Designing of phenol-based beta-carbonic anhydrase1 inhibitors through QSAR, molecular docking, and MD simulation approach

作者：Ahamad Shahzaib; Hassan Md Imtaiyaz; Dwivedi Neeraja^*

来源：3 Biotech, 2018, 8(5): 256.

DOI：10.1007/s13205-018-1278-z

• beta-Carbonic anhydrase 1
• Docking
• QSAR
• MD simulation
• M. Tuberculosis

Tuberculosis (Tb) is an airborne infectious disease caused by Mycobacterium tuberculosis. Beta-carbonic anhydrase 1 (beta-CA1) has emerged as one of the potential targets for new antitubercular drug development. In this work, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular docking, and molecular dynamics (MD) simulation approaches were performed on a series of natural and synthetic phenol-based beta-CA1 inhibitors. The developed 3D-QSAR model (r(2) =0.94, q(2) =0.86, and pred_r(2) = 0.74) indicated that the steric and electrostatic factors are important parameters to modulate the bioactivity of phenolic compounds. Based on this indication, we designed 72 new phenolic inhibitors, out of which two compounds (D25 and D50) effectively stabilized beta-CA1 receptor and, thus, are potential candidates for new generation antitubercular drug discovery program.

• 出版日期2018-5-14