Study Of The Structural Modification And Biological Activity Of Erythromycin

Erythromycin had been extensively used in the treatment of bacterial infections for over 50 years. In addition to its anti-microbial activity in clinical studies, erythromycin and its derivatives exhibited prokinetic activity, anti-inflammatory activity and luteinizing hormone-releasing hormone antagonistic activity. Moreover, they had been discovered helpful effect in the treatment of tumor.In our efforts, dimmer of erythromycin derivative, a novel class of erythromycin derivative was discovered. After further investigation, it was found to be active in antitumor. Therefore we picked it as a lead compound and through structural modification at the C-3, C-6 and C-9 position, 15 novel compounds were designed.Following the reported methodologies the N-monodemethyled compounds could be separated from the erythromycin derivative. Treatment of N-demethyl derivatives (3-4-3-13) in DMF with N,N-diisopropylethylamine and 1-bromo-2-chloroethane or 1,4-dibromo-2-butene effected the formation of the target products (ZCL-201～ZCL-206 and ZCL-401～ZCL-406). ZCL-501～ZCL-503 were prepared by utilizing chloracetyl chloride as acylation agents in the presence of N,N-diisopropylethylamine in dichloromethane at room temperature.All of 15 compounds' chemical structures were characterized by the applications of ¹H-NMR, ¹³C-NMR and MS. The data of ¹³C-NMR spectra were discussed briefly.Some compounds were evaluated for their in vitro antitumor activities against human Jurkat cell lines by MTT assay. The results of pharmacological test demonstrated that all the compounds owned slight activity in inhibitaing the generation of T achroacyte.