Research Of Design,Synthesis,and Antiproliferative Activity Of Photoswitchable Gleevec Derivatives

Optical Switch or Photo Switch is a class of small organic molecular compounds,which undergo reversible photochemistry so that many rounds of active/inactive states can be produced.A range of actuators undergoes photoswitchable behaviour such as ring-opening/closing and isomerization between two distinct states each having different spectroscopic,chemical and physical properties.Among various photochromic compounds,azobenzenes are one of the most promising candidates for practical applications because of their excellent thermal stability.It has been widely used for the photo-control of biomolecules,which rapidly and fully reversibly photoswitched in buffer,without degradation over hundreds of cycles by low-power illumination.Therefore,utilizing this unique property of azobenzene as a photoswitch in biological systems to drive functional changes in compound,as a new type of targeting medicine.Here we introduce new concepts in the design of small molecule drugs whose inhibitory effects can be controlled with high spatial and temporal resolution to improve targeting to defined sites in a subject.Dysfunctional tyrosine kinases(TK)are often associated with human cancer and are targets of highly effective anti-cancer drugs such as Gleevec.The high concentration of these drugs in serum however,can lead to offtarget effects in healthy cells.So we synthesized a newly Gleevec derivatives which undergo reversible optical transitions between two distinct states upon low-power illumination at appropriate wavelengths,without degradation over hundreds of cycles.In particular,the substitution of a small actuating group in gleevec generates a switchable activity that exists in either a cis or trans conformation.Meanwhile,investigated the experimental conditions of illumination-induced transformation,and established a stable and reliable biological experimental model.And these analogs can be used for photocontrol of Gleevec's function in intracellular environments in the research.