Modelling the structural and reactivity landscapes of tucatinib with special reference to its wavefunction-dependent pro
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ORIGINAL PAPER
Modelling the structural and reactivity landscapes of tucatinib with special reference to its wavefunction-dependent properties and screening for potential antiviral activity Ali Alsalme 1 & T. Pooventhiran 2 & Nabil Al-Zaqri 1 & D. Jagadeeswara Rao 3 & Siriki Srinivasa Rao 4 & Renjith Thomas 2 Received: 26 August 2020 / Accepted: 8 November 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract HER-2 type breast cancer is one of the most aggressive malignancies found in women. Tucatinib is recently developed and approved as a potential medicine to fight this disease. In this manuscript, we present the gross structural features of this compound and its reactivity and wave function properties using computational simulations. Density functional theory was used to optimise the ground state geometry of the molecule and molecular docking was used to predict biological activity. As the electrons interact with electromagnetic radiations, electronic excitations between different energy levels are analysed in detail using timedependent density functional theory. Various intermolecular and intermolecular interactions are analysed and reaction sites for attacking electrophiles and nucleophiles identified. Information entropy calculations show that the compound is inherently stable. Docking with COVID-19 proteins show docking score of − 9.42, − 8.93, − 8.45 and − 8.32 kcal/mol respectively indicating high interaction between the drug and proteins. Hence, this is an ideal candidate to study repurposing of existing drugs to combat the pandemic. Keywords DFT . Tucatinib . Docking . NCI . LIE
Introduction Breast cancer is one of the most common type of neoplasm found in women and it is divided basically into different subtypes, viz., Luminal A, Luminal B, HER2-enriched, Basallike and the human epidermal growth factor receptor-2enriched (HER2-E) is indicated by the overexpression of growth factor receptor–related genes and cell cycle–related genes along with low presence of oestrogen-related and basal-related genes [1–3]. Always, there is a risk of metastatic spread to other interorgans like lungs, brain and bone [4, 5]. * Renjith Thomas [email protected] 1
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
2
Department of Chemistry, St. Berchmans College (Autonomous), Changanassery, Kerala, India
3
Department of Physics, Dr. Lankapalli Bullayya College, Visakhapatnam, Andhra Pradesh, India
4
Department of Physics, Mrs. A.V.N.College, Visakhapatnam, Andhra Pradesh, India
HER2 tyrosine kinase inhibitor Lapatinib is widely used for the management of this disease [6]. Tucatinib is recently developed as a promising drug for the management of HER2positive breast cancer [7]. It is also used along with trastuzumab in patients with HER2-positive colorectal cancer [8]. Tucatinib even showed extensive anti-tumour activity and tumour regression in N87 gastric cancer cell line and HER2amplified colorectal, oesophageal and gastric cance
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