First In Silico Screening of Insect Molecules for Identification of Novel Anti-Parasitic Compounds

Gallinger, Tom L.; Aboagye, Samuel Y.; Obermann, Wiebke; Weiss, Michael; Grünweller, Arnold; Unverzagt, Carlo; Williams, David L.; Schlitzer, Martin; Haeberlein, Simone

doi:10.3390/ph15020119

Open AccessArticle

First In Silico Screening of Insect Molecules for Identification of Novel Anti-Parasitic Compounds

by

Tom L. Gallinger

¹

,

Samuel Y. Aboagye

²

,

Wiebke Obermann

¹,

Michael Weiss

³,

Arnold Grünweller

¹,

Carlo Unverzagt

³,

David L. Williams

²,

Martin Schlitzer

¹ and

Simone Haeberlein

^4,*

¹

Department of Pharmaceutical Chemistry, Philipps University Marburg, 35032 Marburg, Germany

²

Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL 60612, USA

³

Bioorganic Chemistry, University of Bayreuth, 95440 Bayreuth, Germany

⁴

Institute of Parasitology, Justus Liebig University Giessen, 35392 Giessen, Germany

^*

Author to whom correspondence should be addressed.

Pharmaceuticals 2022, 15(2), 119; https://doi.org/10.3390/ph15020119

Submission received: 27 December 2021 / Revised: 16 January 2022 / Accepted: 17 January 2022 / Published: 19 January 2022

(This article belongs to the Collection Drug Discovery and Development for Tropical Diseases (TDs))

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Abstract

Schistosomiasis is a neglected tropical disease caused by blood flukes of the genus Schistosoma. In silico screenings of compounds for the identification of novel anti-parasitic drug candidates have received considerable attention in recent years, including the screening of natural compounds. For the first time, we investigated molecules from insects, a rather neglected source in drug discovery, in an in silico screening approach to find novel antischistosomal compounds. Based on the Dictionary of Natural Products (DNP), we created a library of 1327 insect compounds suitable for molecular docking. A structure-based virtual screening against the crystal structure of a known druggable target in Schistosoma mansoni, the thioredoxin glutathione reductase (SmTGR), was performed. The top ten compounds predominantly originated from beetles and were predicted to interact particularly with amino acids in the doorstop pocket of SmTGR. For one compound from a jewel beetle, buprestin H, we tested and confirmed antischistosomal activity against adult and juvenile parasites in vitro. At concentrations with anti-parasitic activity, we could also exclude any unspecific cytotoxic activity against human HepG2 cells. This study highlights the potential of insect molecules for the identification of novel antischistosomal compounds. Our library of insect-derived molecules could serve not only as basis for future in silico screenings against additional target proteins of schistosomes, but also of other parasites.

Keywords: Schistosoma mansoni; thioredoxin glutathione reductase; insect compounds; in silico screening; molecular docking

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MDPI and ACS Style

Gallinger, T.L.; Aboagye, S.Y.; Obermann, W.; Weiss, M.; Grünweller, A.; Unverzagt, C.; Williams, D.L.; Schlitzer, M.; Haeberlein, S. First In Silico Screening of Insect Molecules for Identification of Novel Anti-Parasitic Compounds. Pharmaceuticals 2022, 15, 119. https://doi.org/10.3390/ph15020119

AMA Style

Gallinger TL, Aboagye SY, Obermann W, Weiss M, Grünweller A, Unverzagt C, Williams DL, Schlitzer M, Haeberlein S. First In Silico Screening of Insect Molecules for Identification of Novel Anti-Parasitic Compounds. Pharmaceuticals. 2022; 15(2):119. https://doi.org/10.3390/ph15020119

Chicago/Turabian Style

Gallinger, Tom L., Samuel Y. Aboagye, Wiebke Obermann, Michael Weiss, Arnold Grünweller, Carlo Unverzagt, David L. Williams, Martin Schlitzer, and Simone Haeberlein. 2022. "First In Silico Screening of Insect Molecules for Identification of Novel Anti-Parasitic Compounds" Pharmaceuticals 15, no. 2: 119. https://doi.org/10.3390/ph15020119

APA Style

Gallinger, T. L., Aboagye, S. Y., Obermann, W., Weiss, M., Grünweller, A., Unverzagt, C., Williams, D. L., Schlitzer, M., & Haeberlein, S. (2022). First In Silico Screening of Insect Molecules for Identification of Novel Anti-Parasitic Compounds. Pharmaceuticals, 15(2), 119. https://doi.org/10.3390/ph15020119

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First In Silico Screening of Insect Molecules for Identification of Novel Anti-Parasitic Compounds

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