Synthesis,Bioactivity Studies Of 5-(Dimethylamino)Naphthalene-1-Sulfonamide And 3-Hydroxy-2-oxo-Indole Derivatives

Drought stress is a major threat to crop production worldwide.The role of plant hormone abscisic acid(ABA)in water stress could be used to alleviate adverse effects of drought.ABA binds directly to the PYR/PYL family of ABA receptors,resulting in inhibition of type 2C phosphatases(PP2C)and activation of downstream ABA signaling to enhance abiotic stress resistance.The application of ABA in actual crop production is greatly limited,due to it's chemical instability and rapid catabolism.Therefore,the development of ABA functional analogues with novel skeletons and excellent performance is of great significance.Based on the physiological functions,synthesis,signaling pathway,and analogs of ABA,two series of target compounds were designed and synthesized.Twenty five small molecule fluorescent probes(SMFPs)were synthesized(based on the structure of Pyrabactin)as candidates for establishing fluorescent detection methods.Fourty seven 3-hydroxy-2-oxo-indole derivatives were synthesized by computer-assisted virtual screening strategy and structural optimization.All the above compounds were characterized by 1H NMR,13C NMR and HRMS.The target PYR1 receptor protein was challenged with SMFPs.Changes in fluorescence intensity and emission wavelength for each SMFP was detected by fluorescence spectrometry,for unbound and receptor-bound condition.Most of the SMFPs had larger changes of fluorescence in receptor-bound state,suggesting that,they are suitable candidates in establishing fluorescence detection methods.The result of root growth inhibition assay of series ? revealed that certain compounds of this series possess good inhibitory activity on root growth at a concentration of 25 ?mol/L.Most of the compounds tested had strong binding affinity to PYR1.Five compounds {?-1-3(Kd=3.87?M),?-2-2(Kd=3.61?M),?-2-23(Kd=3.43 ?M),?-3-4(Kd=1.97 ?M),?-4-1(Kd=3.81 ?M)} were detected with over 10-fold affinity to PYR1,than ABA(Kd=33.78?M).Acute drought response(assayed by leaf fresh weight loss)indicated that the Arabidopsis Thaliana(Wild type Col(0))treated with compound ?-1-3 and ?-2-10 showed excellent drought resistance than DMSO,which displayed the potential to be deeper investigated.The structure-activity relationships of the two series were systematically summarized,as well as the preliminary in vivo studies on the ability of resisting water loss.Furthermore,this work had laid the foundation for the establishment of fluorescence detection methods and provided a supportive reference for the discovery of a novel ABA analog.