Design,Synthesis And Evaluation Of Antitumor Compounds Based On Naphthoquinone Structure Of Chinese Herbal Medicine

Natural product naphthoquinone is a kind of compounds with quinone structure.Because of its unique chemical structure and mechanism of action,it has become a hotspot in the field of medicinal chemistry.Studies have shown that the 1,4-naphthoquinone pharmacophore is the key to its anti-cancer effect.The National Cancer Institute?NCI?has extensively studied derivatives of1,4-naphthoquinone as anti-cancer candidate drugs.However,many 1,4-naphthoquinone compounds in nature have poor lipid solubility,low in bioavailability and large toxic and side effects,which limited their clinical application and there is no patent medicine.In order to find compounds with good anti-tumor biological activity,good solubility,and low toxicity to normal cells,in this paper,a series of modifications were designed and synthesized taken2-hydroxy-1,4-naphthoquinone as the lead compound.Thus,twenty-five new1,4-naphthoquinones were found and have not been reported in the literature.All compounds were characterized by,¹³C NMR,¹H NMR and HRMS.These compounds were evaluated by MTT assay in vitro,and were tested on human non-small cell lung cancer?A549?,human prostate cancer cell?PC-3?,human chronic myeloid leukemia cell?K562?,human liver cancer cell line?Hep G2?,and rat renal tubular duct epithelial cell?NRK-52E?.The results showed that all of the 13 compounds had good inhibitory activity on four cancer cells.It is worth noting that these 13 compounds showed higher biological activity than that of the positive control 5-fluorouracil(IC₅₀=7.35?M)in prostate cancer cells.Among them,the IC₅₀value of C1-J8 on all four human cancer cells was around 10?M,and the cytotoxicity on normal cells was the lowest?11.76%?.Plate clone formation experiments clearly confirmed that different concentrations of C1-J8 had a strong ability to inhibit the proliferation of prostate cancer cells PC-3,and the use of flow cytometry to detect compounds of different concentrations C1-J8 can significantly promote prostate cancer cells PC-3,Non-small cell lung cancer A549 undergoes advanced apoptosis.Through the above studies,1,4-naphthoquinone derivatives C1-J8 with better antitumor activity,better solubility and lower toxicity were obtained,which laid a material foundation for the research of this kind of compounds for prostate cancer.