Design, Synthesis And Biological Activity Evaluation Of Baicalein Sulfonated Derivatives

Baicalein is a major flavonoid compound,which is extracted from the Scutellaria baicalensis’s dried roots.It has ideal potential pharmacological activity in anti-arrhythmic,anti-tumor,neuron protection,liver protection,immune regulation,etc.However,there are three phenolic hydroxyl groups in the structure of baicalein,resulting in its low bioavailability,which limits the clinical application of baicalein to a certain extent.Thus,the synthesis and structural modification of baicalein derivatives have become a hot topic of research and discussion among scholars.In this thesis,a series of baicalein sulfonated derivatives（GL01～GL33）were designed and synthesized with baicalein as the lead compound,all of which were confirmed by ¹H-NMR,¹³C-NMR and high-resolution mass spectrometry.A series of biological activity experiments were subsequently carried out.In the antiviral experiments in vitro,we conducted preliminary screening studies against influenza virus and novel coronavirus with the synthesized sulfonated baicalein derivatives,respectively.The results showed that 5compounds（GL10,GL11,GL17,GL27,GL33）had great anti-influenza virus activity,and the compound GL33(IC₅₀=25.83μM)with the most inhibitory potential;4 compounds（GL09,GL12,GL25,GL31）had good anti-COVID-19activity,and the compound GL12(IC₅₀=30.53μM)with the most inhibitory potential among them.Then,the screened compounds are virtually docked with antiviral targets to simulate the interaction mode between protein and compound molecules through molecular docking.The results of the antibacterial test in vitro showed that compared with the initiating compound baicalein,the compounds GL10,GL15,GL32 and GL33showed certain antibacterial properties against Pseudomonas aeruginosa;the compounds GL15,GL32 and GL33 showed certain bacteriostatic properties against Staphylococcus aureus.Tumor inhibitory activities were assessed by MTT assay.The results showed that compound GL06 exhibited good tumor suppressive activity against MCF-7cells(IC₅₀=36.57μM);compound GL03 exhibited great tumor inhibition activity against Hela cells(IC₅₀=56.3μM)and compound GL09 showed great tumor inhibition activity against Hep G2 cells(IC₅₀=55.575μM).This topic provides theoretical support for the structural modification and preclinical research of baicalein derivatives,and lays an academic foundation for the exploration of the antiviral,antibacterial and antitumor biological activities of baicalein.