Deciphering the enzymatic target of a new family of antischistosomal agents bearing a quinazoline scaffold using complementary computational tools

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Sebastian-Perez V.; García-Rubia A.; Seif el-Din S.H.; Sabra A.-N.A.; El-Lakkany N.M.; William S.; Blundell T.L.; Maes L.; Martinez A.; Campillo N.E.; Botros S.S.; Gil C.

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Publisher: Taylor and Francis Ltd

Publication Date: 15 January 2020

Volume / Issue: Volume 35 / Issue 1

Pages: 511–523

ISSN: 14756366

DOI: 10.1080/14756366.2020.1712595

Scopus: View on Scopus

PubMed: 31939312

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Sebastian-Perez V., Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain; García-Rubia A., Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain; Seif el-Din S.H., Pharmacology Department, Theodor Bilharz Research Institute, Giza, Egypt; Sabra A.-N.A., Pharmacology Department, Theodor Bilharz Research Institute, Giza, Egypt; El-Lakkany N.M., Pharmacology Department, Theodor Bilharz Research Institute, Giza, Egypt; William S., Parasitology Department, Theodor Bilharz Research Institute, Giza, Egypt; Blundell T.L., Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom; Maes L., Laboratory for Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium; Martinez A., Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain; Campillo N.E., Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain; Botros S.S., Pharmacology Department, Theodor Bilharz Research Institute, Giza, Egypt; Gil C., Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain

Abstract

A previous phenotypic screening campaign led to the identification of a quinazoline derivative with promising in vitro activity against Schistosoma mansoni. Follow-up studies of the antischistosomal potential of this candidate are presented here. The in vivo studies in a S. mansoni mouse model show a significant reduction of total worms and a complete disappearance of immature eggs when administered concomitantly with praziquantel in comparison with the administration of praziquantel alone. This fact is of utmost importance because eggs are responsible for the pathology and transmission of the disease. Subsequently, the chemical optimisation of the structure in order to improve the metabolic stability of the parent compound was carried out leading to derivatives with improved drug-like properties. Additionally, the putative target of this new class of antischistosomal compounds was envisaged by using computational tools and the binding mode to the target enzyme, aldose reductase, was proposed. © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Keywords

Drug discovery; quinazoline; Schistosoma mansoni; target deconvolution; Aldehyde Reductase; Animals; Anthelmintics; Dose-Response Relationship, Drug; Enzyme Inhibitors; Male; Mice; Models, Molecular; Molecular Structure; Quinazolines; Structure-Activity Relationship; 1 [4 (trifluoromethyl)benzyl] 6,7 dimethoxy 3 (4 methoxybenzyl)quinazolin 2,4(1h,3h) dione; 1 [4 (trifluoromethyl)benzyl]3 (4 methoxybenzyl)quinazolin2,4(1h,3h) dione; 3 (4 fluorobenzyl) 1 [4 (trifluoromethyl)benzyl] 6,7 dimethoxyquinazolin 2,4(1h,3h) dione; 3 (4 fluorobenzyl) 1 [4 (trifluoromethyl)benzyl]quinazolin 2, 4(1h,3h) dione; 3 benzyl 1 [4 (trifluoromethyl)benzyl]quinazoline 2,4(1h,3h)dione; 6 bromo 1 [4 (trifluoromethyl)benzyl] 3 (4 methoxybenzyl)quinazolin 2,4(1h,3h) dione; 6 bromo 3 (4 fluorobenzyl) 1 [4 (trifluoromethyl)benzyl]quinazolin 2,4(1h,3h) dione; 6 chloro 1 [4 (trifluoromethyl)benzyl] 3 (4 methoxybenzyl)quinazolin 2,4(1h,3h) dione; 6 chloro 3 (4 fluorobenzyl) 1 [4 (trifluoromethyl)benzyl]quinazolin 2,4(1h,3h) dione; 7 bromo 1 [4 (trifluoromethyl)benzyl] 3 (4 methoxybenzyl)quinazolin 2,4(1h,3h) dione; 7 bromo 3 (4 fluorobenzyl) 1 [4 (trifluoromethyl)benzyl]quinazolin 2,4(1h,3h) dione; 8 bromo 1 [4 (trifluoromethyl)benzyl] 3 (4 methoxybenzyl) 6 methylquinazolin 2,4(1h,3h) dione; 8 bromo 3 (4 fluorobenzyl) 1 [4 (trifluoromethyl)benzyl] 6 methylquinazolin 2,4(1h,3h) dione; antischistosomal agent; praziquantel; quinazoline derivative; unclassified drug; anthelmintic agent; enzyme inhibitor; animal experiment; animal model; antiparasitic activity; Article; carbon nuclear magnetic resonance; comparative study; controlled study; crystal structure; drug screening; follow up; human; in vitro study; in vivo study; liver microsome; metabolic stability; microsome; molecular docking; mouse; nonhuman; priority journal; proton nuclear magnetic resonance; animal; chemical structure; chemistry; dose response; drug effect; enzymology; metabolism; molecular model; structure activity relation; synthesis

