Computational Studies of Bioactive Secondary Metabolites from Against Anti-Apoptotic B-Cell Lymphoma-2 (Bcl-2) Protein Associated with Cancer Cell Survival and Resistance

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Feb 25

PMID 36838574

Authors

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

Soon will be listed here.

Abstract

In the present study, the binding affinity of 52 bioactive secondary metabolites from 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 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.

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