<i>In Silico</i> Comparison of Bioactive Compounds Characterized from <i>Azadirachta indica</i> with an FDA-Approved Drug against Schistosomal Agents: New Insight into Schistosomiasis Treatment
Babatunji Emmanuel Oyinloye,
David Ezekiel Shamaki,
Emmanuel Ayodeji Agbebi,
Sunday Amos Onikanni,
Chukwudi Sunday Ubah,
Raphael Taiwo Aruleba,
Tran Nhat Phong Dao,
Olutunmise Victoria Owolabi,
Olajumoke Tolulope Idowu,
Makhosazana Siduduzile Mathenjwa-Goqo,
Deborah Tolulope Esan,
Basiru Olaitan Ajiboye,
Olaposi Idowu Omotuyi
Affiliations
Babatunji Emmanuel Oyinloye
Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria
David Ezekiel Shamaki
Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria
Emmanuel Ayodeji Agbebi
Institute of Drug Research and Development, S.E. Bogoro Center, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria
Sunday Amos Onikanni
Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria
Chukwudi Sunday Ubah
Department of Epidemiology and Biostatistics, College of Public Health, Temple University, Philadelphia, PA 19121, USA
Raphael Taiwo Aruleba
Department of Physiology, East Carolina University, Greenville, NC 27834, USA
Tran Nhat Phong Dao
Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
Olutunmise Victoria Owolabi
Medical Biochemistry Unit, College of Medicine and Health Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria
Olajumoke Tolulope Idowu
Industrial Chemistry Unit, Department of Chemical Sciences, College of Sciences, Afe Babalola University, Ado-Ekiti 360001, Nigeria
Makhosazana Siduduzile Mathenjwa-Goqo
Biotechnology and Structural Biology (BSB) Group, Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa
Deborah Tolulope Esan
Faculty of Nursing Sciences, College of Health Sciences, Bowen University, Iwo 232102, Nigeria
Basiru Olaitan Ajiboye
Institute of Drug Research and Development, S.E. Bogoro Center, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria
Olaposi Idowu Omotuyi
Institute of Drug Research and Development, S.E. Bogoro Center, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria
The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly difficult to tackle schistosomiasis with praziquantel, a drug known to be effective against all Schistosoma species, due to reports of reduced efficacy and resistance. Therefore, this study seeks to investigate the antischistosomal potential of phytochemicals from Azadirachta indica against proteins that have been implicated as druggable targets for the treatment of schistosomiasis using computational techniques. In this study, sixty-three (63) previously isolated and characterized phytochemicals from A. indica were identified from the literature and retrieved from the PubChem database. In silico screening was conducted to assess the inhibitory potential of these phytochemicals against three receptors (Schistosoma mansoni Thioredoxin glutathione reductase, dihydroorotate dehydrogenase, and Arginase) that may serve as therapeutic targets for schistosomiasis treatment. Molecular docking, ADMET prediction, ligand interaction, MMGBSA, and molecular dynamics simulation of the hit compounds were conducted using the Schrodinger molecular drug discovery suite. The results show that Andrographolide possesses a satisfactory pharmacokinetic profile, does not violate the Lipinski rule of five, binds with favourable affinity with the receptors, and interacts with key amino acids at the active site. Importantly, its interaction with dihydroorotate dehydrogenase, an enzyme responsible for the catalysis of the de novo pyrimidine nucleotide biosynthetic pathway rate-limiting step, shows a glide score and MMGBSA of −10.19 and −45.75 Kcal/mol, respectively. In addition, the MD simulation shows its stability at the active site of the receptor. Overall, this study revealed that Andrographolide from Azadirachta indica could serve as a potential lead compound for the development of an anti-schistosomal drug.
