<i>In silico</i> studies on potential MCF-7 inhibitors: a combination of pharmacophore and 3D-QSAR modeling, virtual screening, molecular docking, and pharmacokinetic analysis

<p>Gallic acid and its derivatives exhibit a diverse range of biological applications, including anti-cancer activity. In this work, a data-set of forty-six molecules containing the galloyl moiety, and known to show anticarcinogenic activity against the MCF-7 human cancer cell line, have been chosen for pharmacophore modeling and 3D-Quantitative Structure Activity Relationship (3D-QSAR) studies. A tree-based partitioning algorithm has been used to find common pharmacophore hypotheses. The QSAR model was generated for three, four, and five featured hypotheses with increasing PLS factors and analyzed. Results for five featured hypotheses with three acceptors and two aromatic rings were the best out of all the possible combinations. On analyzing the results, the most robust (<i>R</i>²= .8990) hypothesis with a good predictive power (<i>Q</i>²= .7049) was found to be AAARR.35. A good external validation (<i>R</i>² = .6109) was also obtained. In order to design new MCF-7 inhibitors, the QSAR model was further utilized in pharmacophore-based virtual screening of a large database. The predicted IC₅₀ values of the identified potential MCF-7 inhibitors were found to lie in the micromolar range. Molecular docking into the colchicine domain of tubulin was performed in order to examine one of the probable mechanisms. This revealed various interactions between the ligand and the active site protein residues. The present study is expected to provide an effective guide for methodical development of potent MCF-7 inhibitors.</p

Hierarchical Porous Magnesium Oxide (Hr-MgO) Microspheres for Adsorption of an Organophosphate Pesticide: Kinetics, Isotherm, Thermodynamics, and DFT Studies

In this study, hierarchical porous magnesium oxide (Hr-MgO) microspheres have been fabricated from a hydromagnesite precursor via a facile precipitation method followed by calcination. The Hr-MgO microspheres consist of several nanosheet building blocks that generate a flowerlike architecture. Chlorpyrifos (CPF), a persistent organic pollutant, has been chosen as a model organophosphate pesticide to determine the adsorptive capacities of the fabricated Hr-MgO. The equilibrium adsorption data fits well with the Langmuir isotherm model, showing a maximum adsorption capacity of 3974 mg g^–1, which is the highest value to date. Both kinetic as well as thermodynamic parameters reveal the spontaneous, exothermic, and pseudo-second-order nature of the adsorption process due to chemisorption between the pesticide and the adsorbent. Density functional theory studies suggest the importance of hydroxylation on the MgO surface for the successful destructive adsorption, which takes place via the cleavage of SP and Cl–C bonds resulting in the fragmentation of CPF, which is in good agreement with Fourier transform infrared and mass spectrometric studies. The present study shows the potential use of hierarchically structured porous MgO microspheres as an efficient adsorbent for the removal of CPF pollutant

MOESM1 of Design, synthesis and biological evaluation of antimalarial activity of new derivatives of 2,4,6-s-triazine

Additional file 1. Additional figures

A Chloro-Bridged Heterobimetallic (η⁶‑Arene)ruthenium–Organotin Complex as an Efficient Topoisomerase Iα Inhibitor

The chloro-bridged heterobimetallic complex (η⁶-hexamethylbenzene)­Ru­(dmp)­(μ-Cl)₂Sn­(CH₃)₂Cl₂ was designed, synthesized, and characterized by various spectroscopic methods, viz. IR, ¹H and ¹³C NMR, and ESI MS, and single-crystal X-ray crystallography as an approach toward multitargeting metal-based potential anticancer drug candidates. In vitro DNA binding studies confirmed the binding affinity of the complex toward the minor groove of DNA, which is further validated by docking studies. Furthermore, the complex exhibited significant inhibitory effects on topoisomerase Iα at a very low concentration (∼8 μM). The cytotoxicity of the complex against HeLa and HepG2 cancer cell lines was evaluated, which revealed significant regression in cancerous cells in comparison with the standard drug

A Chloro-Bridged Heterobimetallic (η⁶‑Arene)ruthenium–Organotin Complex as an Efficient Topoisomerase Iα Inhibitor

The chloro-bridged heterobimetallic complex (η⁶-hexamethylbenzene)­Ru­(dmp)­(μ-Cl)₂Sn­(CH₃)₂Cl₂ was designed, synthesized, and characterized by various spectroscopic methods, viz. IR, ¹H and ¹³C NMR, and ESI MS, and single-crystal X-ray crystallography as an approach toward multitargeting metal-based potential anticancer drug candidates. In vitro DNA binding studies confirmed the binding affinity of the complex toward the minor groove of DNA, which is further validated by docking studies. Furthermore, the complex exhibited significant inhibitory effects on topoisomerase Iα at a very low concentration (∼8 μM). The cytotoxicity of the complex against HeLa and HepG2 cancer cell lines was evaluated, which revealed significant regression in cancerous cells in comparison with the standard drug