Synthesis of New Styrylquinoline Cellular Dyes, Fluorescent Properties, Cellular Localization and Cytotoxic Behavior

New styrylquinoline derivatives with their photophysical constants are described. The synthesis was achieved via Sonogashira coupling using the newly developed heterogeneous nano-Pd/Cu catalyst system, which provides an efficient synthesis of high purity products. The compounds were tested in preliminary fluorescent microscopy studies to in order to identify their preferable cellular localization, which appeared to be in the lipid cellular organelles. The spectroscopic properties of the compounds were measured and theoretical TD- DFT calculations were performed. A biological analysis of the quinolines that were tested consisted of cytotoxicity assays against normal human fibroblasts and colon adenocarcinoma cells. All of the compounds that were studied appeared to be safe and indifferent to cells in a high concentration range. The presented results suggest that the quinoline compounds that were investigated in this study may be valuable structures for development as fluorescent dyes that could have biological applications

Design and synthesis of anticancer 1-hydroxynaphthalene-2-carboxanilides with a p53 independent mechanism of action

A series of 116 small-molecule 1-hydroxynaphthalene-2-carboxanilides was designed based on the fragment-based approach and was synthesized according to the microwave-assisted protocol. The biological activity of all of the compounds was tested on human colon carcinoma cell lines including a deleted TP53 tumor suppressor gene. The mechanism of activity was studied according to the p53 status in the cell. Several compounds revealed a good to excellent activity that was similar to or better than the standard anticancer drugs. Some of these appeared to be more active against the p53 null cells than their wild-type counterparts. Intercalating the properties of these compounds could be responsible for their mechanism of action

The antimicrobial activity of annona emarginata (Schltdl.) H. Rainer and most active isolated compounds against clinically important bacteria

This research was partially supported by grants from Universidad Nacional de San Luis and PIP 444-CONICET. J.D. thanks a fellowship from CONICET. E.S. and R.M. appreciate National Science Centre grant No 2013/09/B/NZ7/00423. J.K. and J.J. were supported by the grant of the Faculty of Pharmacy of Comenius University in Bratislava No. FaF UK/37/2018 and by SANOFI-AVENTIS Pharma Slovakia, s.r.o. The authors thank Luis A. Del Vitto (UNSL) for his help in the botanical classification and Marcos Maiocchi (UNNE) for the help in the collection of the plant material. B.L., G.E.F. and A.T. thank CICITCA-UNSJ.Annona emarginata (Schltdl.) H. Rainer, commonly known as “arachichú”, “araticú”, “aratigú”, and “yerba mora”, is a plant that grows in Argentina. Infusions and decoctions are used in folk medicine as a gargle against throat pain and for calming toothache; another way to use the plant for these purposes is chewing its leaves. Extracts from bark, flowers, leaves, and fruits from A. emarginata were subjected to antibacterial assays against a panel of Gram (+) and Gram (−) pathogenic bacteria according to Clinical and Laboratory Standards Institute protocols. Extracts from the stem bark and leaves showed moderate activity against the bacteria tested with values between 250–1000 µg/mL. Regarding flower extracts, less polar extracts (hexane, dichloromethane) showed very strong antibacterial activity against methicillin-sensitive Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus ATCC 43300 with values between 16–125 µg/mL. Additionally, hexane extract showed activity against Klebsiella pneumoniae (MIC = 250 µg/mL). The global methanolic extract of the fruits (MeOHGEF) was also active against the three strains mentioned above, with MICs values 250–500 µg/mL. Bioassay-guided fractionation of MeOHGEF led to the isolation of a new main compound—(R)-2-(4-methylcyclohex-3-en-1-yl)propan-2-yl (E)-3-(4-hydroxyphenyl)acrylate (1). The structure and relative configurations have been determined by means of 1D and 2D NMR techniques, including COSY, HMQC, HMBC, and NOESY correlations. Compound 1 showed strong antimicrobial activity against all Gram (+) species tested (MICs = 3.12–6.25 µg/mL). In addition, the synthesis and antibacterial activity of some compounds structurally related to compound 1 (including four new compounds) are reported. A SAR study for these compounds was performed based on the results obtained by using molecular calculations.NC

Structures of the quinoline derivatives.

<p>Structures of the quinoline derivatives.</p

Live cell imaging of the HCT116 cells following treatment with 3a, 3c and 3d using bright field optical microscopy (BF) and fluorescence microscopy (DAPI filter).

<p>Live cell imaging of the HCT116 cells following treatment with 3a, 3c and 3d using bright field optical microscopy (BF) and fluorescence microscopy (DAPI filter).</p

Hydrolysis of compound 3b.

<p>Hydrolysis of compound 3b.</p

UV-VIS absorption (A) and normalized fluorescence (B) spectra of styrylquinolines solutions in DMSO.

<p>UV-VIS absorption (A) and normalized fluorescence (B) spectra of styrylquinolines solutions in DMSO.</p

The comparison of emission spectra of 1a in solvents of various polarity

<p>The comparison of emission spectra of 1a in solvents of various polarity</p

Molecular orbitals of the five quinoline derivatives obtained at the TD-B3LYP/6-31+G(d,p) theory level.

<p>Molecular orbitals of the five quinoline derivatives obtained at the TD-B3LYP/6-31+G(d,p) theory level.</p

Negative orbital (au) of the HOMO (-E_HOMO) and LUMO energies (-E_LUMO), HOMO–LUMO band gap energies that were calculated by PCM//DFT-DFT/B3LYP/6-31+G(d,p) using the PCM model (solvent–DMSO) and the theoretical excited energies (E_g) for dyes.

<p>Negative orbital (au) of the HOMO (-E_HOMO) and LUMO energies (-E_LUMO), HOMO–LUMO band gap energies that were calculated by PCM//DFT-DFT/B3LYP/6-31+G(d,p) using the PCM model (solvent–DMSO) and the theoretical excited energies (E_g) for dyes.</p