2/3D-QSAR, molecular docking and MD simulation studies of FtsZ protein targeting benzimidazoles derivatives. (February 2019)

• Record Type: Journal Article
• Authors: Ahamad, Shahzaib; Islam, Asimul; Ahmad, Faizan; Dwivedi, Neeraj; Hassan, Md. Imtaiyaz
• Is Part Of: Computational biology and chemistry. Volume 78(2019)
• Page Start: 398
• Page End: 413
• Publication Date: 2019-02
• Subjects: 2/3D-QSAR -- Molecular docking -- MD simulations -- Benzimidazoles -- Mycobacterium tuberculosis; Chemistry -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; Biochemistry -- Data processing; Biology -- Data processing; Molecular biology -- Data processing; Periodicals; Electronic journals; 542.85
• DOI: 10.1016/j.compbiolchem.2018.12.017
• Languages: English
• ISSNs: 1476-9271

Abstract

Abstract: The development of multi-drug and extensively-drug resistant strains of Mycobacterium tuberculosis ( Mtb ) have encouraged to develop new anti-TB agents with a unique mechanism of action. FtsZ, an essential protein of bacterial cytokinesis, has emerged as a validated target for antibacterial therapy. This study describes the utility of benzimidazoles (BI) derivatives as potential FtsZ inhibitors. Through 2/3D QSAR (MLR) molecular modeling, new BI-inhibitors with improved activity have been designed. Statistically significant models from 2D-QSAR (r 2 = 0.90, q 2 = 85 and pred_r 2 = 0.60) indicated that the descriptors such as SaaOcount, –ve Potential Surface Area, and SdsCHE-index modulate the activity of a molecule. Similarly, 3D-QSAR (r 2 = 0.78, q 2 = 0.69 and pred_r 2 = 0.59) results indicated both electrostatic and steric descriptors play a pivotal role. These indications prompted us to design 223 new BI-derivatives, out of which three BI-derivatives (D-83, D-116 andD-223 ) have shown some promising results.