Synthesis And Biological Activity Of Chalcone-directed Benzothiazepine Derivatives

Chalcone belong to flavonoids, widely present in licorice, safflower and other plants, chalcone and its derivatives have antiviral, insecticidal, antibacterial activity. My supervisor had synthesized three series of chalcone derivatives which 1,4-Michael reaction products based on the special structure of chalcone. The results of bioassay revealed that the most of compounds exhibited good antiviral bioactivities against plant virus in vivo. At the same time, benzothiazepines compounds with a wide range of biological activity. Thus, chalcone as a lead compound, we designed and synthesized a series containing pyridine benzothiazepine derivatives 3a-3z, and the structures of all compounds were confirmed by the IR, 1H NMR, 13 C NMR and elemental. It's summarized as follows.1. In the synthesis of compound 3a as an example, the synthesis conditions of the target compounds were selected in different solvents, temperature, feed ratio and catalyst. Finally, the optimum reaction conditions were as following: anhydrous acetonitrile/DMF as solvent, K₂CO₃, KI catalyst as catalyst, material mole ratio 1:1.2:2:1?intermediate 2a: 2-chloride-5-chloride methyl pyridine: K₂CO₃: KI?, under refluxing for 5-6 hours.2. The antiviral activity test was carried out by The Half-leaf method, and the results of bioassay showed that most of the target compound to tobacco mosaic virus?TMV? has better curative, protection and inactivation activity at 500 ?g/m L. And the 50% effective concentration(EC₅₀) values of curative activities against TMV of the title compounds were further investigated. Particularly, compounds 3a, 3g, 3i, 3j, 3m, 3q, 3s, 3t, 3v, 3w and 3x possessed appreciable curative bioactivities on TMV, with EC₅₀ were 184.93, 242.88, 194.82, 188.59, 188.09, 220.68, 192.06, 226.29, 203.99, 223.16, 213.27 ?g/m L, respectively; which were superior to that of ningnanmycin?248.80 ?g/m L?.3. The target compounds 3s, 3g, 3m and control drug Ningnanmycin interaction with TMV CP were studied by fluorescence spectroscopy and microscale thermophoresis?MST?. The results showed that, binding of compound 3s and the TMV CP?micromolar? stronger than the control agent Ningnanmycin and 3g, 3m.