In vivo Antimalarial and Antitrypanosomal Activity of Strychnogucine B, a Bisindole Alkaloid from Strychnos icaja

Abstract

Strychnogucine B is a bisindole alkaloid previously isolated from that possesses promising antiplasmodial properties. This compound was synthesized in four steps from (-)-strychnine. As no acute toxicity was observed at the highest tested cumulative dose of 60 mg/kg, its antimalarial activity was determined intraperitoneally at 30 mg/kg/d in a murine model. In the Peters's 4-d suppressive test, this alkaloid suppressed the parasitaemia by almost 36% on day 5 and 60% on day 7 compared to vehicle-treated mice. In addition to this interesting antimalarial activity, it showed moderate antitrypanosomal activity but no activity in an acute model. It was also inactive on promastigotes. This highlights its selective antimalarial efficacy and leads to further investigation to assess its potential as new antimalarial lead compound.

The antimalarial activity of indole alkaloids and hybrids

“…[45] Moreover, these two bisindole alkaloids (CC 50 pressed the parasitaemia by 60% on Day 7 compared with vehicletreated mice) in a P. berghei murine model. [46][47][48] Moreover, no acute toxicity was observed at the dose of 60 mg/kg, implying its excellent safety profile.…”

“…Strychnogucine B ( 14 ), a bisindole alkaloid previously isolated from Strychnos icaja , not only showed strong in vitro antiplasmodial activity against FCA 20, FCB1‐R, and W2 strain of P. falciparum with IC 50 values of 85–617 nM, but also demonstrated promising in vivo potency (30 mg·kg −1 ·day −1 , intraperitoneally administrated, suppressed the parasitaemia by 60% on Day 7 compared with vehicle‐treated mice) in a P. berghei murine model. [ 46–48 ] Moreover, no acute toxicity was observed at the dose of 60 mg/kg, implying its excellent safety profile.…”

Antioxidant and Ethnobotanical Study of Strychnos icaja Baillon (Loganiaceae) from Gabon

“…Lusakibanza M et al [13] have also shown that the methanolic and dichloromethane extracts of the root bark had a very good selectivity index on falciparum strains. In addition to this interesting antimalarial activity, it showed moderate in vitro antitrypanosomal activit [14]. We know that free radicals are responsible for degenerative diseases like Alzheimer and Parkinson's or chronic diseases like diabetes, cancer, inflammatory diseases.…”

In vitro antiviral activity against SARS‐CoV‐2 of 28 Strychnos extracts

“…S. icaja is an African species used as an arrow poison and to treat malaria in Congo, Cameroun and Gabon. Previous studies in our laboratory highlighted the presence of different alkaloids, like isosungucine, strychnogucine B and strychnobaillonine and their antiplasmodial and antimalarial activities (Beaufay et al, 2018;Tchinda et al, 2014). S. mattogrossensis is a South American species growing in the tropical forest of the Amazon.…”

“…Up to date, the therapy of the SARS-CoV-2 is limited to treat the symptoms and not to cure the Covid-19 disease (like Tamiflu for influenza), for this reason, the discovery of new antivirals is crucial.Natural products are an important source of antiviral compounds and therefore are extensively studied (Kim, 2021).Broad studies in our laboratory on Asian, African and Brazilian Strychnos species have been conducted, and have led to the isolation of numerous alkaloidic compounds. These plants have been evaluatedfor their antimalarial and cytotoxic potentials (Beaufay et al, 2018;…”