Synthesis And Properties Of Novel Flavonoid-indole Compounds

Flavonoids are a kind of polyphenols widely found in plants.Due to their structural diversity,flavonoids could exhibit good fluorescence performance,bioelectrochemical performance,significant physiological and pharmacological activities.Consequently,they are becoming widely used in detection,medicine and other fields.In order to further enhance the excellent properties of flavonoids,in this study,the indole derivatives with various biological activities were introduced into the flavonoid skeleton based on the principle of activity superposition.Two series of 16new flavonoid-indole derivatives were synthesized,and their UV-vis,fluorescence,metal ion response,electrochemical property and anticancer activity had been extensively explored.1.7-hydroxyflavone derivatives were synthesized from 2,4-dihydroxyacetophenone and benzoyl chloride derivatives.In the presence of EDCI/DMAP,3-indoleformic acid and 6-indoleformic acid reacted with the 7-hydroxyflavone derivatives,respectively,providing two series of 16 novel flavonoid-indole compounds FL₁-FL₈ and FL₉-FL₁₆.The structures of compounds FL₁-FL₁₆ were characterized by IR,elemental analysis,¹H NMR and ¹³C NMR.In addition,the crystal structure of compounds FL₁ and FL₁₀ were determined by X-Ray.2.The study of UV-vis absorption spectrums showed that the introduction of-OCH₃ group into the position of flavonoid(FL₈ and FL₁₆)leads to a redshifted absorption peaks.Meanwhile,the absorption peaks of FL₇ and FL₁₅ were redshifed and hypochromic effect by introduction of–NO₂group.On the other hand,the introduction of-CF₃ group resulted in blue-shifted absorption peaks(FL₆and FL₁₄).Fluorescence emission spectrums showed that these compounds exhibited strong photoluminescence,and the fluorescence intensities of FL₈and FL₁₆ were stronger than others due to the introduction of–OCH₃group.3.The metal ion recognition experiments showed that compounds FL₁-FL₁₆were able to selectively recognize Cu²⁺with obvious fluorescence quenching.Especially,the detection limits of compounds FL₁ and FL₉ for Cu²⁺were 6.00×10^-6 mol/L and2.84×10^-6 mol/L,respectively,indicating that these compounds were potential fluorescent probes for Cu²⁺.4.The electrochemical properties of FL₁-FL₈ and FL₉-FL₁₆ were studied by cyclic voltammetry,the cyclic voltammetry curves showed that the electrochemical reactions of the two series of compounds on the electrode surface were irreversible.The oxidation peak potential of compound FL₂was lower,and its antioxidant activity was better.5.CCK-8 method was used to test the antitumor activity of 7-hydroxyflavonoid derivatives?L₁-L₈?and 16 target compounds FL₁-FL₁₆ on 6 cancer cells.The results showed that compared with L₁-L₈,the introduction of 3-indoleformic acid into 7-hydroxyflavonoid derivatives through ester bond increased their antitumor activities,so the overall antitumor activities of FL₁-FL₈ were better than that of FL₉-FL₁₆.The structure-activity relationship found that the introduction of-Br,-CH₃and-CF₃ could improve the antitumor activity of the compound.It was worth noting that compound FL₂(IC₅₀=10.70?M)showed better antitumor activity than adriamycin(IC₅₀=11.04?M)on gastric cancer cell line SGC-7901,indicating that compound FL₂ had the potential to be an anticancer drug.