Modelling the structural and reactivity landscapes of tucatinib with special reference to its wavefunction-dependent properties and screening for potential antiviral activity

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 time-dependent 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. Supplementary Information The online version contains supplementary material available at 10.1007/s00894-020-04603-1.

Evaluation of bioactive compounds from Boswellia serrata against SARS-CoV-2

“…In a study, Tucatinib, a drug developed for HER2-positive breast cancer, was repurposed against SARS-CoV-2. The docking results with the Mpro enzyme using PatchDock reported docking score of 5640 and ACE value of − 348.62 (Alsalme et al 2020 ).…”

Facing COVID-19 Via Anti-Inflammatory Mechanism of Action: Molecular Docking and Pharmacokinetic Studies of Six Anti-Inflammatory Compounds Derived from Passiflora edulis

“…Computational chemistry methods and bioinformatics tools are widely used in the field of drug design and for understanding the electronic properties of various drug-molecules [43][44][45][46][47][48]. Physicochemical property is an important parameter of a molecule that influences efficacy, safety or metabolism which could be predicted by using Lipinski's rule of five (RO5) that is: molecular mass < 500; Hydrogen-bond donors (HBD) ≤ 5; Hydrogen-bond acceptors (HBA) < 10; and Log P < 5 [49].…”

Excited-state electronic properties, structural studies, noncovalent interactions, and inhibition of the novel severe acute respiratory syndrome coronavirus 2 proteins in Ripretinib by first-principle simulations

“…The lopinavir, umifenovir, favipiravir, and oseltamivir molecules are also being studied as potentially active drugs against the virus [ 15 ]. Moreover, we have already reported that melatonin is active against this deadly virus [ 16 ] along with tucatinib [ 17 ] and selpercatinib [ 18 ]. Owing to the extensive time that is required to design and develop a drug to treat the virus, it is reasonable to reroute the existing drugs as molecular targets against the virus.…”