypanosoma cruzi

Abstract

Chagas disease is a neglected tropical disease that affects more than 8 million people. Although there are therapies against this disease, the search for new drugs is important because the current treatments show limited effectiveness and high toxicity. In this work, eighteen dihydrobenzofuran-type neolignans (DBNs) and two benzofuran-type neolignans (BNs) were synthesized and evaluated against amastigote forms of two Trypanosoma cruzi strains. The in vitro cytotoxicity and hemolytic activity of the most active compounds were also evaluated and their relationships with T. cruzi tubulin DBNs were investigated by an in silico approach. Four DBNs demonstrated activity against the T. cruzi Tulahuen lac-Z strain (IC50 from 7.96 to 21.12 µM), and DBN 1 exhibited the highest activity against the amastigote forms of the T. cruzi Y strain (IC50 3.26 μM). Compounds 1–4 showed CC50 values higher than antitrypanosomal activities, except for DBN 3. All DBNs with antitrypanosomal activity demonstrated CH50 higher than 100 µM. The in silico results indicated that DBNs 1, 2, and 4 are capable of destabilizing the dynamics of the tubulin-microtubule from the vinca site. These compounds displayed promising in vitro activity against T. cruzi, especially compound 1, and can be considered molecular prototypes for the development of new antiparasitic drugs.

In vitro Evaluation of the Antileishmanial and Antischistosomal Activities of p‐Coumaric Acid Prenylated Derivatives

“…[16][17][18] Data on the antileishmanial and antischistosomal activity of prenylated p-coumaric acids are scarce. [5,6,19] Thus, as part of our interest in the antiparasitic activities of synthetic [20,21] and natural products, [22,23] we have investigated the in vitro antileishmanial and schistosomal activities of eight prenylated derivatives of p-coumaric acid against Leishmania amazonensis and Schistosoma mansoni.…”

A Comprehensive Review on Benzofuran Synthesis Featuring Innovative and Catalytic Strategies

“…Benzofuran derivatives have been found to be active against bacterial, 5 − 9 viral, 10 , 11 inflammatory, 12 and protozoal diseases. 13 For example, diabetes, 14 HIV, tuberculosis, 15 epilepsy, 16 and Alzheimer’s disease 17 are some of the most common and widely occurring diseases, against which benzofuran derivatives have been known to play a therapeutic role. In addition, these are effective against a variety of cancers 18 − 21 and are also employed as efficient pain killers.…”

In vitro evaluation of the antiparasitic activity of p-coumaric acid prenylated derivatives

“…License: CC BY-NC-ND 4.0 Data on the antileishmanial and antischistosomal activity of prenylated p-coumaric acids are scarce. [5,6,19] Thus, as part of our interest in the antiparasitic activities of synthetic [20,21] and natural products, [22,23] we have investigated the in vitro antileishmanial and schistosomal activity of some prenylated derivatives of p-coumaric acid against Leishmania amazonensis and Schistosoma mansoni.…”