<i>In Silico</i> Computational Studies of Bioactive Secondary Metabolites from <i>Wedelia trilobata</i> against Anti-Apoptotic B-Cell Lymphoma-2 (Bcl-2) Protein Associated with Cancer Cell Survival and Resistance
Hittanahallikoppal Gajendramurthy Gowtham,
Faiyaz Ahmed,
Satish Anandan,
C. S. Shivakumara,
Ashween Bilagi,
Sushma Pradeep,
Chandan Shivamallu,
Ali A. Shati,
Mohammad Y. Alfaifi,
Serag Eldin I. Elbehairi,
Raghu Ram Achar,
Ekaterina Silina,
Victor Stupin,
Mahadevamurthy Murali,
Shiva Prasad Kollur
Affiliations
Hittanahallikoppal Gajendramurthy Gowtham
Department of PG Studies in Biotechnology, Nrupathunga University, Nrupathunga Road, Bangalore 560001, India
Faiyaz Ahmed
Department of Clinical Nutrition, College of Applied Health Sciences in Ar Rass, Qassim University, Al Qassim Region, Ar Rass 51921, Saudi Arabia
Satish Anandan
Department of Clinical Nutrition and Dietetics, Sri Devaraj Urs Academy of Higher Education and Research, Kolar 563103, Karnataka, India
C. S. Shivakumara
Department of Clinical Nutrition and Dietetics, Sri Devaraj Urs Academy of Higher Education and Research, Kolar 563103, Karnataka, India
Ashween Bilagi
Department of Integrative Medicine, Sri Devaraj Urs Academy of Higher Education and Research, Kolar 563103, Karnataka, India
Sushma Pradeep
Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, India
Chandan Shivamallu
Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, India
Ali A. Shati
Biology Department, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia
Mohammad Y. Alfaifi
Biology Department, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia
Serag Eldin I. Elbehairi
Biology Department, Faculty of Science, King Khalid University, Abha 9004, Saudi Arabia
Raghu Ram Achar
Division of Biochemistry, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru 570015, India
Ekaterina Silina
Institute of Biodesign and Modeling of Complex Systems, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia
Victor Stupin
Department of Hospital Surgery, N.I. Pirogov Russian National Research Medical University, 117997 Moscow, Russia
Mahadevamurthy Murali
Department of Studies in Botany, University of Mysore, Manasagangotri, Mysuru 570006, Karnataka, India
Shiva Prasad Kollur
School of Physical Sciences, Amrita Vishwa Vidyapeetham, Mysuru Campus, Mysuru 570026, Karnataka, India
In the present study, the binding affinity of 52 bioactive secondary metabolites from Wedelia trilobata towards the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein (PDB: 2W3L) structure was identified by using in silico molecular docking and molecular dynamics simulation. The molecular docking results demonstrated that the binding energies of docked compounds with Bcl-2 protein ranged from −5.3 kcal/mol to −10.1 kcal/mol. However, the lowest binding energy (−10.1 kcal/mol) was offered by Friedelin against Bcl-2 protein when compared to other metabolites and the standard drug Obatoclax (−8.4 kcal/mol). The molecular dynamics simulations revealed that the Friedelin-Bcl-2 protein complex was found to be stable throughout the simulation period of 100 ns. Overall, the predicted Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of Friedelin are relatively better than Obatoclax, with the most noticeable differences in many parameters where Friedelin has no AMES toxicity, hepatotoxicity, and skin sensitization. The ADMET profiling of selected compounds supported their in silico drug-likeness properties. Based on the computational analyses, the present study concluded that Friedelin of W. trilobata was found to be the potential inhibitor of the Bcl-2 protein, which merits attention for further in vitro and in vivo studies before clinical trials.