Citation Information

Scopus Citations: 6

For comprehensive information about the Theodor Bilharz Research Institute (TBRI), its institutional activities, scientific and research achievements, clinical and hospital services, and the diverse expertise offered through its 22 specialized research and clinical departments, as well as opportunities for professional training, specialized workshops, and scientific conferences, readers are invited to visit the Institute’s official website.

The website provides regularly updated information on the Institute’s latest news, research activities, scientific initiatives, clinical services, institutional programs, and academic and professional opportunities.

English Website: https://www.tbri.sci.eg/en/

Arabic Website: https://www.tbri.sci.eg/ar/

Prepared and Uploaded by:

Abdalla F. Abdalla

Electronic Portal Unit

Electronic Portal Unit

Popular Posts

A cost-performance index for nano-optical biosensor evaluation: Systematic evaluation of europium–salicylate luminescent platforms for GPC3-targeted early HCC diagnosis

Image
Bibliographic Information Authors: Hassan Y.M.; El-Tantawi H.; Ali I.R.; Attia M.S. Journal: Talanta Publisher: Elsevier B.V. Publication Date: January 2027 Volume / Issue: Volume 311 Article No.: 130103 ISSN: 399140 DOI: 10.1016/j.talanta.2026.130103 Scopus: View on Scopus PubMed: 42391698 Document Type: Review Authors and Affiliations Hassan Y.M., Department of Zoology, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt; El-Tantawi H., Department of Zoology, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt; Ali I.R., Department of Immunology and Treatment Evaluation, Theodore Bilharz Research Institute, Giza, Egypt; Attia M.S., Chemistry Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi Arabia Abstract Comparative evaluation of nano-optical biosensor platforms lacks a standardised, multi-parameter quantitative framework that integrates analytical performance...
Read more

Interpretation of liver stiffness measurement in patients with mixed liver disease etiologies

Image
Bibliographic Information Authors: El Ray A.; El Ghannam M.; Rautou P.E. Journal: Arab Journal of Gastroenterology Publisher: Elsevier Ltd Publication Date: August 2026 ISSN: 16871979 DOI: 10.1016/j.ajg.2026.05.002 Scopus: View on Scopus PubMed: 42362465 Document Type: Letter Authors and Affiliations El Ray A., Theodor Bilharz Research Institute, Hepatogastroenterology Department, Giza, Egypt, Faculty of Medicine, October 6 University, Egypt; El Ghannam M., Theodor Bilharz Research Institute, Hepatogastroenterology Department, Giza, Egypt; Rautou P.E., Université Paris-Cité, Inserm, Centre de recherche sur l’inflammation, UMR 1149, Paris, France, AP-HP, Hôpital Beaujon, Service d’Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France Abstract Vibration-controlled transient elastography (VCTE)–based liver stiffness measurement (LSM) is widely used for non-invasive assessment of liver fibrosis and p...
Read more

Variable clinical presentations of pulmonary hydatid cysts: a four-case series from a single center in United Arab Emirates, non-endemic region

Image
Bibliographic Information Authors: Yehya M.; Abdallah M.F.H.; Ajeka S.; Al-Masalmeh F.H.; Albaghdadi M.O.J. Journal: Journal of Surgical Case Reports Publisher: Oxford University Press Publication Date: 29 July 2026 Volume / Issue: Volume 2026 / Issue 7 Article No.: rjag658 ISSN: 20428812 DOI: 10.1093/jscr/rjag658 Scopus: View on Scopus Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Yehya M., Department of Thoracic Surgery, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates; Abdallah M.F.H., Department of Radiology, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates, Theodor Bilharz Research Institute, Mahad Al Abhas Al bahari St, Kornish Al Nile, Warraq Al Arab, Al Warak, Governorate, Giza, 3863341, Egypt; Ajeka S., Department of General Surgery, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates; Al-Masalmeh F.H., Department of ...
Read more

