benzofurans and 5-5--6-6--tetrachloro-1-1--3-3--tetraethylbenzimidazolocarbocyanine

To obtain modulators for reducing mitochondrial damage by the inhibition of Aβ oligomer formation, 2-phenylbenzofuran derivatives were designed and prepared. Their inhibitory activity against Aβ fibril formation was screened using ThT fluorescence assay, and the effect of derivatives on mitochondrial function was evaluated using JC-1 and MTT assay. 2-Phenylbenzofuran derivatives with dimethylamino group at p-position had an excellent inhibitory activity against Aβ fibril formation. Particularly, compound 19m alleviated mitochondrial damage remarkably and possessed protective effects against Aβ-induced cytotoxicity.

Topics: Amyloid beta-Peptides; Animals; Benzimidazoles; Benzofurans; Carbocyanines; Cell Line; Cell Survival; Mice; Mitochondria

The lichen compound usnic acid is used for its antimicrobial activities in cosmetic products and is also a component of slimming agents. Its effect against cancer cells was first noted over 30 years ago. In this study possible mechanisms of this effect were investigated using two human cell lines, the breast cancer cell line T-47D and the pancreatic cancer cell line Capan-2. Pure (+)-usnic acid from CLADONIA ARBUSCULA and (-)-usnic acid from ALECTORIA OCHROLEUCA were shown to be equally effective inhibitors of DNA synthesis, with IC (50) 4.2 microg/mL and 4.0 microg/mL for (+) and (-)-usnic acid against T-47D, and 5.3 microg/mL and 5.0 microg/mL against Capan-2, respectively. Flow cytometric analysis confirmed the inhibited entry into the S-phase and showed reduction in cell size. Classical apoptosis, as assessed by TUNEL staining, was not observed. Necrosis, measured by LDH release, was seen only in Capan-2 after exposure for 48 hours. Staining with the mitochondrial dye JC-1 demonstrated dose-dependent loss of mitochondrial membrane potential following treatment with usnic acid in both cell lines. In conclusion, usnic acid had a marked inhibitory effect on growth and proliferation of two different human cancer cell lines and led to loss of mitochondrial membrane potential. Cell survival was little affected; late necrosis was seen in one of the cell lines. No difference was noted between the two enantiomers.

Topics: Antineoplastic Agents, Phytogenic; Benzimidazoles; Benzofurans; Breast Neoplasms; Carbocyanines; Cell Cycle; Cell Line, Tumor; Cell Proliferation; DNA; Dose-Response Relationship, Drug; Female; Flow Cytometry; Humans; Inhibitory Concentration 50; Lichens; Membrane Potential, Mitochondrial; Necrosis; Pancreatic Neoplasms; Phytotherapy; Plant Extracts