title: Structure-Based Study of Natural Products with Anti-Schistosoma Activity.
abstract: BACKGROUND
  Schistosomiasis is a parasitic protozoal disease caused by flatworms of the genus Schistosoma. Although the disease threatens millions of lives, it is still at the top list of neglected tropical diseases and praziquantel, the only common schistosocidal drug in use, has records of decreasing efficiency and cases of resistance. Also, reports revealed that people in the rural areas, who are most affected, rely mostly on traditional herbal medicines because of limited access to modern healthcare. The use of computers in drug development has become a routine practice because they are cost and time effective.
  
  
  OBJECTIVE
  We used computational techniques to discover potent Schistosoma inhibitors of natural product origin.
  
  
  METHODS
  Computer-based techniques were employed to discover anti-schistosoma lead/hit from plant metabolites isolated from African medicinal plants which have shown activity or are responsible for activity against Schistosomes. The plant metabolites were evaluated for 'drug-likeness' and docked toward four selected validated Schistosoma drug targets; Glutathione S-transferase, Thioredoxin glutathione reductase, Histone deacetylase and Schistosoma masoni arginase, with PDB codes: 1M9A, 2X99, 4BZ8 and 4Q3T respectively.
  
  
  RESULTS
  A total of 27 bioactive compounds with anti-Schistosoma history were retrieved from literature. The phytochemicals with Lipinski violation of ≤ 2 were found to exhibit comparable binding affinities toward the studied targets as the co-crystallized inhibitors. Predicted binding modes of the compounds toward respective target showed key intermolecular interactions involved in the ligandtarget relationship. Moreover, one of the compounds emerged as the most interesting candidate by both being drug-like and inhibiting the activities of the studied enzyme targets at micro-molar range.
  
  
  CONCLUSIONS
  Our study identified schistosocidal leads with high bioavailability profile and the exploration of binding modes could lay the foundation for synthetic modification of the plant metabolites for the development of novel anti-schistosoma drug(s) with new mechanism of action.
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nzukka, Enugu, Nigeria, West Africa.
authors.forename: Ibezim
authors.initials: I
authors.lastname: Akachukwu
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria, West Africa.
authors.forename: Olujide O
authors.initials: OO
authors.lastname: Olubiyi
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nzukka, Enugu, Nigeria, West Africa.
authors.forename: Ata
authors.initials: A
authors.lastname: Kosisochukwu
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nzukka, Enugu, Nigeria, West Africa.
authors.forename: Mbah C
authors.initials: MC
authors.lastname: John
authors.affiliation: Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nzukka, Enugu, Nigeria, West Africa.
authors.forename: Nwodo N
authors.initials: NN
authors.lastname: Justina
mesh_terms: D000818:Animals; D017076:Computer-Aided Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D062105:Molecular Docking Simulation; D064209:Phytochemicals / Q000737:chemistry / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry; D012547:Schistosoma / Q000187:drug effects; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000201:enzymology; D012552:Schistosomiasis / Q000188:drug therapy*; D012556:Schistosomicides / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D064209:Phytochemicals; D012556:Schistosomicides
keywords: Schistosomiasis; docking; molecular dynamics simulation; natural products; virtual screening.