Diego R. Merchan Arenas

Selective activity of 2,4-diaryl-1,2,3,4-tetrahydroquinolines on Trypanosoma cruzi epimastigotes and amastigotes expressing β-galactosidase

The growth inhibitory effect on Trypanosoma cruzi epimastigotes and the unspecific cytotoxicity over NCTC-929 fibroblasts of two series of previously synthesized 2,4-diaryl-1,2,3,4-tetrahydroquinolines (THQ), have been studied in vitro and compared with those of benznidazole (BZ). Derivatives AR39, AR40, AR41, AR91 and DM15 achieved outstanding selectivity indexes (SI) on the extracellular form (SITHQ>SIBZ>9.44) and thus, were tested in a more specific in vitro assay against amastigotes, showing less effectiveness than the reference drug (SIBZ>320) but also accomplishing great selectivity on the intracellular stage (SITHQ>25). These promising results, supported by the in silico prediction of high bioavailability and less potential risk than benznidazole, reveal several tetrahydroquinolines as prototypes of potential antichagasic drugs.

Cytotoxic effects of new trans-2,4-diaryl-r-3-methyl-1,2,3,4-tetrahydroquinolines and their interaction with antitumoral drugs gemcitabine and paclitaxel on cellular lines of human breast cancer

Two tetrahydroquinoline compounds, called DM8 and DM12, from a new series of the cis-2,4-diaryl-r-3-methyl-1,2,3,4-tetrahydroquinolines, were selected for cytotoxic effects studies on cellular lines of human breast cancer. The synergistic, additive and antagonistic effects in combination of these compounds with anticancer drugs, such as paclitaxel and gemcitabine, were studied. The isobolograms and their analysis demonstrated models of synergism, additivity and antagonism of these tetrahydroquinolines in the presence of paclitaxel and gemcitabine. Results showed that compounds DM8 and DM12 individually induced growth inhibition on breast cancer cell lines MCF-7 and SKBR3, and the addition of paclitaxel and gemcitabine intensified their cytotoxic activity on both cell lines at conc. below 1 μg/mL. During these studies the compound DM12 was identified as new, perspective and safe agent for adjuvant therapy.

Reacción de imino diels-Alder de tres componentes con precursores de origen natural. Generación de nuevas tetrahidroquinolinas 2, 4-diaril disustituidas

The efficient and diastereoselective synthesis of the new substituted 2,4-diaryl1,2,3,4,-tetrahydroquinoline (THQ) was realized via trans-anethole or cis/transisoeugenol, anilines and benzaldehydes condensation with acid catalysts. The BF3?OEt2 was the most efficient catalyst for this reaction. In addition, the essential oil of anise was employed for the direct synthesis of these compounds (THQ). Finally, the extract of the dry anise seeds was used after the extraction under supercritical fluid conditions (scCO2) and the THQ was obtained in good yield and solventless.