The Activity Of Saha Derivatives

Cancer is a kind of disease harmful to people’s lives and health in the world. Drug therapy for short chemotherapy is the main treatment. Since there is no clear effect of chemotherapy targets and intense side effects,limited anticancer effects. So efficient and low toxicity of new anticancer drugs is the current research trend.Histone deacetylase inhibitors, a group of targeted anticancer agents, act on histones. The characteristics are high efficiency and low toxicity. SAHA, as histone deacetylase inhibitor, was approved by the US FDA in October 2006 for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. SAHA can be combined directly with HDACs enzyme active site, either directly or indirectly regulate histone acetylation, inducing death by blocking the cell cycle and inducing apoptosis. SAHA has simple structure, high efficiency, wide and low toxicity.So it is necessary for transformation synthesized of a series of SAHA derivatives. Cancer treatment using SAHA derivatives with the ability to inhibit cancer cells would represent a new promising chemotherapeutic strategy. SAHA not only can be used alone, but also in combination with other drugs. So SAHA derivatives come into being.The study determonstrates SAHA derivatives’anticancer activity in human melanoma cell line (A375), human lung cancer cell line (A549) and human gastric cancer cell line (MGC803).We find several compounds B102, B105, B113, B122, B123 and B124 are better than SAHA. They are all potential anticancer drugs, with a good prospect. On basis of these six derivatives for study, I measured SAHA derivatives’anticancer activity in human lung cancer cell lines (H1299,H460) and human hepatoma cell line (HepG2).The anticancer activity of B123 is far higher than SAHA.Thus SAHA derivatives B123 could emerge as an exciting new addition to the cancer therapeutics in the future. Data show that SAHA combination with other chemotherapy drugs have a synergistic effect, therefore, It’s determined IC50 values and CI values (the combined effects of index)on the combination of SAHA derivatives with retinoic acid and cisplatin. The main conclusions are as follows:1, Accomplished the evaluation work of SAHA derivatives in a variety of cell lines on vitro anticancer activity with comparing the activity of SAHA The results indicated the anticancer activity of SAHA derivatives B102, B105, B113, B122, B123 and B124 are better than SAHA. SAHA derivatives exhibited higher anti-proliferative activities better than SAHA in human lung cancer cell lines (H1299,H460) and human hepatoma cell line (HepG2) and determined the effect on apoptosis.2, SAHA derivatives and retinoic acid (all-trans retinoic acid and 13-cis retinoic acid) combination therapy showed high anticancer activities, the inhibition rate was increased after added retinoic acid. SAHA derivatives combined with cisplatin showed lower IC50 values in a certain concentration range. CI<1 means that the two drugs have a synergistic effect. The combination not only improve anticancer effect, but also can reduce the toxicity of chemotherapy drugs.3, The anticancer activity of SAHA derivatives B123 was better than cisplatin. Flow cytometry was used to detecting B123 of inducing death by blocking the cell cycle and inducing apoptosis in lung cancer lines.