Camptothecins: a Review of Their Chemotherapeutic Potential

Overview

Journal Drugs

Specialty Pharmacology

Date 2002 Sep 25

PMID 12269849

Citations 59

Authors

Hulya Ulukan

Peter W Swaan

Affiliations

Soon will be listed here.

Abstract

Camptothecin analogues and derivatives appear to exert their antitumour activity by binding to topoisomerase I and have shown significant activity against a broad range of tumours. In general, camptothecins are not substrates for either the multidrug-resistance P-glycoprotein or the multidrug-resistance-associated protein (MRP). Because of manageable toxicity and encouraging activity against solid tumours, camptothecins offer promise in the clinical management of human tumours. This review illustrates the proposed mechanism(s) of action of camptothecins and presents a concise overview of current camptothecin therapy, including irinotecan and topotecan, and novel analogues undergoing clinical trails, such as exatecan (DX-8951f), IDEC-132 (9-aminocamptothecin), rubitecan (9-nitrocamptothecin), lurtotecan (GI-147211C), and the recently developed homocamptothecins diflomotecan (BN-80915) and BN-80927.

Citing Articles

Immunoconjugates as an Efficient Platform for Drug Delivery: A Resurgence of Natural Products in Targeted Antitumor Therapy.

Mihaylova R, Momekova D, Elincheva V, Momekov G Pharmaceuticals (Basel). 2025; 17(12.

PMID: 39770542 PMC: 11677665. DOI: 10.3390/ph17121701.

Camptothecin and its derivatives: Advancements, mechanisms and clinical potential in cancer therapy.

Kamle M, Pandhi S, Mishra S, Barua S, Kurian A, Mahato D Med Oncol. 2024; 41(11):263.

PMID: 39382779 DOI: 10.1007/s12032-024-02527-x.

Biotechnological approaches for the production of camptothecin.

Banadka A, Narasimha S, Dandin V, Naik P, Vennapusa A, Melmaiee K Appl Microbiol Biotechnol. 2024; 108(1):382.

PMID: 38896329 PMC: 11186875. DOI: 10.1007/s00253-024-13187-2.

Recent advances of tryptanthrin and its derivatives as potential anticancer agents.

Zhou X RSC Med Chem. 2024; 15(4):1127-1147.

PMID: 38665827 PMC: 11042161. DOI: 10.1039/d3md00698k.

N-methyl-D-aspartate receptors and thymoquinone induce apoptosis and alteration in mitochondria in colorectal cancer cells.

Sirinyildiz F, Unay S Med Oncol. 2024; 41(5):123.

PMID: 38652404 DOI: 10.1007/s12032-024-02348-y.

References

Beidler D, Cheng Y . Camptothecin induction of a time- and concentration-dependent decrease of topoisomerase I and its implication in camptothecin activity. Mol Pharmacol. 1995; 47(5):907-14. View

MOERTEL C, SCHUTT A, Reitemeier R, Hahn R . Phase II study of camptothecin (NSC-100880) in the treatment of advanced gastrointestinal cancer. Cancer Chemother Rep. 1972; 56(1):95-101. View

Huchet M, Demarquay D, Coulomb H, Kasprzyk P, Carlson M, Lauer J . The dual topoisomerase inhibitor, BN 80927, is highly potent against cell proliferation and tumor growth. Ann N Y Acad Sci. 2001; 922:303-5. DOI: 10.1111/j.1749-6632.2000.tb07049.x. View

Ajani J, Fairweather J, Pisters P, Charnsangavej C . Irinotecan and cisplatin in advanced gastric or gastroesophageal junction carcinoma. Oncology (Williston Park). 2001; 14(12 Suppl 14):19-21. View

Curran D, Josien H, Bom D, Gabarda A, Du W . The cascade radical annulation approach to new analogues of camptothecins. Combinatorial synthesis of silatecans and homosilatecans. Ann N Y Acad Sci. 2001; 922:112-21. DOI: 10.1111/j.1749-6632.2000.tb07030.x. View

Wani M, Nicholas A, Wall M . Plant antitumor agents. 23. Synthesis and antileukemic activity of camptothecin analogues. J Med Chem. 1986; 29(11):2358-63. DOI: 10.1021/jm00161a035. View

