Design,Synthesis And Anti-melanoma Activity Of Derivatives Based On Compound THPN

Melanoma is a common tumor in the skin and has attracted the attention of a wide range of researchers due to its high mortality and easy transfer characteristics.Early melanoma can be treated by surgical resection,but for patients with advanced disease.the effect of surgical resection is not obvious,and radiotherapy and chemotherapy are generally used.However,the defects of the special apoptosis mechanism existing in melanoma cells make the existing chemotherapy drugs ineffective.Molecular targeted drugs have become a trend in drug development due to their exact pharmacological effects and low toxic side effects.The THPN referred to herein is a targeted small molecule compound capable of specifically inducing autophagic death of melanoma cells,and has the potential to develop an anti-melanoma drug with a novel action pathway.Although THPN has good specificity,its biological activity has yet to be improved,and the ambiguity of structure-activity relationship is not conducive to its subsequent development.In this paper,THPN was used as a lead compound to design long-chain gallate and gallate amides based on the principles of biomolecularization and pharmacokinetics.All the 39 compounds synthesized were confirmed by structural identification methods such as nuclear magnetic resonance spectroscopy,nuclear magnetic resonance carbon spectroscopy and mass spectrometry.Through the preliminary exploration of the three main parts of the THPN structure:benzene ring,acyl group and alkyl chain.A part of the synthesized compounds was subjected to preliminary screening of the drug by the A375 cell proliferation inhibitory activity test.The results showed that some of the synthesized compounds(LH-6,LH-7.LH-8)showed better tumor growth inhibitory activity,and the compound LH-8 inhibited the proliferation of A375 cells better than THPN.At the same time,observation of the cell morphology changes of the time gradient dosing also confirmed the efficacy of the compound.Finally,the correlation of the same target of THPN was studied for compounds with superior proliferation inhibition activity,and the biological mechanism is still in progress.In summary,THPN is the lead compound,and the compound structure is optimized,and the compound LH-8 is obtained by active screening.It is an important theoretical basis for clarifying the structure-activity relationship of THPN and promoting the development of anti-melanoma targeted drugs..Such compounds have potential applications,and in-depth anti-tumor mechanisms are underway.