Synthesis And Antitumor Activity Of Camptothecin Derivatives Modified At The 7-position

Topoisomerase I is an ubiquitous enzyme that solve topological problems generated by key nuclear processes such as DNA replication, transcription, recombination, repair, chromatin assembly, and chromosome segregation. Camptothecin was a cyto-toxic agent and exerted its antitumor activity by inhibiting Topoisomerase I. It was used for curing various malignant tumors, such as the bone cancer, cancer of the liver, theurine bladder cancer and leukemia etc. However, clinical study shows that camptothecin leads to severe adverse effects such as marrow inhibition, vomiting, diarrhca and hemoglobinuria.In vivo camptothecin remains a balance of E-lactone form and Carboxylic salt form. Maintenance of E-lactone is impor- tant for the antitumor activity. People are studying Structure-Activity Relationships of derivatives of camptothecin. To improve the profile of 20 (S)-campptothecin. Therefore, derivatives of camptothecin are becoming the focus of research.This paper summarized the new development on Topoisomerase I and camptothecin research, and discussed Structure-Activity Relationships of camptothecin analogs. Based on Rational Drug Design, We design and synthesesze three new compounds of 7-benzoyl-camptothecin, and 7- dimethyl-benzoyl-camptothecin, Which could Make into the hydrochloride form and increase it water-soluble and be advantageous to the absorption of the medicine and make into various type.The in vitro cytoxicity against HL-60, BGC-823, Bel-7420 and KB cell lines of the 7-benzoyl-camptothecin were evaluated. The results reveal that it posses inhibitory activity against rumor cells .Author: LENGZhi (Organic Chemistry) Directed by Prof. NIE Li-juan...