The ratios of E/Z isomers of sixteen synthesized 1,3-dihydro-3-(substituted phenylimino)-2H-indol-2-one were studied using experimental and theoretical methodology. Linear solvation energy relationships (LSER) rationalized solvent influence of the solvent-solute interactions on the UV-Vis absorption maxima shifts (ν) of both geometrical isomers using the Kamlet-Taft equation. Linear free energy relationships (LFER) in the form of single substituent parameter equation (SSP) was used to analyze substituent effect on pK, NMR chemical shifts and ν values. Electron charge density was obtained by the use of Quantum Theory of Atoms in Molecules, i.e. Bader's analysis. The substituent and solvent effect on intramolecular charge transfer (ICT) were interpreted with the aid of time-dependent density functional (TD-DFT) method. Additionally, the results of TD-DFT calculations quantified the efficiency of ICT from the calculated charge-transfer distance (D) and amount of transferred charge (Q). The antimicrobial activity was evaluated using broth microdilution method. 3D QSAR modeling was used to demonstrate the influence of substituents effect as well as molecule geometry on antimicrobial activity.

A new Zn(ii)-based complex shows a concentration-dependent apoptotic response in highly resistant pancreatic adenocarcinoma cells with extensive activation of caspase-8 and -9.

A comparative study of antitumor activity of mono-and bis-quinoline based (thio)carbohydrazones was investigated by a series of tests on two human malignant cell lines: acute monocytic leukemia (THP-1) and pancreatic adenocarcinoma cancer stem cells (AsPC-1). Thiocarbohydrazones (TCHs) revealed superior pro-apoptotic activity over carbohydrazones (CHs) on both tested cell phenotypes, also displaying multi-target profile activities. Programmed cell death triggered by TCHs was partially caspasedependent, mainly caspase-8 related. Activity against cancer stem cells (CSCs) was evaluated on 2D monolayers and 3D spheroidal models, where two out of three tested bis-TCHs successfully stimulated apoptosis accompanied by a reduction in size of treated spheres. Additionally, all bis-TCHs induced significant decrease in percentage of CD44-expressing AsPC-1 cells that indicate on their ability to induce reprogramming of CSC phenotype. Current results highly support further assessment of bisTCHs in order to specify their specific targets in cancer cells and particularly in the CSCs subpopulation.

Dynamical properties at the liquid-vapor interface of water are investigated at 298 K on the basis of molecular dynamics simulations and intrinsic surface analysis. Mean surface residence time and diffusion coefficient of the molecules as well as H-bond lifetimes are calculated at the liquid surface, and compared to the bulk values. It is found that surface molecules have a non-negligible diffusion component along the surface normal, although this component is limited in time to 7-15 ps, a value comparable with the mean surface residence time. It is also seen that interfacial molecules move considerably faster, and their H-bonds live shorter than in the bulk liquid phase. This finding is explained by the relation between the number of H-bonded neighbors and mobility, namely that molecules being tethered by more H-bonds move slower, and their H-bonds live longer than in the case of molecules of less extensive H-bonding. Finally, it is found that molecules residing long at the surface are clustering around each other, forming more and longer living H-bonds within the surface layer, but much less outside this layer than other interfacial molecules, indicating that longer surface residence is related to weaker interaction with the subsurface region.3

Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site. Fluorescence quenching at three temperatures (20, 25, and 37°C) was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. The enthalpy and entropy changes upon sulphur-containing compound-HSA interactions were calculated using Van't Hoff equation. Positive values of enthalpy and entropy changes indicate that non-specific, hydrophobic interactions are the main contributors to HSA-compound interaction. Molecular docking and calculated lipophilicity descriptors indicate the same, pointing out that the increased lipophilicity of sulphur-containing compounds might be a reason for their better binding to HSA. Obtained results might contribute to design of novel derivatives with improved pharmacokinetic properties and drug efficacy.