Bioactivity and cytotoxicity profiling of vincosamide and strictosamide, anthelmintic epimers from Sarcocephalus latifolius (Smith) Bruce leaf

• Published in: Journal of ethnopharmacology 2021-01, Vol.265, p.113142, Article 113142
• Main Authors: Aderibigbe, Segun A., Idowu, Sunday O., Olaniyi, Ajibola A., Wright, Colin W., Fatokun, Amos A.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Anthelmintics; Anthelmintics - isolation & purification; Anthelmintics - pharmacology; Anthelmintics - toxicity; Cytotoxicity; Haemonchus - drug effects; Haemonchus placei; HeLa Cells; Humans; Indole Alkaloids - isolation & purification; Indole Alkaloids - pharmacology; Indole Alkaloids - toxicity; Lethal Dose 50; Mice; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Extracts - toxicity; Plant Leaves; Rubiaceae - chemistry; Sarcocephalus latifolius; Strictosamide; Vinca Alkaloids - isolation & purification; Vinca Alkaloids - pharmacology; Vinca Alkaloids - toxicity; Vincosamide
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2020.113142

The leaf of Sarcocephalus latifolius is known to be used traditionally by the Fulanis in Nigeria to deworm animals. As helminthosis remains a major constraint to profitable livestock production worldwide, a precarious situation aggravated by the advent of resistant parasites, the discovery of new anthelmintics is a priority, necessitating exploration of medicinal plants for their anthelmintic principles. To identify and characterise compounds with anthelmintic activity from the leaf of Sarcocephalus latifolius. Powdered S. latifolius leaves were extracted by successive maceration with n-hexane, chloroform and acetone. The dried extracts were evaluated for anthelmintic activity against Haemonchus placei adult worms, and the most active extract was subjected to bioassay-guided chromatographic separations. The isolated compounds were evaluated for cytotoxicity against the mammalian HeLa and MC3T3-E1 cell lines, using alamar blue and CellTitreGloTM to quantify cell viability. LC50 values were computed from the in vitro anthelmintic activity data by fitting to a non-linear regression equation (variable slope). Isolated compounds were characterized using spectroscopic and mass spectrometric analyses. Anthelmintic activity LC50 values for n-hexane, chloroform and acetone extracts were 47.85, 35.76 and 5.72 (mg/mL), respectively. Chromatographic separation of acetone extract afforded two bioactive epimers, identified as vincosamide (LC50 14.7 mg/mL) and strictosamide (LC50 12.8 mg/mL). Cytotoxicity evaluation showed that, below 200 μg/mL (400 μM), neither compound was toxic to the HeLa or MC3T3-E1 cells. Vincosamide and strictosamide could serve as novel scaffolds for the development of anthelmintic derivatives with improved potency and helminth selectivity. [Display omitted] •Vincosamide and strictosamide were isolated from the leaf of the medicinal plant Sarcocephalus latifolius.•Both compounds exhibited anthelmintic activity, with LC50 values of 14.7 mg/mL and 12.8 mg/mL, respectively.•They were not toxic to cultured HeLa and MC3T3-E1 cells at concentrations below 400μM.•They could serve as prototypes for developing anthelmintic derivatives with improved potency and helminth selectivity.