Molecular Docking studies and in-silico ADMET Screening of Some novel Oxazine substituted 9-Anilinoacridines as Topoisomerase II Inhibitors

Abstract

Introduction:In general, 9-aminoacridine derivatives are inhibiting DNA topoisomerase II (topoII) because of their strong activity due to the ability of acridine nucleus to intercalate into DNA base pair. To get insight of the intermolecular interactions, the molecular docking studies are performed at active site of topoisomerase II. Aim: In this study, an attempt is made for identification of potential ligands from oxazine substituted 9-anilino acridines targeted against topoisomerase-II (1ZXM) using molecular modelling and docking studies by using Schrodinger suit-2012 Maestro 9.3 version. Insilco ADMET screening also performed by qikprop module of Schrodinger suit. Results: The relative binding affinity of the designed compounds towards topoisomerase-II (1ZXM) was selected on the basis of docking score, GLIDE score and interaction patterns. Several compounds showed strong hydrogen bonding interactions with amino acid residues and their hydrophobic interactions and other parameters could also explain their potency to inhibit topoisomerase-II (1ZXM). The oxazine substituted 9-anilino acridine derivatives 1a-1k have good binding affinity with Glide score in the range of -5.7 to -8.06 when compared with the standard ledacrine (-5.24). The ADMET screening of the designed compounds have almost all the properties of the compounds are within the recommended values. Conclusion: Hence, this study provides evidence for consideration of valuable ligands in oxazine substituted 9-anilino acridine derivatives as potential topoisomerase-II inhibitor and further in vitro and in vivo investigations may prove its therapeutic potential

Activity of phytochemical constituents of Curcuma longa (turmeric) and Andrographis paniculata against coronavirus (COVID-19): an in silico approach

“…As part of our ongoing research on searching the potent biological molecules against various diseases by in silico and wet lab methods [34][35][36][37][38][39][40][41][42][43][44], we have designed and evaluated various heterocyclic compounds for their biological activities. Using different modules (Glide, QikProp, and Prime) of Schrödinger suite LLC various computational methods like molecular docking, ADMET screening, and bindingfree energy, calculations were performed to find the interactions responsible for SARS CoV-2 main protease inhibition.…”

Homology Modeling and Virtual Screening Studies of Antigen MLAA-42 Protein: Identification of Novel Drug Candidates against Leukemia—An In Silico Approach

“…Molecular docking protocol is used to predict the preferred orientation of a ligand molecule to the target protein to form a stable complex [40,41]. e docking accuracy is determined by finding how closely the binding confirmation with Computational and Mathematical Methods in Medicine the lowest energy of the cocrystalized ligand molecule predicted by the object scoring function; G-score (Glide score) resembles an experimental binding modes determined by X-ray crystallographic technique [42]. Once the 3D model of MLAA-42 is validated and the target binding pockets are defined, the docking-based virtual screening study is performed using the Glide docking tool incorporated in the Schrödinger package by Maestro [43].…”

<i>In-silico</i> Drug Design, ADMET Screening, MM-GBSA Binding Free Energy of Some Chalcone Substituted 9-Anilinoacridines as HER2 Inhibitors for Breast Cancer

“…Energy minimization of the protein structure was carried out using OPLS3 force field. A grid box was generated to defined the centroid of the active site for docking studies [28]…”

“…The stuctural modification of acridines by the introduction of different substitutions were allowed expansion of research on the structure activity relationship to afford new insight into molecular interactions at the receptor level [20]. Similarly, chalcones are also be an important class of compounds with a wide range of biological activities [21][22][23] like antimicrobial, anticancer etc.…”

“…As part of our ongoing research on searching novel antitumor agents [24][25][26][27], we have designed some novel 9aminoacridine analogues bearing the chalcone residue on 9aminoacridine rings by molecular docking studies by using Schrodinger suit-2016. The results revealed that the newly designed chalcone substituted 9-aniliinoacridines exhibited significant inhibition with HER2 exhibit anti-breast cancer activity.…”