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...

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Autores principales:	Hani A. Alhadrami, Ahmed M. Sayed, Ahmed O. El-Gendy, Yara I. Shamikh, Yasser Gaber, Walid Bakeer, Noheir H. Sheirf, Eman Z. Attia, Gehan M. Shaban, Basma A. Khalifa, Che J. Ngwa, Gabriele Pradel, Mostafa E. Rateb, Hossam M. Hassan, Dalal H. M. Alkhalifah, Usama Ramadan Abdelmohsen, Wael N. Hozzein
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29b0b93f8e0d4cd3a83720981824c6be
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spelling	oai:doaj.org-article:29b0b93f8e0d4cd3a83720981824c6be2021-12-02T10:44:15ZA metabolomic approach to target antimalarial metabolites in the Artemisia annua fungal endophytes10.1038/s41598-021-82201-82045-2322https://doaj.org/article/29b0b93f8e0d4cd3a83720981824c6be2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82201-8https://doaj.org/toc/2045-2322Abstract 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.Hani A. AlhadramiAhmed M. SayedAhmed O. El-GendyYara I. ShamikhYasser GaberWalid BakeerNoheir H. SheirfEman Z. AttiaGehan M. ShabanBasma A. KhalifaChe J. NgwaGabriele PradelMostafa E. RatebHossam M. HassanDalal H. M. AlkhalifahUsama Ramadan AbdelmohsenWael N. HozzeinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hani A. Alhadrami Ahmed M. Sayed Ahmed O. El-Gendy Yara I. Shamikh Yasser Gaber Walid Bakeer Noheir H. Sheirf Eman Z. Attia Gehan M. Shaban Basma A. Khalifa Che J. Ngwa Gabriele Pradel Mostafa E. Rateb Hossam M. Hassan Dalal H. M. Alkhalifah Usama Ramadan Abdelmohsen Wael N. Hozzein A metabolomic approach to target antimalarial metabolites in the Artemisia annua fungal endophytes
description	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.
format	article
author	Hani A. Alhadrami Ahmed M. Sayed Ahmed O. El-Gendy Yara I. Shamikh Yasser Gaber Walid Bakeer Noheir H. Sheirf Eman Z. Attia Gehan M. Shaban Basma A. Khalifa Che J. Ngwa Gabriele Pradel Mostafa E. Rateb Hossam M. Hassan Dalal H. M. Alkhalifah Usama Ramadan Abdelmohsen Wael N. Hozzein
author_facet	Hani A. Alhadrami Ahmed M. Sayed Ahmed O. El-Gendy Yara I. Shamikh Yasser Gaber Walid Bakeer Noheir H. Sheirf Eman Z. Attia Gehan M. Shaban Basma A. Khalifa Che J. Ngwa Gabriele Pradel Mostafa E. Rateb Hossam M. Hassan Dalal H. M. Alkhalifah Usama Ramadan Abdelmohsen Wael N. Hozzein
author_sort	Hani A. Alhadrami
title	A metabolomic approach to target antimalarial metabolites in the Artemisia annua fungal endophytes
title_short	A metabolomic approach to target antimalarial metabolites in the Artemisia annua fungal endophytes
title_full	A metabolomic approach to target antimalarial metabolites in the Artemisia annua fungal endophytes
title_fullStr	A metabolomic approach to target antimalarial metabolites in the Artemisia annua fungal endophytes
title_full_unstemmed	A metabolomic approach to target antimalarial metabolites in the Artemisia annua fungal endophytes
title_sort	metabolomic approach to target antimalarial metabolites in the artemisia annua fungal endophytes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/29b0b93f8e0d4cd3a83720981824c6be
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A metabolomic approach to target antimalarial metabolites in the Artemisia annua fungal endophytes

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