Synthesis And Antitumor Application Of 5-selenidoindolo [2,1-a] Isoquinoline-6(5H)-one

Objective:Organic selenides are a kind of important compounds,which are widely used in medicine,fluorescent agent and other fields.In this paper,a series of 5-seleno-indole[2,1-a]isoquinoline-6（5H）-ones were synthesized by the selenization/cyclization of 2-arylindoles and diselenides catalyzed by Fe（OTf）₃,Then,MTT method was used to screen the antitumor activity of the synthesized organoselenium compounds in vitro,and the mechanism of the compounds with better pharmacological activity was further studied,which provided reference value for the development of organoselenium lead compounds in the future.Methods:We selected 2-arylindole and diphenyl diselenide as substrates,and through a series of screening conditions,we finally confirmed that Fe（OTf）₃ as catalyst,DCE as solvent,at 80℃for 1.5 h was the best reaction condition.Under the optimum reaction conditions,5-selenidoindolo[2,1-a]isoquinoline-6（5H）-ones with various structures were synthesized.MTT assay was used to detect the antitumor activity of 5-fluorouracil（5-FU）against T-24（human bladder cancer cell）,MGC-803（human gastric cancer cell）,Hela（cervical cancer cell）and SK-OV-3（human ovarian cancer cell）in vitro.The antitumor activity of 5-FU was used as positive control.The antitumor mechanism of compound 3g against He La cell in vitro was studied.Results:Twenty novel 5-selenidoindolo[2,1-a]isoquinoline-6（5H）-ones were synthesized and their structures were characterized by NMR and high resolution.MTT assay showed that the 5-selenidoindolo[2,1-a]isoquinoline had good antitumor activity,and compound 3g had significant antitumor activity.The IC₅₀ values of compound 3g to T-24,MGC-803,He La and SK-OV-3 were 13.7±1.2μM,11.5±0.6μM,9.4±0.8μM and 32.4±1.5μM,respectively.Anti tumor mechanism studies showed that compound 3g could induce apoptosis by increasing intracellular calcium concentration,increasing intracellular reactive oxygen species concentration and affecting cell tissue migrationand repair ability.Conclusion:twenty 5-selenidoindolo[2,1-a]isoquinoline-6（5H）-ones were synthesized by a new method.The synthetic steps are simple and easy to operate with good yields.Some compounds have antitumor activities,among which compound 3g has significant antitumor activity.