| Part1:A novel selective Al3+ fluorescent probe L with high efficiency was design and synthesized based on the rhodamine-B skeleton. With the advantages such as low limit of the detection, good selectivity and capacity of realizing the on-off operation, molecular fluorescent probes attract a lot of attention. Furthermore, the rhodamine-based dyes possess advantages such as low toxicity, the largest emission peaks in infrared-visible spectrum, high quantum yield and perfect water solubility and the rhodamine-based biologically fluorescent probes turn out to become the spotlight in this field.Taking advantage of the condensation of 1-(2-hydroxyphenyl)ethanone and a rhodamine-B derived hydrazide, fluorescent probe L was synthesized and the ultraviolate and fluorescent spectra of L were observed with more than 10 different metal ions. The results revealed that when the Al3+ was added, the ultraviolate absorption and fluorescent emission of L were both enhanced and the solution turned purple from colorless. By condition investigation, we optimized the solution and pH. Through selection investigation, we found out that there was no obvious interference with common metal ions. The limit of the detetion of Al3+ was caculated to be 1.63×10-7 mol/L by the fluorescent titration experiment. Besides, the coordination ration of L and Al3+was proved to be 2:1 by the Job’s plot method and the structure of the complex was confirmed according to the references. Finally, the timeliness and reversibility of L were investigated. Furthermore, this paper successfully applied L for the detection of Al3+ in HeLa cells. Then by MTT method, L revealed no toxicity to living cells, indicating that L could be applied in living organism.Part 2:4-Ethyl-7-(morpholinomethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (11a),4-isopro pyl-7-(morpholinomethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (11b),7-(morpholinome hyl)-4-propyl-2H-benzo[b][1,4]oxazin-3(4H)-one (11c),4-butyl-7-(morpholinomethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (11d),4-benzyl-7-(morpholinomethyl)-2H-benzo [b][1,4]oxazin-3(4H)-one(11e),4-ethyl-7-((4-phenylpiperazin-1-yl)methyl)-2H-benzo [b][1,4]oxazin-3(4H)-one(11f),4-isopropyl-7-((4-phenylpiperazin-1-yl)methyl)-2H benzo[b] [1,4]oxazin-3 (4Hone-4-propyl-7-(2-(4-(2-fluorophenyl) (11g),7-((4-phenyl piperazi-l-yl)methyl)-4-propyl-2Hbenzo[b][1,4]oxazin-3(4H)-one(11h),4-butyl-7-(( 4-phenylpiperazin-1-yl)methyl)-2Hbenzo[b][1,4]oxazin-3(4Hone (11i),4-benzyl-7-((4-phenylpiperazin-1-yl)methyl)-2Hbenzo[b][1,4]oxazin-3(4H)-one(llj),4-ethyl-7-((4-(4-fluorophenyl)piperazin-1-yl)methyl)-2Hbenzo[b][1,4]oxazin-3(4Hone (Ilk), 7-((4-(4-fluorophenyl)piperazin-l-yl)methyl)-4-isopropyl-2H-benzo[b][1,4]oxazin-3(4 H)-one (111),7-((4-(4-fluorophenyl)piperazin-1-yl)methyl)-4-propyl-2Hbenzo[b][1,4] oxazin-3(4H)-one (11m),4-butyl-7-((4-(4-fluorophenyl)piperazin-1-yl)methyl)-2H benzo[b][1,4]oxazin-3(4H)-one (11n),4-benzyl-7-((4-(4-fluorophenyl)piperazin-1-yl) methyl)-2Hbenzo[b][1,4]oxazin-3(4H)-one(11o),4-ethyl-7-((4-(2-fluorophenyl)pipera zin-1-yl)methyl)-2Hbenzo[b][1,4]oxazin-3(4H)-one(11p),7-((4-(2-fluorophenyl)pipe razin-1-yl)methyl)-4-isopropyl-2H-benzo[b][1,4]oxazin-3(4H)-one(11q),7-((4-(2-fluo rophenyl)piperazin-1-yl)methyl)-4-propyl-2H-benzo[b][1,4]oxazin-3(4H)-one(11r), 4-butyl-7-((4-(2-fluorophenyl)piperazin-l-yl)methyl)-2Hbenzo[b][1,4]oxazin-3(4H)-one (11s),4-benzyl-7-((4-(2-fluorophenyl)piperazin-1-yl)methyl)-2Hbenzo[b][1,4]oxa zin-3(4Hone (lit),7-((4-benzylpiperazin-1-yl)methyl)-4-propyl-2Hbenzo[b][1,4]oxa zin-3(4Hone (11u) were efficiently synthesized by reduction, halogenation, alkylation, Williamson etherification and Smiles rearrangement using 3-bromo-4-hydroxyben-zaldehyde as starting material. All the 21 compounds were characterized by TCL identification,’H NMR,13C NMR and HRMS.All the synthesized compounds and the controlled drugs were assayed on the platelet aggregation inhibition effect and the structure-activity relationships (SAR) by microwell plate method. The results revealed that all the compounds possessed good anti-platelet aggregation activity which was positively correlated with concentration. The compound 11u, with the IC50 value at 9.20±0.11 μmol·L-1, showed the strongest inhibition effect among all the new synthetic compounds that was even close to the inhibition effect of aspirin as positive control.In addition, through the investigation on the specific interactions of compound 11u with GPIIb/IIIa receptor by molecular docking studies, we herein concluded that their antiplatelet activity was reached by nonspecificly binding with GPIIb/IIIa receptor. Through establishing the binding modes and SAR, we could further identify the molecule llu as the lead compound for the next generation of platelet inhibition agents. |
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