Density Functional Theory, Chemical Reactivity, Pharmacological Potential and Molecular Docking of Dihydrothiouracil-Indenopyridopyrimidines with Human-DNA Topoisomerase II

Abstract

In this work, three computational methods (Hatree-Fock (HF), Møller–Plesset 2 (MP2), and Density Functional Theory (DFT)) using a variety of basis sets are used to determine the atomic and molecular properties of dihydrothiouracil-based indenopyridopyrimidine (TUDHIPP) derivatives. Reactivity descriptors of this system, including chemical potential (µ), chemical hardness (η), electrophilicity (ω), condensed Fukui function and dual descriptors are calculated at B3LYP/6-311++ G (d,p) to identify reactivity changes of these molecules in both gas and aqueous phases. We determined the molecular electrostatic surface potential (MESP) to determine the most active site in these molecules. Molecular docking study of TUDHIPP with topoisomerase II α and β is performed, predicting binding sites and binding energies with amino acids of both proteins. Docking studies of TUDHIPP versus etoposide suggest their potential as antitumor candidates. We have applied Lipinski, Veber’s rules and analysis of the Golden triangle and structure activity/property relationship for a series of TUDHIPP derivatives indicate that the proposed compounds exhibit good oral bioavailability. The comparison of the drug likeness descriptors of TUDHIPP with those of etoposide, which is known to be an antitumor drug, indicates that TUDHIPP can be considered as an antitumor drug. The overall study indicates that TUDHIPP has comparable and even better descriptors than etoposide proposing that it can be as effective antitumor drug, especially 2H, 6H and 7H compounds.

Molecular Structure, Interactions and Antimicrobial Properties of Curcumin-PLGA Complexes – A DFT Study

“…Earlier the molecular selectivity of the site was rst analyzed by Parr and Yang [50] using local reactivity descriptors, in particular, Fukui functions. More recently, Mohamed et al have performed docking studies of Dihydrothiouracil-Indenopyridopyrimidines with Human-DNA Topoisomerase II using theoretical methods [51]. They have determined the electrophilic as well as nucleophilic sites using condensed Fukui functions.…”

Screening of natural compounds from Cyperus rotundus Linn against SARS-CoV-2 main protease (Mpro): An integrated computational approach

“…The criteria followed by this rule include rotatable bonds ≤10 and total number of hydrogen bond donors and acceptors ≤12. A polar surface area limit of less than 140 Å 2 is also a filtering criterion [ [17] , [18] , [19] ]. The compounds that satisfied both the rules, with violation of at most one criterion, were selected for further analysis.…”

Molecular Structure, Spectral Investigations, Hydrogen Bonding Interactions and Reactivity-Property Relationship of Caffeine-Citric Acid Cocrystal by Experimental and DFT Approach

“…The natural bond orbital (NBO) analysis has been performed to study the several charge transfer interactions (lone pair; n → π*, n → σ* and σ → π*) and significant stabilization energies E (2) within the CAF-CA cocrystalline system, which are important parameters to explain the stability of the molecule ( Dunnington and Schmidt, 2012 ). The various properties of CAF, CA and CAF-CA cocrystal have been studied via electronic and chemical reactivity descriptors to predict the parameters like chemical reactivity, stability and site selectivity, which play crucial role in drug designing and its development ( Elshakre et al, 2020 ). The molecular electrostatic potential surface (MESP) ( Perera et al, 2016 ) has been plotted to study the electrophilic, nucleophilic reactivity and interactive behavior of CAF-CA cocrystal as well as of its two constituents CAF and CA.…”