Val R. Adams's Camptothecins in Cancer Therapy (Cancer Drug Discovery and PDF

By Val R. Adams

A serious evaluate our present figuring out of camptothecins, their shortcomings, and of the probabilities for bettering their medical functionality. The authors speak about new camptothecin analog improvement, drug supply matters for optimizing their anticancer job, and their strength use in various varied cancers. extra chapters describe what's identified concerning the biochemistry, the pharmacology, and the chemistry of the camptothecins, together with the mechanism of topoisomerase and the way camptothecins poison this enzyme, using animal types in defining the anticancer capability of camptothecins, and the query of camptothecin resistance.

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Additional resources for Camptothecins in Cancer Therapy (Cancer Drug Discovery and Development)

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Copyright 1999 American Chemical Society. 50 Hecht Fig. 11. Camptothecin analogues modified at position 20. stabilize the covalent enzyme-DNA binary complex. Wang et al. (8) tested the importance of the 20 OH group in a series of experiments involving CPT (1), 20-deoxy CPT (21) and CPT derivatives bearing substituents other than an OH group at position 20. These included 20-chloro CPT (22), 20-bromo CPT (23) and 20-amino CPT (24), all of which were essentially racemic at position 20 (Fig. 11). Compounds 1 and 21–24 were tested for their abilities to stabilize the covalent binary complex between human TOP-I and the DNA oligonucleotide duplex whose scissile strand had the sequence 5'GGCGCG GAGACTTGGAGAAATTTGGCGCGG; cleavage occurred at the T13G14 sequence (8).

1997 Involvement of amino acids 361 to 364 of human topoisomerase I in camptothecin resistance and enzyme catalysis. Biochem Pharmacol 53:1019–1027. 15. Krogh BO, Shuman S 2000. Catalytic mechanism of DNA topoisomerase IB. Mol Cell 5:1035–1041. 16. Fiorani P, Amatruda JF, Silvestri A, Butler RH, Bjornsti MA, Benedetti P. 1999 Domain interactions affecting human DNA topoisomerase I catalysis and camptothecin sensitivity. Mol Pharm 56:1105–1115. 17. Sheldrick GM. SHELXL-97. University of Göttingen, 1997.

2002 SUMO-1 conjugation to intact DNA topoisomerase I amplifies cleavable complex formation induced by camptothecin. Oncogene 21:7913–7922. Chapter 2 / Topoisomerase–DNA–Drug X-Ray Structure 2 23 Crystallographic Insight Into the Mechanism of Drug-Induced Topoisomerase I DNA Damage Alex B. , PhD, Michael D. Feese, PhD, Bart L. Staker, PhD, and Lance Stewart, PhD CONTENTS BACKGROUND THE TERNARY TOP-I–DNA–DRUG COMPLEX DRUG INTERACTIONS POISON EFFECTS ON DNA RELAXATION CONCLUSIONS REFERENCES 1. BACKGROUND Topoisomerase I (TOP-I) is an essential eukaryotic enzyme that acts to remove supercoils generated during transcription and DNA replication (1).

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