The products of the reaction between 6-amine-1,3-dimethyl uracil and bis-chalcones induce cytotoxicity with massive vacuolation in HeLa cervical cancer cell line.

As a part of our research in the chemistry of chalcones we have prepared four pyrimidine monoadducts of bis-chalcones through the reaction with 6-amino-1,3-dimethyl uracil. These compounds displayed cytotoxicity with a massive vacuolation in different human cell lines in vitro. Compound 6 was the most cytotoxic inducer of vacuoles, this compound induced G1 phase cell cycle arrest, and their cytotoxicity went without morphological and biochemical evidence of apoptotic cell death in HeLa cells. In addition, our results showed that this vacuole formation does not require de novo protein synthesis and the content vacuolar is acidic. Compound 6 induce necrotic cell death with excessive vacuolation, similar to a process of autophagy. Spautin-1 an inhibitor of autophagy, decreased the transformation of microtubule-associated protein 1 light chain 3 (LC3B-I) to LC3B-II and the vacuolation induced by compound 6 in HeLa cells, both autophagy processes. These compounds could be of pivotal importance in the study of non-apoptotic cell death with vacuole formation and could be useful in research into new autophagy inhibitors agents.

Exploring the interplay of physicochemical properties, membrane permeability and giardicidal activity of some benzimidazole derivatives.

This study evaluated the relationship between the physicochemical properties, membrane permeability and in vitro giardicidal activity of twenty nine benzimidazole derivatives (1-7n). The retention time data from reverse phase high performance chromatography (RP-HPLC) were used to estimate aqueous solubility and lipophilicity of these compounds. The apparent permeability was determined using Caco-2 cell monolayer. The calculation of some descriptors, such as Clog P, PSA, was performed using ACD labs software. For benzimidazole derivatives with NHCOOCH(3), CH(3), NH(2), SH and SCH(3) groups at the 2-position, a quadratic type of regression model was obtained with giardicidal activity and aqueous solubility or lipophilicity. On the other hand, giardicidal activity of 2-(trifluoromethyl)-1H-benzimidazole derivatives was influenced by lipophilicity, hydrogen bond donors and molecular volume but it was not determined by their apparent permeability in Caco-2 cell line.