Design And Evaluation Of Phenyl Thiophenol Fluorescent Indicator And Schiff's Base Derivatives

This article includes two parts.In the first part,we discussed the design,synthesis,and evaluation of a fluorescent indicator for phenyl thiophenol,and in the second part,we discussed the design,synthesis,and biological evaluation of a novel schiff's base derivatives.Since the industrial revolution,due to the lack of long-term view,we human beings have been eager to promote industrialization,which has brought out rapid economic growth in the short term,however,at the same time,human destruction of the natural environments was also increasing.In recent years,increasingly frequent natural disasters sounded the alarm that it is extremely urgent that we humankind devote ourselves to the detection and control of environmental pollution.Among the large amounts of pollutants which are emitted into the environment,phenyl thiophenol caused the attention of the relevant researchers.As a kind of environmental pollutant of high toxicity,large amounts of phenyl thiophenol are being produced in the refining of oil and coal,rubber and plastics industry.Because of the high toxicity and universalism of phenyl thiophenol,phenyl thiophenol detection is of great significance in environmental detection.In recent years,fluorescent probe has become a hot spot in the field of analytical chemistry,this trend may be attributed to its fast response,high sensitivity,simple operation,good reproducibility,and the advantages of simple equipment.By fluorescence imaging,chemical fluorescent probe can analyze analytes in biological system efficiently,and almost do no destruction to biological samples.In recent years,chemical fluorescent probes is widely used in analyzing metal ions,organic small molecules and biological macromolecules.In this article,we designed and synthesized a small molecular fluorescent probe TPP.The probe is based on ESIPT,and it can detect phenyl mercaptan effectively.The probe can response with phenyl mercaptan rapidly under 25?,physiological pH,making the system fluorescence intensity increase significantly(60 folds).The reaction will finish in 3.5 minutes,which is better than the other thiophenol probes which have been reported.In this paper,we use some common amino acid and analogues of thiophenol as reference,to test the probe's selectivity and anti-jamming capacity.We find that TPP has good selectivity,and it can distinguish phenyl mercaptan from alkyl mercaptan,etc.Even on condition that the distractors' concentration is significantly higher than that of phenyl mercaptan,the probe can still produce stable corresponding to phenyl mercaptan.In addition,TPP has low detection limit(2×10-7 M),and it can detect phiophenol under mild reaction conditions.In actual environment monitoring,the fluorescent probe can measure the concentration of phenyl mercaptan.We got the standard curve:y=0.4109x+23.675,R2=0.99822.Then we tested the water sample from Yangtze River and Xuanwu Lake,and the measured data was very close to actual value.Compared to the previous studies,TPP is by far the fastest small molecular fluorescent probe of phenyl mercaptan in natural water bodies.This success shows that TPP has high application value in the environmental monitoring.EGRF signaling pathways play an important part in cell signal transductions,regulation of cell growth,proliferation,and respond to extracellular stimuli(such as growth factors and cytokines).Choosing this as the target,in other words,by inhibiting EGFR,we can hope that tumor cell proliferation be inhibited,which is helpful to promote the treatment of human cancer.In the past few decades,schiff base and its derivatives have attracted constant interest over the past decades because of their wide range of pharmacological activities,such as anti-tumor,anti-inflammatory,antibacterial,etc.In addition,quinoline,nitro imidazole derivatives as inhibitors occupies the important position in modern pharmaceutical chemistry.Moreover,schiff' s base occupies an important position in the modern medicinal chemistry as inhibitors.This study was based on the principle of combinatorial chemistry,aiming to design and synthesize schiff's base derivatives containing containing quinoline and quinolone and nitroimidazole structure as anticancer drugs.We herein described the synthesis of these target compounds named 5a-j.Majority of the studied compounds showed effective antiproliferation and inhibition of EGFR and HER-2 activities Among all the compounds,5h showed most effective inhibition by binding in to the active pocket of EGFR receptor with minimum binding energy(?Gb=-58.369kcal/mol).In addition,Compound 5d showed most effective inhibition to HER-2(IC50=0.37±0.04 ?M).Docking simulations were also performed using the X-ray crystallographic structure of the EGFR in complex with an inhibitor to explore the binding modes of these compounds.QSAR model was built based on the activity data to study the structure-activity relationship and guide the further study.