Antiplasmodial and antileishmanial flavonoids from Mundulea sericea

Carolyne Chepkirui,Purity J Ochieng,Biswajyoti Sarkar,Aabid Hussain,Chiranjib Pal,Li Jun Yang,Paolo Coghi,Hoseah M Akala,Solomon Derese,Albert Ndakala,Matthias Heydenreich,Vincent K.W Wong,Máté Erdélyi,Abiy Yenesew

doi:10.1016/j.fitote.2020.104796

Abstract

Five known compounds (1–5) were isolated from the extract of Mundulea sericea leaves. Similar investigation of the roots of this plant afforded an additional three known compounds (6–8). The structures were elucidated using NMR spectroscopic and mass spectrometric analyses. The absolute configuration of 1 was established using ECD spectroscopy. In an antiplasmodial activity assay, compound 1 showed good activity with an IC50 of 2.0 μM against chloroquine-resistant W2, and 6.6 μM against the chloroquine-sensitive 3D7 strains of Plasmodium falciparum. Some of the compounds were also tested for antileishmanial activity. Dehydrolupinifolinol (2) and sericetin (5) were active against drug-sensitive Leishmania donovani (MHOM/IN/83/AG83) with IC50 values of 9.0 and 5.0 μM, respectively. In a cytotoxicity assay, lupinifolin (3) showed significant activity on BEAS-2B (IC50 4.9 μM) and HePG2 (IC50 10.8 μM) human cell lines. All the other compounds showed low cytotoxicity (IC50 > 30 μM) against human lung adenocarcinoma cells (A549), human liver cancer cells (HepG2), lung/bronchus cells (epithelial virus transformed) (BEAS-2B) and immortal human hepatocytes (LO2)

Highlights

Protozoan infections are responsible for serious human diseases, such as amoebiasis, Chaga’s disease, malaria, African sleeping sickness, leishmaniosis, and toxoplasmosis [1] that cause more than a million deaths annually [2]
In 2018, more than 95% of new visceral leishmaniasis occurred in Brazil, China, Ethiopia, India, Iraq, Kenya, Nepal, Somalia, South Sudan and Sudan, with an estimated 85% of new cutaneous leishmaniosis cases added from Afghanistan, Algeria, Bolivia, Brazil, Colombia, Iran, Iraq, Pakistan, the Syrian Arab Republic and Tunisia
We report the isolation and characterization of a new flavonoid along with seven known compounds from the leaves and roots of Mundulea sericea

Summary

Introduction

Protozoan infections are responsible for serious human diseases, such as amoebiasis, Chaga’s disease, malaria, African sleeping sickness, leishmaniosis, and toxoplasmosis [1] that cause more than a million deaths annually [2]. The protozoan parasites that cause these diseases live in human blood or tissue, and are transmitted via blood probing insect vectors, mosquitoes or sand flies [3]. These diseases constitute the major health challenges for sub-Saharan countries including Kenya and Indian subcontinents [4,5,6]. In 2018, more than 95% of new visceral leishmaniasis occurred in Brazil, China, Ethiopia, India, Iraq, Kenya, Nepal, Somalia, South Sudan and Sudan, with an estimated 85% of new cutaneous leishmaniosis cases added from Afghanistan, Algeria, Bolivia, Brazil, Colombia, Iran, Iraq, Pakistan, the Syrian Arab Republic and Tunisia. Due to the development of resistance to current drugs [5,7,8], there is an urgent need to find alternative leads to fight malaria and leishmaniasis

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