Colchicine-like ß-acetamidoketones as inhibitors of microtubule polymerization: Design, synthesis and biological evaluation of in vitro anticancer activity.

OBJECTIVES: In this study a series of novel colchicine-like ß-acetamidoketones was designed and synthesized as potential tubulin inhibitors. MATERIALS AND METHODS: The cytotoxicity of the novel synthesized ß-acetamidoketones was assessed against two cancerous cell lines including MCF-7 (human breast cancer cells) and A549 (adenocarcinomic human alveolar basal epithelial cells) employing the MTT test. Tubulin polymerization test was done by using a commercial kit (tubulin polymerization assay kit). RESULTS: In general, the cytotoxicity activities were highly dependent on the aromatic substitution pattern of phenyl ring at ß position of ß-acetamidoketones. Based upon, compound 4f possessing the same structural elements of colchicine and chalcone 1, revealed the most cytotoxicity more than the other ß-acetamidoketone against the cancerous cell lines and showed moderate antitubulin effect. The tubulin inhibitory effect of 4f, colchicine and chalcone 1 were consistent with their antiproliferative activities. Molecular docking studies of 4f, into the colchicine-binding site of tubulin exhibited possible mode of interaction between this compound and tubulin. CONCLUSION: The structure activity relationship (SAR) data attained showed that the presence of trimethoxy phenyl attached to carbonyl group of ß-acetamidoketones and a methoxy group at para position of the other ring are essential for cytotoxic activity. In general, the cytotoxicity activities were highly dependent on the aromatic substitution pattern of phenyl ring at ß position of ß-acetamidoketones.

Enhanced Loading and Release of Non-Steroidal Anti-Inflammatory Drugs from Silica-Based Nanoparticle Carriers.

Silica nanoparticles can be potentially considered the carriers of controlled drug systems. In this research, non-steroidal anti-inflammatory drugs were used. Diclofenac sodium and piroxicam were loaded on the considered nanosilica using solvent evaporation method. To prove drug encapsulation on the nanosilica and its rate, infrared spectroscopy, X-ray diffraction, and BET were used, and after proving the existence of the drug in the nanosilica matrix and determining the amount of loading, dissolution test was performed in an environment similar to that of stomach and intestine in terms of pH. Drug loading percentage showed that over 90% of drugs were loaded on nanosilica. Dissolution tests in stomach pH environment showed the control samples (drug without SBA-15) released considerable amount of drugs (about 90%) within first 15 min, when it was about 10-20% for the matrixes. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples. It was indicated nanosilica has the ability of retaining the drugs in acidic pH and prevented their release. Furthermore, the drugs were released in a controlled manner in small intestine, which is the main absorption site.