A metabolomic approach to target antimalarial metabolites in the Artemisia annua fungal endophytes

Abstract

Fungal endophytes are a major source of anti-infective agents and other medically relevant compounds. However, their classical blinded-chemical investigation is a challenging process due to their highly complex chemical makeup. Thus, utilizing cheminformatics tools such as metabolomics and computer-aided modelling is of great help deal with such complexity and select the most probable bioactive candidates. In the present study, we have explored the fungal endophytes associated with the well-known antimalarial medicinal plant Artemisia annua for their production of further antimalarial agents. Based on the preliminary antimalarial screening of these endophytes and using LC-HRMS-based metabolomics and multivariate analyses, we suggested different potentially active metabolites (compounds 1–8). Further in silico investigation using the neural-network-based prediction software PASS led to the selection of a group of quinone derivatives (compounds 1–5) as the most possible active hits. Subsequent in vitro validation revealed emodin (1) and physcion (2) to be potent antimalarial candidates with IC50 values of 0.9 and 1.9 µM, respectively. Our approach in the present investigation therefore can be applied as a preliminary evaluation step in the natural products drug discovery, which in turn can facilitate the isolation of selected metabolites notably the biologically active ones.

Identification of α-Glucosidase Inhibitors from Leaf Extract of Pepper (Capsicum spp.) through Metabolomic Analysis

“…Hence, OPLS analysis was performed to extract AGI activity-related variations from those that are orthogonal to the response variable The OPLS model exhibited a cumulative R 2 Y and Q 2 value of 0.61 and 0.546, respectively. The observed R 2 and Q 2 values could be taken as fair indicators of the model's adequacy [73]. Moreover, the root means squared error of estimation (RMSEE) at 16.8 and root mean squared error of cross-validation (RMSEcv) at 18.1 exhibited a good fit and prediction capacity of the OPLS model, respectively.…”

The Health Benefits of Emodin, a Natural Anthraquinone Derived from Rhubarb—A Summary Update

“…What is more, emodin has a therapeutic potential for the treatment of ulcerative colitis [22], keratitis [23], cardiac fibrosis [24] and rheumatoid arthritis [25]. According to the most recent research reports, emodin isolated from Artemisia annua has antimalarial properties [26]. In an in vivo study it was demonstrated that emodin acts as an analgesic [27].…”

Anti-Cancer and Anti-Inflammatory Potential of the Green Synthesized Silver Nanoparticles of the Red Sea Sponge Phyllospongia lamellosa Supported by Metabolomics Analysis and Docking Study

“…Accordingly, we subjected the metabolites (1-25) identified in the P. lamellosa-derived extracts (i.e., CE and EE) to the neural networking-based prediction software PASS. This software has shown very good success rate in its predictions, particularly for predictions higher than Pa = 0.5 [27][28][29][30][31][32][33].…”

“…Moreover, they showed a number of hydrophobic interactions with LEU-5, MET-21, HIS-46, TYR-50, and LYS-6 (Figure 6). sPLA2 has been reported to have a crucial role in the growth and development of different types of human cancers (e.g., breast, prostate, liver, and skin), and identified to be a promising target to control these types of tumors [24][25][26][27][28][29][30][31][32][33][34][35].…”

“…It is worth noting that the compounds 1-15 have also shown to be COX inhibitors according to PASS prediction; however, their scoring was poor (Pa < 0.5) (Figure 7). sPLA2 has been reported to have a crucial role in the growth and development of different types of human cancers (e.g., breast, prostate, liver, and skin), and identified to be a promising target to control these types of tumors [22,[24][25][26][27][28][29][30][31][32][33][34].…”