In vitro antiplasmodial, molecular docking and pharmacokinetics studies of specialized metabolites from Tetrapleura tetraptera (Fabaceae)

• Published in: South African journal of botany 2022-12, Vol.151, p.949-959
• Main Authors: Sikam, Klev Gaïtan, Happi, Gervais Mouthé, Ahmed, Sikiru Akinyeye, Wakeu, Brussine Nadege Kweka, Meikeu, Livine Zemo, Salau, Shina, Wansi, Jean Duplex
• Format: Article
• Language: English
• Subjects: ADMET study; Fabaceae; Molecular docking; Plasmodium falciparum; Tetrapleura tetraptera
• ISSN: 0254-6299; 1727-9321
• DOI: 10.1016/j.sajb.2022.11.021

Tetrapleura tetraptera is a well-known plant widely used in Cameroon as spices in cooking and in preparations prescribed in folk medicine for the treatment of malaria. The main purpose of this study was to provide relevant chemical and pharmacological insights that can support the effectiveness of T. tetraptera against malaria by identifying the lead compounds that may be responsible for its therapeutic potential. The stem bark and root methanolic crude extracts of this plant displayed a good inhibition of P. falciparum 3D7 with rates of 83.6% and 76.3%, respectively. A total of sixteen distinct compounds (1‒16) have been isolated during the chemical investigations of the two active crude extracts. Their structures were established with the aid of their NMR data. Thriteen compounds (2‒9, 11‒13, 15 and 16) were screened for antiplasmodial activity using P. falciparum 3D7. Results showed that seven tested compounds displayed good activity (IC50< 7 μM) and the most effective were compounds 5, 9, 7, 2 and 6 with IC50 values of (1.8 ± 0.4 μM), (1.9 ± 0.8 μM), (2.1 ± 0.5 μM), (2.3 ± 0.7 μM), (2.4 ± 0.6 μM), respectively. The in silico evaluation of the isolated compounds for their ability to inhibit the P. falciparum dihydroorotate dehydrogenase 5TBO and their ADMET studies revealed that up to fifteen isolated compounds displayed a greater affinity to the binding site of the 5TBO receptor compared to the reference drug chloroquine. More especially, compounds 1, 2, 4, 8 and 14 demonstrated a good drug-likeness. These findings support the use of T. tetraptera for the management of malaria and further qualify it as an important source of good candidates in new antiplasmodial drug development. [Display omitted] •Bioguided fractionation of the active extracts of Tetrapleura tetraptera led to isolation of sixteen compounds.•The crude extracts and thirteen compounds have been evaluated for their antiplasmodial activity against Plasmodium falciparum 3D7 strain.•Six compounds displayed good antiplasmodial activity with IC50 ranging from 1.9 μM to 4.4 μM.•The action mechanism of the more potent compounds, their molecular docking and ADMET study are presented.•The obtained results further support the use of T. tetraptera for the cure of malaria in traditional medicine.