Dehydration enthalpy and dc conductivity obtained by means of thermogravimetric analysis and complex impedance spectroscopy respectively on three alkaline-earth, i.e. Mg 2+ , Ca 2+ , and Ba 2+ , exchanged montmorillonites with low water loading are reported. These data are compared with those previously reported on the same montmorillonite exchanged with the whole series of alkali cations, i.e. Li + , Na + , K + , Rb + , and Cs + . A comprehensive analysis of the interplay between the interlayer cations and the adsorbed water molecules is thus made possible regarding both the static, i.e. dehydration enthalpy, and dynamics, i.e. dc conductivity, points of view. It is pointed out that dehydration thermodynamics strongly depends on the cation electrostatic potential energy, whereas the dc conductivity temperature behavior, which turns out to be non-Arrhenian for the most hydrated samples can be remarkably well classified using the cation Jones-Dole viscosity B coefficient.

Introduction: Present leishmaniasis treatment regimen has many limitations including severe adverse effects, toxicity, and Leishmania strains resistance. In the present study, the objective is to perform QSAR, molecular docking and ADME prediction studies on benzimidazolylchalcones in order to select an antileishmanial drug candidate.Materials & methods: QSAR models were performed on 12 benzimidazolylchalcones with antileishmanial activities against promastigote strains of L. donovani. Binding free energy calculations were performed using MM-GBSA to assess the affinity of the ligands for the proteins. In addition, the three most active compounds (4a-c, IC50 <1-μM) were docked with the protein phosphodiesterase B1 (PDB ID: 2JK6).Results and Discussion: The optimum model has squared correlation coefficient (R2) of 0.983, and leave-one-out (LOO) cross-validation coefficient (Q2CV) value of 0.942. The number of descriptors involved in the model is acceptable (R2 - Q2CV = 0.041), which confirms the model’s stability and validates the developed model’s predictive power. Docking studies revealed that the best compound 4c formed hydrogen bond with SER 464, pi-cation contact with LYS 61 and hydrophobic interactions with LEU 62, TYR 64 and LEU72 of the active site of L. donovani phosphodiesterase B1. ADME properties results showed that all three molecules have good pharmacokinetic properties.Conclusion: Finally, molecular dynamics simulation studies at 30 ns revealed stable interactions with the 2JK6 protein. This study validates the choice of the ortho-chlorinated derivative of benzimidazolylchalcones as the lead compound for developing new derivatives with optimized antileishmanial properties.

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The present pharmacochemical and modelling work focused on a benzimidazolyl-chalcone series. These previously synthesized compounds were evaluated in vitro for their anticancer activities against a panel of seven human cancer cell lines and normal fibroblasts. Among the new benzimidazole-supported chalcones, nine (9) compounds (compounds 1-4, 6-8 and compounds 10 and 11) showed promising anticancer activities with IC 50 s ranging from 0.83 to 2.58 µM. Compounds 2 and 6 with IC 50 s of 0.83 and 0.86 µM, respectively, were shown to be potent inhibitors of HCT-116 colon cancer cell proliferation. It was therefore necessary, for a development of this new series of chalcones, to establish through a QSAR study, their quantum descriptors according to the DFT calculation method and following the B3LYP/6-31+G (d,p) theory. These descriptive and predictive studies focused on the colon HCT 116 cell line which was found to be more sensitive to the anticancer action of our benzimidazolyl-retrochalcones. QSAR study showed that the electronic energy (E elec), lipophilicity (logP), chemical softness (S) and chemical hardness (η) of benzimidazolyl-retrochalcones play an important role in inhibiting cancer cell proliferation.