Cozzarelli N . DNA gyrase and the supercoiling of DNA. Science. 1980; 207(4434):953-60. DOI: 10.1126/science.6243420. View

Demarquay D, Coulomb H, Huchet M, Camara J, Lavergne O, Bigg D . The homocamptothecin, BN 80927, is a potent topoisomerase I poison and topoisomerase II catalytic inhibitor. Ann N Y Acad Sci. 2001; 922:301-2. DOI: 10.1111/j.1749-6632.2000.tb07048.x. View

Wall M, Wani M . Antineoplastic agents from plants. Annu Rev Pharmacol Toxicol. 1977; 17:117-32. DOI: 10.1146/annurev.pa.17.040177.001001. View

10.

Emerson D, Besterman J, Brown H, Evans M, Leitner P, Luzzio M . In vivo antitumor activity of two new seven-substituted water-soluble camptothecin analogues. Cancer Res. 1995; 55(3):603-9. View

11.

Gerrits C, Creemers G, Schellens J, Wissel P, Planting A, Kunka R . Phase I and pharmacological study of the new topoisomerase I inhibitor GI147211, using a daily x 5 intravenous administration. Br J Cancer. 1996; 73(6):744-50. PMC: 2074382. DOI: 10.1038/bjc.1996.130. View

12.

Lavergne O, Pla Rodas F, Kasprzyk P, Pommier J, Demarquay D, Prevost G . Homocamptothecins: synthesis and antitumor activity of novel E-ring-modified camptothecin analogues. J Med Chem. 1999; 41(27):5410-9. DOI: 10.1021/jm980400l. View

13.

Schmitt B, Buhre U, Vosberg H . Characterisation of size variants of type I DNA topoisomerase isolated from calf thymus. Eur J Biochem. 1984; 144(1):127-34. DOI: 10.1111/j.1432-1033.1984.tb08440.x. View

14.

Abigerges D, Armand J, Chabot G, Da Costa L, Fadel E, Cote C . Irinotecan (CPT-11) high-dose escalation using intensive high-dose loperamide to control diarrhea. J Natl Cancer Inst. 1994; 86(6):446-9. DOI: 10.1093/jnci/86.6.446. View

15.

Gamucci T, Paridaens R, Heinrich B, Schellens J, Pavlidis N, Verweij J . Activity and toxicity of GI147211 in breast, colorectal and non-small-cell lung cancer patients: an EORTC-ECSG phase II clinical study. Ann Oncol. 2000; 11(7):793-7. DOI: 10.1023/a:1008373031714. View

16.

Loos W, Kehrer D, Brouwer E, Verweij J, de Bruijn P, Hamilton M . Liposomal lurtotecan (NX211): determination of total drug levels in human plasma and urine by reversed-phase high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 2000; 738(1):155-63. DOI: 10.1016/s0378-4347(99)00513-7. View

17.

Juan C, Hwang J, Liu A, Whang-Peng J, Knutsen T, Huebner K . Human DNA topoisomerase I is encoded by a single-copy gene that maps to chromosome region 20q12-13.2. Proc Natl Acad Sci U S A. 1988; 85(23):8910-3. PMC: 282616. DOI: 10.1073/pnas.85.23.8910. View

18.

Crump M, Lipton J, Hedley D, Sutton D, Shepherd F, Minden M . Phase I trial of sequential topotecan followed by etoposide in adults with myeloid leukemia: a National Cancer Institute of Canada Clinical Trials Group Study. Leukemia. 1999; 13(3):343-7. DOI: 10.1038/sj.leu.2401308. View

19.

Wang J . DNA topoisomerases. Annu Rev Biochem. 1985; 54:665-97. DOI: 10.1146/annurev.bi.54.070185.003313. View

20.

Takeuchi S, Takamizawa H, Takeda Y, Ohkawa T, Tamaya T, Noda K . [An early phase II study of CPT-11 in gynecologic cancers. Research Group of CPT-11 in Gynecologic Cancers]. Gan To Kagaku Ryoho. 1991; 18(4):579-84. View