The computational exploration of chemical reactivity and molecular docking of the synthesized formazan compounds (S1‐S6) were studied. Further, their antimicrobial activity against bacterial strains (S. epidermidis, B. cereus, K. pneumoniae and P. aeruginosa) and against fungal strains (T. mentagrophytes, C. albicans, A. niger, S. cerevisiae and C. glabrata) using agar diffusion method and antioxidant activity following DPPH inhibition assays were evaluated. Anticancer activity was executed in vitro model of human breast carcinoma (MCF‐7) cell line. The superior and enhanced antibacterial and antimycotic activities were exhibited by formazan compound (S4) by presenting maximum ZOIs and MICs values. While enhanced antioxidant in terms of percentage inhibition of DPPH and cytotoxic effect on human breast carcinoma‐cells demonstrated by formazan compound (S1) which was further validated by the results of molecular docking studies of (S1) with the human estrogen receptor protein. In order to compute quantum chemical reactivity descriptors from conceptual density functional theory (CDFT) point of view of this system, including chemical potential (μ), chemical hardness (η), electrophilicity (ω), condensed Fukui function and dual descriptors are calculated at the same level of calculation. The most active sites of these molecules are determined and correlated with experimental data. The present investigation displays that formazans compounds could be potential drug candidate that constrains the growth of microbial strains, possess ability to cause cytotoxic effect on carcinoma cells and act as effective scavenger for free radical species.

Computational chemistry, molecular docking, and drug design approaches, combined with the biochemical evaluation of the antitumor activity of selected derivatives of the thiouracil-based dihydroindeno pyrido pyrimidines against topoisomerase I and II. The IC50 of other cell lines including the normal human lung cell line W138, lung cancer cell line, A549, breast cancer cell line, MCF-7, cervical cancer, HeLa, and liver cancer cell line HepG2 was evaluated using biochemical methods. The global reactivity descriptors and physicochemical parameters were computed, showing good agreement with the Lipinski and Veber’s rules of the drug criteria. The molecular docking study of the ligands with the topoisomerase protein provides the binding sites, binding energies, and deactivation constant for the inhibition pocket. Various biochemical methods were used to evaluate the IC50 of the cell lines. The QSAR model was developed for colorectal cell line HCT as a case study. Four QSAR statistical models were predicted between the IC50 of the colorectal cell line HCT to correlate the anticancer activity and the computed physicochemical and quantum chemical global reactivity descriptors. The predictive power of the models indicates a good correlation between the observed and the predicted activity.

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.

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