Mechanistic inhibition of gastric cancer-associated bacteria Helicobacter pylori by selected phytocompounds: A new cutting-edge computational approach
Shopnil Akash,
Imren Bayıl,
Sajjat Mahmood,
Nobendu Mukerjee,
Tamanna Akter Mili,
Kuldeep Dhama,
Md Anisur Rahman,
Swastika Maitra,
Mohamed Mohany,
Salim S. Al-Rejaie,
Nemat Ali,
Prabhakar Semwal,
Rohit Sharma
Affiliations
Shopnil Akash
Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Birulia, 1216, Ashulia, Dhaka, Bangladesh; Corresponding author.
Imren Bayıl
Department of Bioinformatics and Computational Biology, Gaziantep University, Turkey
Sajjat Mahmood
Department of Microbiology, Jagannath University, Chittaranjan Avenue in Sadarghat, Dhaka, 1100, Bangladesh
Nobendu Mukerjee
Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute Of Medical and Technical Sciences, Chennai, India; Department of Microbiology, West Bengal State University, West Bengal, Kolkata, 700126, India; Department of Health Sciences, Novel Global Community Educational Foundation, Hebersham, NSW, Australia
Tamanna Akter Mili
Department of Pharmacy, University of Asia Pacific, 74/A Green Rd, Dhaka, 1205, Bangladesh
Kuldeep Dhama
Division of Pathology, ICAR-Indian Veterinary Research Institute (IVRI), Izatnagar, 243122, Bareilly, Uttar Pradesh, India
Md Anisur Rahman
Department of Pharmacy, Islamic University, Kushtia, Bangladesh
Swastika Maitra
Department of Microbiology, Adamas University, West Bengal, Kolkata, 700126, India
Mohamed Mohany
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh, 1145, Saudi Arabia
Salim S. Al-Rejaie
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh, 1145, Saudi Arabia
Nemat Ali
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh, 1145, Saudi Arabia
Prabhakar Semwal
Department of Biotechnology, Graphic Era University, Dehradun, Uttarakhand, 248002, India
Rohit Sharma
Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Science, Banaras Hindu University, Varanasi, 221005, India; Corresponding author.
Background: Helicobacter pylori (H. pylori) is a persistent bacterial inhabitant in the stomachs of approximately half the global populace. This bacterium is directly linked to chronic gastritis, leading to a heightened risk of duodenal and gastric ulcer diseases, and is the predominant risk factor for gastric cancer - the second most common cause of cancer-related deaths globally. The increasing prevalence of antibiotic resistance necessitates the exploration of innovative treatment alternatives to mitigate the H. pylori menace. Methods: Initiating our study, we curated a list of thirty phytochemicals based on previous literature and subjected them to molecular docking studies. Subsequently, eight phytocompounds—Glabridin, Isoliquiritin, Sanguinarine, Liquiritin, Glycyrrhetic acid, Beta-carotin, Diosgenin, and Sarsasapogenin—were meticulously chosen based on superior binding scores. These were further subjected to an extensive computational analysis encompassing ADMET profiling, drug-likeness evaluation, principal component analysis (PCA), and molecular dynamic simulations (MDs) in comparison with the conventional drug, Mitomycin. Results: The natural compounds investigated demonstrated superior docking affinities to H. pylori targets compared to the standard Mitomycin. Notably, the phytocompounds Diosgenin and Sarsasapogenin stood out due to their exceptional binding affinities and pharmacokinetic properties, including favorable ADMET profiles. Conclusion: Our comprehensive and technologically-advanced approach showcases the potential of identified phytocompounds as pioneering therapeutic agents against H. pylori-induced gastric malignancies. In light of our promising in silico results, we recommend these natural compounds as potential candidates for advancing H. pylori-targeted drug development. Given their potential, we strongly advocate for subsequent in vitro and in vivo studies to validate their therapeutic efficacy against this formidable gastrointestinal bacterium.
