Design Synthesis And Antitumor Activity Studies Of New Spin-labeled Rotenone And CA-4Derivatives

Cancer (malignant tumors) is a significant health concern nowadays, and which have the second mortality rate only after cardiovascular disease in our country. The Anti-tumor drug, which are in use, is the frequent occurrence of multidrug resistance or have serious side effects. In recent years, there has been a growing interest in the search for anti-tumor drugs with high efficacy, low toxicity and minimum side effects. Chemical modification of a known drug may show exhibiting new properties, which is an advantageous to develop a new anti-tumordrug.Chemical properties and pharmacological activities on stable free radicals has been reported. A large number of studies have shown that stable nitroxides have a broad physiological activity. The compound which stable nitroxides combine with original radicals shown anti-tumor activity. Stable nitroxides can be used as drug carriers to improve the solubility of drugs in oil, then drug accumulation in tumor tissue will rise. Improvement of drug transmembrane transport to target makes activity enhanced and toxicity reduced. The NMR spectra of radicals in solution may, in certain cases, show a single shifted line for each group of equivalent nuclei. We can use electron spin-resonance spectroscopy for online analysis, and thus can study the vivo distribution, pharmacokinetics, and anticancer mechanism of the drug.Rotenone is an odorless chemical used as a broad-spectrum insecticide, piscicide, and pesticide. It occurs naturally in the roots and stems of several plants, such as the jicama vine plant. Rotenone has been used as a pesticide for a long history, however, it possess extensive pharmacological activities besides pesticidal. Now it is use to induce parkinson disease model. Anti-tumor activity of rotenone has been reported but has not been described in depth. In this paper, hydroxyl group were led in by reduction or oximation, then we connected it with stable nitroxide radical by esterification.We detect those derivatives in vitro cytotoxicactivity against four different tumor cell lines, KB (nasopharyngeal), A-549(lung), DU-145(prostate), and KBvin (an MDR KB subline), The results showed that rotenone derivatives3a and3d exhibited more potent cytotoxicity against A-549, DU-145, KB and KBvin compared to rotenone and paclitaxel. More systematic structural modifications will carried out to further clarify these initial interesting findings.Stilbenoids are secondary products of heartwood formation in trees that can act as phytoalexins,which are widely distributed in nature. In chemical terms, they are hydroxylated derivatives of stilbene. There is a growing interest in stilbene derivatives because many activities have been observed. The natural products Combretastatins form Combretaceae are one kind of perspective anti-tumor drugs. Among them, Combretastatin A-4(CA-4) strongly inhibited the polymerization of tubulin bybinding to the chochicine site and showed the most potent cytotoxicity against a variety of human cancer cell lines including multiple drug-resistant cancer cell lines. In this paper, we designed and synthesized stable nitroxide radical spin-labeled CA-4derivatives in vitro cytotoxicactivity against tumor cell lines:KB (nasopharyngeal), A-549(lung), DU-145(prostate), and KBvin (an MDR KB subline), The results showed that CA-4derivatives8h significantly inhibits the growth of four human cancer cell lines.The futher research demonstrated that compound8h interferes with cell proliferation by arresting the cell cycle in a certain phase, induced apoptosis of cells and provide evidence that loss of function of microtubules.