International Journal of Computational and Theoretical Chemistry 2019; 7(1): 6-13 http://www.sciencepublishinggroup.com/j/ijctc doi: 10.11648/j.ijctc.20190701.12 ISSN: 2376-7286 (Print); ISSN: 2376-7308 (Online) In-silico Drug Design, ADMET Screening, MM-GBSA Binding Free Energy of Some Chalcone Substituted 9-Anilinoacridines as HER2 Inhibitors for Breast Cancer Kalirajan Rajagopal * , Pandiselvi Arumugasamy, Gowramma Byran Department of Pharmaceutical Chemistry, JSS College of Pharmacy [A Constituent College of JSS Academy of Higher Education & Research-(Deemed to Be University)], Udhagamandalam, Tamilnadu, India Email address: * Corresponding author To cite this article: Kalirajan Rajagopal, Pandiselvi Arumugasamy, Gowramma Byran. In-silico Drug Design by Docking Studies, ADMET Screening, MM- GBSA Binding Free Energy of Some Chalcone Substituted 9-Anilinoacridines as HER2 Inhibitors Targeting Breast Cancer. International Journal of Computational and Theoretical Chemistry. Vol. 7, No. 1, 2019, pp. 6-13. doi: 10.11648/j.ijctc.20190701.12 Received: January 23, 2019; Accepted: February 25, 2019; Published: March 18, 2019 Abstract: Due to their DNA-intercalating agents 9-aniliinoacridines play an important role as antitumor agents. A Series of some Chalcone substituted 9-aniliinoacridines 1a-x were designed for their anti-breast cancer activity. Molecular docking studies were performed by Glide module of Schrodinger suite-2016, targeted against Human epidermal growth factor receptor HER2 (PDB id-3PP0). In-silico ADMET screening by qikprop module and binding free energy by Prime-MMGBSA module also performed. Based on the binding affinity of the designed molecules with HER2 on the basis of GLIDE score and interaction patterns. Most of the compounds 1a-x have significant Glide scores when compared with standard anticancer drugs ledacrine and tamoxifen. Most of the Chalcone substituted 9-anilinoacridine derivatives 1a-x have good binding affinity with Glide score in the range of -5. 32 to -9.37 compared with the standard ledacrine (-5.23) and tamoxifen (-3.78). The results reveals that, Chalcone substituted 9-amino acridines as HER2 inhibitor and the compounds, 1g, f, b, h, t, u with good Glide score may produce significant anti-breast cancer activity for further refinement. Keywords: Docking Studies, Acridine, Chalcone, MM-GBSA, Antibreast Cancer, HER2 1. Introduction Many chemotherapeutic agents still plays an important role in the fight against cancer. Especially, about 1 in 5 women affected by breast cancer. Human epidermal growth factor receptor HER2 overexpression is present in 20–30% of the breast cancer. HER2 overexpression is associated with a more aggressive disease, higher recurrence rate, and shortened survival [1]. These type of breast cancers, grow and spread more aggressively. The benefit of anti-HER2 therapies are one of the most promising molecules for targeted therapy [2]. Human epidermal growth factor receptor-2 is membrane tyrosine kinase was over expressed and gene amplified in human breast cancers. So it is an important tumor cell proliferation and survival pathways [3]. Breast cancers have up to 25–50 copies of the HER2 gene, and up to 40–100 fold increase in HER2 protein resulting in more than 2 million receptors expressed at the tumor cell surface (ERBB2 amplification in breast cancer analysed by fluorescence in situ hybridization [4]. In general, 9-aminoacridine derivatives are inhibiting DNA due to the ability of acridine nucleus to intercalate into DNA base pair. Presently available 9-aminoacridine derivatives like amsacrine and CI-921 a well-known anti-proliferative agent used in the treatment of acute leukaemia. They are biologically unstable because of the Amsacrine (m-AMSA) and CI-921 possess a methane sulfonyl and a methoxy function at C-1' and C-3' of the 9-anilino ring and readily undergo reversible oxidation either chemically or microsomally converted in to quinonediimine. More than 50% of the dose is excreted as the glutathione conjugate. To address these drawbacks of 9-aminoacridines, the effective strategy is to design some modified drugs to overcome these above problems.