Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used therapeutic agents that exhibit frequent and sometimes severe adverse effects, including gastrointestinal ulcerations and cardiovascular disorders. In an effort to obtain safer NSAIDs, we assessed the direct cyclooxygenase (COX) inhibition activity and we investigated the potential COX binding mode of some previously reported 2-(trimethoxyphenyl)-thiazoles. The in vitro COX inhibition assays were performed against ovine COX-1 and human recombinant COX-2. Molecular docking studies were performed to explain the possible interactions between the inhibitors and both COX isoforms binding pockets. Four of the tested compounds proved to be good inhibitors of both COX isoforms, but only compound A3 showed a good COX-2 selectivity index, similar to meloxicam. The plausible binding mode of compound A3 revealed hydrogen bond interactions with binding site key residues including Arg120, Tyr355, Ser530, Met522 and Trp387, whereas hydrophobic contacts were detected with Leu352, Val349, Leu359, Phe518, Gly526, and Ala527. Computationally predicted pharmacokinetic profile revealed A3 as lead candidate. The present data prove that the investigated compounds inhibit COX and thus confirm the previously reported in vivo anti-inflammatory screening results suggesting that A3 is a suitable candidate for further development as a NSAID.

To facilitate the identification of novel MAO-B inhibitors, we elaborated a consolidated computational approach, including a pharmacophoric atom-based 3D quantitative structure–activity relationship (QSAR) model, activity cliffs, fingerprint, and molecular docking analysis on a dataset of 126 molecules. An AAHR.2 hypothesis with two hydrogen bond acceptors (A), one hydrophobic (H), and one aromatic ring (R) supplied a statistically significant 3D QSAR model reflected by the parameters: R² = 0.900 (training set); Q² = 0.774 and Pearson’s R = 0.884 (test set), stability s = 0.736. Hydrophobic and electron-withdrawing fields portrayed the relationships between structural characteristics and inhibitory activity. The quinolin-2-one scaffold has a key role in selectivity towards MAO-B with an AUC of 0.962, as retrieved by ECFP4 analysis. Two activity cliffs showing meaningful potency variation in the MAO-B chemical space were observed. The docking study revealed interactions with crucial residues TYR:435, TYR:326, CYS:172, and GLN:206 responsible for MAO-B activity. Molecular docking is in consensus with and complementary to pharmacophoric 3D QSAR, ECFP4, and MM-GBSA analysis. The computational scenario provided here will assist chemists in quickly designing and predicting new potent and selective candidates as MAO-B inhibitors for MAO-B-driven diseases. This approach can also be used to identify MAO-B inhibitors from other libraries or screen top molecules for other targets involved in suitable diseases.

The rapid increase of industrial activities leads to serious environmental pollution, especially, in aqueous systems and particularly with heavy metals. Cadmium, one of the most poisonous elements, is rapidly accumulated in the human body, therefore, the efficient removal of cadmium ions from wastewater is an urgent need. Coordination networks (CNs) and its subdivision metal-organic frameworks (MOFs), are structured porous composites which present various special properties. In this work two CNs were used as adsorbent materials for the removal of Cd(II) ions from aqueous solutions. By the reaction of CoSO₄·7H₂O and NiSO₄·7H₂O with N,N-bis(phosphonomethyl)glycine (Gly) in hydrothermal conditions two CNs—Co–Gly and Ni–Gly— were synthesized, respectively. Cadmium adsorption onto the studied CNs was conducted in batch mode, and the effect of pH, initial concentration, contact time, temperature and sorbent weight on the sorption process were investigated. Parametric Method 3 (PM3)semi-empirical analyses of the CNs’ structural properties were performed in order to predict the adsorption properties. For this reason, two octahedral models were calculated and computational predictions were compared with the experimental results. Both computational and experimental adsorption studies found that Ni–Gly presents higher affinity for cadmium ions. Moreover, the adsorbent materials can be readily regenerated and recycled without significant loss of cadmium uptake capacity.

The human immunodeficiency virus type 1 (HIV-1), one of the leading causes of infectious death globally, generates severe damages to people’s immune systems and makes them susceptible to serious diseases. To date, there are no drugs that completely remove HIV from the body. This paper focuses on screening 224,205 natural compounds of ZINC15 NPs subset to identify those with bioactivity similar to non-nucleoside reverse transcriptase inhibitors (NNRTIs) as promising candidates to treat HIV-1. To reach the goal, an in silico approach involving 3D-similarity search, ADMETox, HIV protein-inhibitor prediction, docking, and MM-GBSA free-binding energies was trained. The FDA-approved HIV drugs, efavirenz, etravirine, rilpivirine, and doravirine, were used as queries. The prioritized compounds were subjected to ADMETox, docking, and MM-GBSA studies against HIV-1 reverse transcriptase (RT). Lys101, Tyr181, Tyr188, Trp229, and Tyr318 residues and free-binding energies have proved that ligands can stably bind to HIV-1 RT. Three natural products (ZINC37538901, ZINC38321654, and ZINC67912677) containing oxan and oxolan rings with hydroxyl substituents and one (ZINC2103242) having 3,6,7,8-tetrahydro-2H-pyrido[1,2-a]pyrazine-1,4-dione core exhibited comparable profiles to etravirine and doravirine, with ZINC2103242 being the most promising anti-HIV candidate in terms of drug metabolism and safety profile. These findings may open new avenues to guide the rational design of novel HIV-1 NNRTIs.

The inhibition effect of N,N′-phosphonomethylglycine (PMG) and vinyl phosphonic acid (VPA) on the 3% NaCl acidic solution corrosion of carbon steel iron was studied at different immersion times by potentiodynamic polarization, electrochemical impedance spectroscopy, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, and computational methods. It is found from the polarization studies that PMG and VPA behave as mixed-type inhibitors in NaCl. Values of charge transfer resistance (R_ct) and double layer capacitance (C_dl) in the absence and presence of inhibitors are determined. The PMG and VPA inhibitors were capable of inhibiting the corrosion process up to ≈91% and ≈85%, respectively. In the presence of PMG, the synergic effect of chlorine ions was observed. Density functional theory (DFT) was engaged to establish the adsorption site of PMG, VPA, and their deprotonated states. For studied compounds, the resulted values of E_LUMO, E_HOMO, energy gap (∆E), dipole moment (μ), electronic hardness (η), global softness (σ), electrophilic index (ω), and the electronic potential map are in concordance with the experimental data results regarding their corrosion inhibition behavior and adsorption on the metal surface.