Investigation of nepetolide as a novel lead compound: Antioxidant, antimicrobial, cytotoxic, anticancer, anti-inflammatory, analgesic activities and molecular docking evaluation.

Journal: Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society
Published Date:

Abstract

In the present study, we describe various pharmacological effects and computational analysis of nepetolide, a tricyclic clerodane-type diterpene, isolated from . Nepetolide concentration-dependently (1.0-1000 µg/mL) exhibited 1,1-diphenyl,2-picrylhydrazyl free radical scavenging activity with maximum effect of 87.01 ± 1.85%, indicating its antioxidant potential, as shown by standard drug, ascorbic acid. It was moderately active against bacterial strain of . In brine shrimp's lethality model, nepetolide potently showed cytotoxic effect, with LC value of 8.7 µg/mL. When evaluated for antitumor activity in potato disc tumor assay, nepetolide exerted tumor inhibitory effect of 56.5 ± 1.5% at maximum tested concentration of 1000 µg/mL. Nepetolide at 20 mg/kg reduced carrageenan-induced inflammation (P < .001 vs. saline group) in rat paw. Nepetolide dose-dependently (100-500 mg/kg) decreased acetic acid evoked writhes, as exhibited by diclofenac sodium. investigation of nepetolide was carried out against cyclooxygenase-2, epidermal growth factor receptor and lipoxygenase-2 targets. Virtual screening through Patchdock online docking server identified primarily hydrophobic interactions between ligand nepetolide and receptors proteins. Enhanced hydrogen bonding was predicted with Autodock showing 6-8 hydrogen bonds per target. These results indicate that nepetolide exhibits antioxidant, antibacterial, cytotoxic, anticancer, anti-inflammatory and analgesic activities and should be considered as a lead compound for developing drugs for the remedy of oxidative stress-induced disorders, microbial infections, cancers, inflammations and pain.

Authors

  • Tanzeel Ur Rehman
    Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
  • Arif-Ullah Khan
    Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
  • Azar Abbas
    Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
  • Javid Hussain
    Department of Biological Sciences and Chemistry, University of Nizwa, Nizwa 616, Oman.
  • Farman Ullah Khan
    Department of Chemistry, University of Science and Technology, Bannu, Khyber Pakhtunkhwa, Pakistan.
  • Kimberly Stieglitz
    STEM Biotechnology Division, Roxbury Community College, Roxbury, MA, USA.
  • Shamsher Ali
    College of Professional Studies, Northeastern University, 350 Huntington Avenue, Boston, USA.

Keywords

No keywords available for this article.