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Synthesis, topoisomerase I inhibitory activity and in vitro cytotoxicity of camptothecin derivatives bearing five-membered heterocycle containing 10-substituents.
Anticancer Drug Des. 1998 Mar; 13(2):145-57.AD

Abstract

A series of new camptothecin derivatives bearing certain five-membered heterocycles was synthesized and evaluated for in vitro cytotoxic activity. The cytotoxicity results show that camptothecin derivatives bearing pyrrole and thiophene rings were more potent than camptothecin, whereas those bearing furan were less active than camptothecin. Agarose gel electrophoresis shows different inhibitory activities of the camptothecin analogs towards topoisomerase I DNA cleavage. The pyrrole-containing compounds inhibit topoisomerase I DNA cleavage more strongly than camptothecin, but the thiophene and furan compounds do not show any inhibitory activities for DNA cleavage functions of topoisomerase I. Polyacrylamide gel sequencing electrophoresis shows that the pyrrole compounds induce single-strand breaks after incubating with a labeled DNA fragment. The results suggest that the pyrrole compounds fit the compound-enzyme-DNA complex better than camptothecin and the other analogs.

Authors+Show Affiliations

Department of Chemistry, University of Alberta, Edmonton, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9524556

Citation

Zhao, R, et al. "Synthesis, Topoisomerase I Inhibitory Activity and in Vitro Cytotoxicity of Camptothecin Derivatives Bearing Five-membered Heterocycle Containing 10-substituents." Anti-cancer Drug Design, vol. 13, no. 2, 1998, pp. 145-57.
Zhao R, Guan LL, Oreski B, et al. Synthesis, topoisomerase I inhibitory activity and in vitro cytotoxicity of camptothecin derivatives bearing five-membered heterocycle containing 10-substituents. Anticancer Drug Des. 1998;13(2):145-57.
Zhao, R., Guan, L. L., Oreski, B., & Lown, J. W. (1998). Synthesis, topoisomerase I inhibitory activity and in vitro cytotoxicity of camptothecin derivatives bearing five-membered heterocycle containing 10-substituents. Anti-cancer Drug Design, 13(2), 145-57.
Zhao R, et al. Synthesis, Topoisomerase I Inhibitory Activity and in Vitro Cytotoxicity of Camptothecin Derivatives Bearing Five-membered Heterocycle Containing 10-substituents. Anticancer Drug Des. 1998;13(2):145-57. PubMed PMID: 9524556.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis, topoisomerase I inhibitory activity and in vitro cytotoxicity of camptothecin derivatives bearing five-membered heterocycle containing 10-substituents. AU - Zhao,R, AU - Guan,L L, AU - Oreski,B, AU - Lown,J W, PY - 1998/4/3/pubmed PY - 1998/4/3/medline PY - 1998/4/3/entrez SP - 145 EP - 57 JF - Anti-cancer drug design JO - Anticancer Drug Des. VL - 13 IS - 2 N2 - A series of new camptothecin derivatives bearing certain five-membered heterocycles was synthesized and evaluated for in vitro cytotoxic activity. The cytotoxicity results show that camptothecin derivatives bearing pyrrole and thiophene rings were more potent than camptothecin, whereas those bearing furan were less active than camptothecin. Agarose gel electrophoresis shows different inhibitory activities of the camptothecin analogs towards topoisomerase I DNA cleavage. The pyrrole-containing compounds inhibit topoisomerase I DNA cleavage more strongly than camptothecin, but the thiophene and furan compounds do not show any inhibitory activities for DNA cleavage functions of topoisomerase I. Polyacrylamide gel sequencing electrophoresis shows that the pyrrole compounds induce single-strand breaks after incubating with a labeled DNA fragment. The results suggest that the pyrrole compounds fit the compound-enzyme-DNA complex better than camptothecin and the other analogs. SN - 0266-9536 UR - https://www.unboundmedicine.com/medline/citation/9524556/Synthesis_topoisomerase_I_inhibitory_activity_and_in_vitro_cytotoxicity_of_camptothecin_derivatives_bearing_five_membered_heterocycle_containing_10_substituents_ L2 - https://www.ingentaconnect.com/openurl?genre=article&issn=0266-9536&volume=13&issue=2&spage=145&aulast=Zhao DB - PRIME DP - Unbound Medicine ER -