Structural Modification Of Quinoline Alkaloids And Preliminary Study Of Their Antitumor Activity

Objective:Quinoline alkaloids are one of the active ingredients in biopharmaceuticals and have a variety of pharmacological activities such as antibacterial,anti-inflammatory,anti-malarial,antiviral and antitumor.Due to the high clinical use of drugs containing quinolines,the isolation of this ingredient from biopharmaceuticals alone can no longer meet the clinical demand,therefore,the study of the structure of quinoline alkaloids has been a hot topic,and the novelty of their structures and their status in organic chemistry are of paramount importance.Synthesizers have used various facile raw materials to synthesize natural products along with structural modifications to develop a diversity of novel quinoline-like active molecules.In the present study,a large number of phosphorylated quinoline alkaloids were prepared by systematically modifying the structure of the quinoline backbone in combination with phosphineoxygenated organic compounds.At the same time,various human-derived tumor cells were selected for preliminary exploration of the antitumor activity of phosphorylated quinolines.The results of these preliminary explorations add part of the experimental basis for thesearch of natural andeffective anticancer active ingredients.Methods:A series of phosphorylated quinoline-based alkaloids were prepared from quinoline-based compounds by structural modification using phosphine oxide organic compounds.The method uses a non-homogeneous carbon catalyst,graphene oxide（GO）,without any transition metal or organic dyes,to achieve the construction of the phosphorylated quinoline alkaloids,i.e,to obtain the phosphorylated quinolone alkaloids at the C-2 and C-4 positions,respectively.The inhibitory activities of all these alkaloids against Hep G2（human hepatocellular carcinoma）,T-24（human bladder cancer）,A549（human lung cancer）,MGC-803（human gastric cancer）,and Hela（human cervical cancer）cells were tested by MTT assay,and the changes in Hela apoptosis rate,mitochondrial membrane potential,Hoechst 33342 staining,cycle block,reactive oxygen species（ROS）and Ca²⁺content wereused to explore themechanism of action.Results:Structural modification of quinoline alkaloids was achieved using a carbon catalyst graphene oxide（GO）in concert with visible light to obtain a series of phosphonylated quinoline alkaloids with good regioselectivity and broad substrate applicability.These new quinoline-based alkaloids werethen initially explored in vitro and screened by toxicity experiments on cancercell lines such as Hep G2（human liver cancer）,T-24（human bladder cancer）,A549（human lung cancer）,MGC-803（human gastric cancer）and Hela（cervical cancer）,and it was found that4-（diphenylphosphinyl）6-methylquinolin-2（1H）-one 3c exhibited a good inhibitory effect on On this basis,Hoechst 33342 staining,mitochondrial membrane potential,cell cycle block,intracellular reactive oxygen species（ROS）test,and intracellular calcium ion(Ca²⁺)concentration assay were performedto further verify the significant anti-proliferativeeffect of 3c on Hela cells effect.Conclusion:In this study,the chemical structures of quinoline alkaloids were modified,followed by in vitro anti-tumorscreening of these alkaloids,and their mechanisms of action were initially explored using changes in Hela apoptosis rate,cycle block,mitochondrial membrane potential,reactive oxygen species（ROS）and Ca²⁺content,with a view to finding active ingredients or lead compounds,and providing some scientific basis and reference value for the development research of quinoline alkaloids.