Title: Molecular docking studies, in-silico ADMET screening, MM-GBSA binding free energy of some novel chalcone substituted 9-anilinoacridines as topoisomerase II inhibitors

Authors: Rajagopal Kalirajan; K. Iniyavan; G. Rathika; A. Pandiselvi

Addresses: Department of Pharmaceutical Chemistry, JSS College of Pharmacy (JSS Academy of higher Education & Research-Deemed to be university), Udhagamandalam – 643001, Tamilnadu, India ' Department of Chemistry, PSG College of Arts and Science, Coimbatore, Tamilnadu, India ' Department of Chemistry, PSG College of Arts and Science, Coimbatore, Tamilnadu, India ' Department of Pharmaceutical Chemistry, JSS College of Pharmacy (JSS Academy of higher Education & Research-Deemed to be university), Udhagamandalam – 643001, Tamilnadu, India

Abstract: Novel chalcone substituted 9-anilinoacridines(1a-z) were designed by in-silico method for their Topoisomerase-II(Topo-II) inhibitory activity due to DNA-intercalating properties. Docking studies of compounds 1a-z as selective TOPO-II (id-1ZXM) inhibitors by using Schrodinger suit2016-2. Docking study for the molecules were performed by Glide module, in-silico ADMET screening by qikprop module and free binding energy by Prime-MMGBSA module. The binding affinity of molecules towards TOPO-II was selected on the basis of GLIDE score. Many compounds showed strong hydrophobic interactions and hydrogen bonding interactions to inhibit TOPO-II. The compounds 1a-z, except 1k have good binding affinity with Glide scores in the range of -5.52 to -7.27 when compared with the standard Ethacridine(-4.23). The ADMET properties are within the recommended values. MM-GBSA binding results of the most potent inhibitor are favourable. The compounds, 1x,z,m,f,r,i with significant Glide scores may produce significant anti-microbial and anti-cancer activities for further investigations may prove their therapeutic potential.

Keywords: acridine; chalcone; docking studies; in-silico ADMET screening; MM-GBSA; molecular mechanics-generalised born surface area; Topoisomerase II; anti-microbial; anti-cancer.

DOI: 10.1504/IJCBDD.2020.111053

International Journal of Computational Biology and Drug Design, 2020 Vol.13 No.4, pp.347 - 358

Received: 27 Mar 2019
Accepted: 19 Sep 2019
Published online: 06 Nov 2020 *

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