Preprint / Version 1

Dual synergistic inhibition of COX and LOX by potential chemicals from Indian daily spices investigated through detailed computational studies

Authors

  • Mithun Rudrapal Department of Pharmaceutical Sciences, School of Biotechnology and Pharmaceutical Sciences, Vignan’s Foundation for Science, Technology & Research (Deemed to Be University), Guntur, 522213 India
  • Wafa Eltayeb Biotechnology Department, Faculty of Science and Technology, Shendi University, Shendi, 414601 Sudan
  • Gourav Rakshit Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Ranchi, 835215 India
  • Amr El-Arabey Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, 11651 Egypt
  • Johra Khan Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al’Majmaah, 11952 Saudi Arabia
  • Sahar Aldosari Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al’Majmaah, 11952 Saudi Arabia
  • Bader Alshehri Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al’Majmaah, 11952 Saudi Arabia
  • Mohnad Abdalla Pediatric Research Institute, Children’s Hospital Affiliated to Shandong University, Jinan, 250022 People’s Republic of China

Keywords:

Subject terms: Computational biology and bioinformatics, Diseases, Health care, Chemistry

Abstract

Cyclooxygenase (COX) and Lipoxygenase (LOX) are essential enzymes for arachidonic acid (AA) to eicosanoids conversion. These AA-derived eicosanoids are essential for initiating immunological responses, causing inflammation, and resolving inflammation. Dual COX/5-LOX inhibitors are believed to be promising novel anti-inflammatory agents. They inhibit the synthesis of prostaglandins (PGs) and leukotrienes (LTs), but have no effect on lipoxin formation. This mechanism of combined inhibition circumvents certain limitations for selective COX-2 inhibitors and spares the gastrointestinal mucosa. Natural products, i.e. spice chemicals and herbs, offer an excellent opportunity for drug discovery. They have proven anti-inflammatory properties. However, the potential of a molecule to be a lead/ drug candidate can be much more enhanced if it has the property of inhibition in a dual mechanism. Synergistic activity is always a better option than the molecule's normal biological activity. Herein, we have explored the dual COX/5-LOX inhibition property of the three major potent phytoconsituents (curcumin, capsaicin, and gingerol) from Indian spices using in silico tools and biophysical techniques in a quest to identify their probable inhibitory role as anti-inflammatory agents. Results revealed the dual COX/5-LOX inhibitory potential of curcumin. Gingerol and capsaicin also revealed favorable results as dual COX/5-LOX inhibitors. Our results are substantiated by target similarity studies, molecular docking, molecular dynamics, energy calculations, DFT, and QSAR studies. In experimental inhibitory (in vitro) studies, curcumin exhibited the best dual inhibitory activities against COX-1/2 and 5-LOX enzymes. Capsaicin and gingerol also showed inhibitory potential against both COX and LOX enzymes. In view of the anti-inflammatory potential these spice chemicals, this research could pave the way for more scientific exploration in this area for drug discovery. Subject terms: Computational biology and bioinformatics, Diseases, Health care, Chemistry

Author Biographies

Johra Khan, Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al’Majmaah, 11952 Saudi Arabia

Health and Basic Sciences Research Center, Majmaah University, Al’Majmaah, 11952 Saudi Arabia

Sahar Aldosari, Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al’Majmaah, 11952 Saudi Arabia

Health and Basic Sciences Research Center, Majmaah University, Al’Majmaah, 11952 Saudi Arabia

Bader Alshehri, Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al’Majmaah, 11952 Saudi Arabia

Health and Basic Sciences Research Center, Majmaah University, Al’Majmaah, 11952 Saudi Arabia