New hippuric acid derivatives of prospective MDR AcrAB-TolC efflux pump inhibition, isolated from the fossilized metabolic product of Procavia capensis, in vitro supported computational study

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Mohammed M.M.D.; Aljedaie M.M.; Hamed A.A.; Ghareeb M.A.

Journal: Journal of Ethnopharmacology

Publisher: Elsevier Ireland Ltd

Publication Date: June 2026

Volume / Issue: Volume 365

Article No.: 121573

ISSN: 3788741

DOI: 10.1016/j.jep.2026.121573

Scopus: View on Scopus

PubMed: 41903584

Document Type: Article

Authors and Affiliations

Mohammed M.M.D., Pharmacognosy Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Cairo, Dokki, 12622, Egypt; Aljedaie M.M., Department of Biology, College of Science and Humanities, Prince Sattam bin Abdulaziz University, P.O. box 173, Alkharj, 11942, Saudi Arabia; Hamed A.A., Microbial Chemistry Department, National Research Centre, 33 El-Buhouth Street, Dokki, Giza, 12622, Egypt; Ghareeb M.A., Medicinal Chemistry Department, Theodor Bilharz Research Institute, Kornaish El-Nile, Warrak El-Hadar, Imbaba (P.O. 30), Giza, 12411, Egypt

Abstract

Ethnopharmacological relevanceHyraceum, the fossilized excreta of rock hyrax situated in Howtat Bani Tamim, Saudi Arabia, used by tribes' settlers to treat infection associated viruses and bacteria like respiratory, urinary and bladder tracts, as a remedy for epilepsy and hysteria, to treat colic and syphilis, and as a cure for back and abdominal. However, its definitive chemical constituents, biological activity, and pharmacodynamic mechanisms remain uncharacterized.Aim of the studyComprehensive chemical characterization and biological evaluation of the Hyraceum extract in vitro supported by a through in silico computational study.Materials and methodsLC/MS was used to discover the chemical composition of Hyraceum. The -ve and +ve microbial strains like E. coli, P. aeruginosa, S. aureus, C. albicans, were used for antimicrobial and antibiofilm activities. DPPH, PMo, and FCR were used for the antioxidant activity, and the total phenolic content, respectively. Proteins correlated with bactericidal/bacteriostatic effects like IARS, DHPS, Ddl1, DHFR, etc., and AcrAB-TolC efflux pump were selected for the in-silico study. Compounds’ descriptors were estimated using DFT, along with the ADMET prediction.ResultsTwo new hippuric acid derivatives were isolated using RP-HPLC and fully identified using 1D & 2D-NMR, along with, seven phenolic derivatives, eight methoxylated flavonoids, and three sterols were identified using UPLC-ESI-MS/MS. The Hyraceum fractions revealed highest values of 448.71 mg GAE/g (TPC), and 382.59 mg AAE/g (TAC), besides, varied inhibition rations and MICs were displayed against the bacterial and fungal strains with the destruction of the pre-formed biofilms. In-silico modelling demonstrated the multi-target antimicrobial activity of Hyraceum's constituents with prospective MDR AcrB efflux pump inhibition.ConclusionThe Hyraceum composition of the hippuric acids, phenolic acids and/or their derivatives, methoxylated flavonoids and sterols could be accounted for its biological potentials via their ability to interact with the key amino acid residues at the receptors’ active pockets for inhibition, along with, their MDR inhibition activity expressed in targeting AcrB efflux pump transporter. © 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Keywords

Antimicrobial activity; DFT; Hippuric acid; Hyraceum; In silicostudy; Procavia capensis jayakari; UPLC-ESI-MS/MS; Anti-Bacterial Agents; Anti-Infective Agents; Biofilms; Candida albicans; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Molecular Docking Simulation; Pseudomonas aeruginosa; 2',4',6',4 tetrahydroxy 3,5 dimethoxydihydrochalcone; 3 methoxy 4 hydroxyhippuric acid; 4 hydroxyhippuric acid; 5 hydroxy 6,7,8,3',4' pentamethoxyflavone; 5 hydroxy 6,7,8,3',4',5' hexamethoxyflavanone; 5 hydroxy 7,8,3',4',5' pentamethoxyflavanone; 5,6,7,8,3',4' hexamethoxyflavone; 5,7 dimethoxyflavanone; 5,7,4' trihydroxy 3',5' dimethoxyflavone; 5,7,8,4',5' pentamethoxyflavone; antibiotic agent; antioxidant; ascorbic acid; butyl hippurate; cholesterol; ciprofloxacin; flavonoid; fucosterol; glucuronic acid hippuroic acid; hippuric acid derivative; homogentisic acid; Hyraceum extract; nystatin; o methoxyhippuric acid; phenol derivative; Pseudomonas aeruginosa exotoxin A; sitosterol; sterol derivative; unclassified drug; uric acid; antiinfective agent; antibiofilm activity; antioxidant activity; Article; Bacillus subtilis; biological activity; chemical composition; computer model; controlled study; density functional theory; drug absorption; drug distribution; drug excretion; drug isolation; drug metabolism; drug toxicity; Escherichia coli; fossil; hyrax; in vitro study; Klebsiella pneumoniae; liquid chromatography-mass spectrometry; minimum inhibitory concentration; molecular docking; molecular dynamics; nonhuman; prediction; Procavia capensis; prospective study; reversed phase high performance liquid chromatography; Salmonella enterica serovar Typhimurium; Staphylococcus aureus; total antioxidant capacity; ultra performance liquid chromatography; biofilm; chemistry; drug effect; isolation and purification; microbial sensitivity test; multidrug resistance

Citation Information

Scopus Citations: 1

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

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

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

Microbial levan potentiates hepatic retention and antitumor activity of a PEGylated benzimidazole–curcumin nanocomplex through TLR2–FXR/FGF15-associated immunometabolic remodeling in experimental liver cancer

Image
Bibliographic Information Authors: Shawky H.; Ibrahim N.E.; Amer M.N.; Al-Ashmawy A.A.K.; Hammam O.A.; Fayed D.B.; Maghraby A.S. Journal: Scientific Reports Publisher: Nature Research Publication Date: 12 August 2026 Volume / Issue: Volume 16 / Issue 1 Article No.: 25094 ISSN: 20452322 DOI: 10.1038/s41598-026-64576-8 Scopus: View on Scopus PubMed: 42581056 Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Shawky H., Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, 12622, Egypt; Ibrahim N.E., Microbial Biotechnology Department, Biotechnology Research Institute, National Research Centre, Dokki, Cairo, 12622, Egypt; Amer M.N., Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, 12622, Egypt; Al-Ashmawy A.A.K., Therapeutic Chem...
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