Claudio Aquino

Design, synthesis, and cytotoxic evaluation of acyl derivatives of 3-aminonaphtho[2,3-b]thiophene-4,9-dione, a quinone-based system.

A series of 3-acyl derivatives of the dihydronaphtho[2,3-b]thiophen-4,9-dione system were studied with respect to cytotoxicity and topoisomerase II inhibitory activity. These analogues were designed as electron-deficient anthraquinone analogues with potential intercalation ability. Derivatives 3-(diethylamino)-N-(4,9-dioxo-4,9-dihydronaphtho[2,3-b]thiophen-3-yl)propanamide (11m) and 3-(2-(dimethylamino)ethylamino)-N-(4,9-dioxo-4,9-dihydronaphtho[2,3-b]thiophen-3-yl)propanamide (11p) showed a high efficacy in cell lines that were highly resistant to treatment with doxorubicin, such as MDA-MB435 (melanoma), IGROV (ovarian), and SF-295 (glioblastoma) human cell lines. Both compounds inhibit topoisomerase II mediated relaxation of DNA, while only 11p incites arrest at the S phase in Caco-2 cells, inducing a delay of cell cycle progression and an increase of cell differentiation. The ability of these derivatives to modulate small heat shock proteins and cardiotoxicy effects was also explored. In addition, the DNA-binding properties of these compounds were investigated and discussed.

A novel quinone-based derivative (DTNQ-Pro) induces apoptotic death via modulation of heat shock protein expression in Caco-2 cells.

Background and purpose:  The resistance of human colon adenocarcinoma cells to antineoplastic agents may be related to the high endogenous expression of stress proteins, including the family of heat shock proteins (HSPs). Recently, a quinone‐based pentacyclic derivative, DTNQ‐Pro, showed high cytotoxic activity in human colon carcinoma cell lines. The aim of the present study was to determine the precise cellular mechanisms of this cytotoxic action of DTNQ‐Pro.

A New Series of 1,3-Dihidro-Imidazo[1,5-c]thiazole-5,7-Dione Derivatives: Synthesis and Interaction with Aβ(25-35) Amyloid Peptide

Deposition of senile plaques composed of fibrillar aggregates of Aβ‐amyloid peptide is a characteristic hallmark of Alzheimer’s disease. A widely employed approach in the study of anti‐Alzheimer agents involves the identification of substances able to prevent amyloid aggregation, or to disaggregate the amyloid fibrils through a direct structural interaction with the soluble or aggregated forms of the peptide. Here, we report the synthesis of a set of 1,3‐dihydro‐3,6‐disubstituted‐imidazo[1,5‐c]thiazole‐5,7‐dione derivatives supporting different alkyl, aryl and alkylamine side chains. The ability of these compounds to interact with the Aβ(25‐35) peptide was evaluated using circular dichroism, nuclear magnetic resonance and thioflavin fluorescence spectroscopy. A molecular model for Aβ(25‐35)–ligand interactions was calculated by molecular docking procedures. Our data show that the ability of the synthesized compounds to modify the structural behaviour of Aβ(25‐35) varies as a function of the overall structural features of the ligands rather contributions from specific individual substituents.