PMID- 35215232
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230308
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 15
IP  - 2
DP  - 2022 Jan 19
TI  - First In Silico Screening of Insect Molecules for Identification of Novel 
      Anti-Parasitic Compounds.
LID - 10.3390/ph15020119 [doi]
LID - 119
AB  - 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.
FAU - Gallinger, Tom L
AU  - Gallinger TL
AUID- ORCID: 0000-0003-3001-481X
AD  - Department of Pharmaceutical Chemistry, Philipps University Marburg, 35032 
      Marburg, Germany.
FAU - Aboagye, Samuel Y
AU  - Aboagye SY
AUID- ORCID: 0000-0001-7702-982X
AD  - Department of Microbial Pathogens and Immunity, Rush University Medical Center, 
      Chicago, IL 60612, USA.
FAU - Obermann, Wiebke
AU  - Obermann W
AD  - Department of Pharmaceutical Chemistry, Philipps University Marburg, 35032 
      Marburg, Germany.
FAU - Weiss, Michael
AU  - Weiss M
AD  - Bioorganic Chemistry, University of Bayreuth, 95440 Bayreuth, Germany.
FAU - Grunweller, Arnold
AU  - Grunweller A
AD  - Department of Pharmaceutical Chemistry, Philipps University Marburg, 35032 
      Marburg, Germany.
FAU - Unverzagt, Carlo
AU  - Unverzagt C
AD  - Bioorganic Chemistry, University of Bayreuth, 95440 Bayreuth, Germany.
FAU - Williams, David L
AU  - Williams DL
AD  - Department of Microbial Pathogens and Immunity, Rush University Medical Center, 
      Chicago, IL 60612, USA.
FAU - Schlitzer, Martin
AU  - Schlitzer M
AD  - Department of Pharmaceutical Chemistry, Philipps University Marburg, 35032 
      Marburg, Germany.
FAU - Haeberlein, Simone
AU  - Haeberlein S
AD  - Institute of Parasitology, Justus Liebig University Giessen, 35392 Giessen, 
      Germany.
LA  - eng
GR  - R33 AI127635/AI/NIAID NIH HHS/United States
GR  - LOEWE Centre DRUID/Hessian Ministry for Science and the Arts/
GR  - AI127635/National Institute of Allergy and Infectious Diseases/
PT  - Journal Article
DEP - 20220119
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC8877563
OTO - NOTNLM
OT  - Schistosoma mansoni
OT  - in silico screening
OT  - insect compounds
OT  - molecular docking
OT  - thioredoxin glutathione reductase
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2022/02/27 06:00
MHDA- 2022/02/27 06:01
PMCR- 2022/01/19
CRDT- 2022/02/26 01:05
PHST- 2021/12/27 00:00 [received]
PHST- 2022/01/16 00:00 [revised]
PHST- 2022/01/17 00:00 [accepted]
PHST- 2022/02/26 01:05 [entrez]
PHST- 2022/02/27 06:00 [pubmed]
PHST- 2022/02/27 06:01 [medline]
PHST- 2022/01/19 00:00 [pmc-release]
AID - ph15020119 [pii]
AID - pharmaceuticals-15-00119 [pii]
AID - 10.3390/ph15020119 [doi]
PST - epublish
SO  - Pharmaceuticals (Basel). 2022 Jan 19;15(2):119. doi: 10.3390/ph15020119.