Planta Med 2015; 81 - PM_152
DOI: 10.1055/s-0035-1565529

Identification of plasmodial enoyl-ACP reductase inhibitors of Acacia nilotica stem bark and their molecular docking with special reference to DPPH radical scavenging activity

EA Omer 1, A Khalid 2, SA Khalid 1, 3
  • 1Department of Pharmacognosy, Faculty of Pharmacy, University of Khartoum, P.O. Box 1996 Khartoum, Sudan, Khartoum, Sudan
  • 2Medicinal and Aromatic Plants Research Institute, National Center for Research, Sudan, Khartoum, Sudan
  • 3Faculty of Pharmacy, University of Science & Technology, P.O. Box 447, Omdurman, Sudan., Khartoum, Sudan

Plasmodium falciparum is the most serious health threat in Sub-Saharan Africa [1]. Due to the arising resistance, new targets and active compounds are urgently needed. Targeting enoyl-ACP reductase (PfENR), which catalyses the rate limiting step in each elongation cycle in type II fatty acid synthesis pathway, has been validated as an important target [2]. This study aims to discover new antiplasmodial molecules based on PfENR inhibition using in vitro and in silico tools. The study correlates between the antiplasmodial and antioxidant activity of the investigated plant extracts/fractions, to point out molecules which interfere with the redox metabolism of plasmodium.

Selection of the plants studied was based on interviewing traditional healers on the use of locally available antimalarial and/or antipyretic medicinal plants. Accordingly 10 plants were subjected to preliminary screening for their in vitro inhibition of PfENR. Among them five plants were subjected to bioactivity guided fractionation.

The ethyl acetate fraction of Acacia nilotica stem bark revealed a significant PfENR inhibition (IC50 0.87 µg/mL) and reasonable diphenylpicrylhydrazyl scavenging activity (12.5 µg/mL). Therefore, it was further analysed by LC/MS/MS which eventually resulted in the identification of four prominent antiplasmodial compounds. The four compounds and some of their diastereomers were subjected to in silico evaluation by docking against PfENR using SYBYL-X1.1 package and they exhibited a binding affinity of -12.00, -10.66, -9.18, -9.18, -4.7, -5.98 and -9.25 Kcal/mol for (-) catechin, (+) catechin, (+) epicatechin, (-) epicatechin, catechin-7-O-gallate, chrysoeriol and naringenin chalcone, respectively (Fig. 1). Remarkable correlations between the antiplasmodial and antioxidant activity were discerned.

References:

[1] World malaria report 2014

[2] Schrader F.C et al. Novel type II Fatty acid biosynthesis (FAS II) inhibitors as multistage antimalarial agents. Chem Med Chem 2013; 8: 442 – 461