Holothuria arenicola Extract-Loaded Polycaprolactone Nanocapsules Attenuate Bile Duct Ligation-Induced Acute Liver Injury

Image
Bibliographic Information Authors: Mansour E.M.; Shemis M.; Fahmy S.R.; Amer M.A.; Mohamed A.S. Journal: Current Nanomedicine Publisher: Bentham Science Publishers Publication Date: September 2026 Volume / Issue: Volume 16 / Issue 5 Pages: 771–786 ISSN: 24681873 DOI: 10.2174/0124681873401484250924125945 Scopus: View on Scopus Document Type: Article Authors and Affiliations Mansour E.M., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt; Shemis M., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt; Fahmy S.R., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt; Amer M.A., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt; Mohamed A.S., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt Abstract Introduction: Cholestatic liver diseases are characterized by jaundice and cholestasis with various conseq...
Read more

Mytilus edulis-mediated green synthesis of selenium nanoparticles with antimicrobial and molluscicidal applications

Image
Bibliographic Information Authors: Dokmak H.-A.A.; AlSedawy M.; Ramadan M.A.; Amin B.H.; Faid A.H.; Abdelmaksoud H.F.; El-Sayed S.M. Journal: Scientific Reports Publisher: Nature Research Publication Date: 7 September 2026 Volume / Issue: Volume 16 / Issue 1 Article No.: 27918 ISSN: 20452322 DOI: 10.1038/s41598-026-65860-3 Scopus: View on Scopus PubMed: 42706305 Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Dokmak H.-A.A., Department of Medical Malacology, Theodor Bilharz Research Institute, Giza, Egypt; AlSedawy M., Microbiology and Immunology Department, Faculty of Pharmacy (For Boys), Al-Azhar University, Cairo, Egypt; Ramadan M.A., Department of Laser Application in Metrology, Photochemistry and Agriculture, National Institute of Laser Enhanced Science (NILES) Cairo University (CU), Giza, Egypt; Amin B.H., The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, 11787,...
Read more

Corrigendum to ‘Eco-friendly approach for the removal and simultaneous detection of cyanide toxins from drinking and wastewater sources’ [Environ. Pollut. 385 (2025) 127094]

Image
Bibliographic Information Authors: El-Sewify I.M.; Shenashen M.A.; Gomaa H.; Selim M.S.; Akhtar N.; Azzam A.; Mekawy M.; Emran M.Y.; Khairy M.; Shahat A.; Hasan M.; Elmarakbi A.; El-Safty S.A. Journal: Environmental Pollution Publisher: Elsevier Ltd Publication Date: September 2026 Volume / Issue: Volume 405 Article No.: 128412 ISSN: 2697491 DOI: 10.1016/j.envpol.2026.128412 Scopus: View on Scopus PubMed: 42259729 Document Type: Erratum Authors and Affiliations El-Sewify I.M., Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1–2-1 Sengen, Ibaraki-ken, Tsukubashi, 305–0047, Japan, Chemistry Department, Faculty of Science, Ain Shams University, Abbasia, Cairo, 11566, Egypt; Shenashen M.A., Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1–2-1 Sengen, Ibaraki-ken, Tsukubashi, 305–0047, Japan; Gomaa H., Research Center for Macromolecules and Biomaterials, Na...
Read more

Multifunctional polycaprolactone-based composite fibers with icariin and glutathione for effective repair of critical-sized bone defects

Image
Bibliographic Information Authors: Yessuf A.M.; Zhang Y.; Sharma B.P.; Wang Y.; Kassa T.S.; Qadir A.; Jinqiu Y.; Mohideen M.M.; Salama A.M.; Wang W.; Zhang Q.; Liu Y. Journal: BMEMat Publisher: John Wiley and Sons Inc Publication Date: 30 July 2026 ISSN: 27517438 DOI: 10.1002/bmm2.70115 Scopus: View on Scopus Document Type: Article Access: All Open Access; Gold Open Access Authors and Affiliations Yessuf A.M., Key Laboratory of Advanced Functional Polymer Composites, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, China; Zhang Y., Henan Provincial Orthopedic Hospital, Henan, Zhengzhou, China; Sharma B.P., Key Laboratory of Electrochemical Process and Technology of Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, China; Wang Y., Beijing University of Chinese Medicine, Beijing, China; Kassa T.S., Key Laboratory of Advanced Functional Polymer Composites, Col...
Read more