Synthesis and Biological Evaluation of Novel A-Ring Modified Hexacyclic Camptothecin Analogues

Kim, Dae‐Kee; Ryu, Do Hyun; Lee, Ju Young; Lee, Namkyu; Kim, Young Woo; Kim, Jae-Sun; Chang, Kieyoung; Im, Guang-Jin; Kim, Tae-Kon; Choi, Won-Son

doi:10.1021/jm0004751

Cited by 75 publications

(27 citation statements)

References 37 publications

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“…147 Initial screening of the compounds found a subgroup that maintained the cytotoxicity of CPT. One compound with a morpholine ring bridging positions 9 and 10 showed retention of TOP I inhibition and increased lactone stability in human serum compared to CPT (but not SN38).…”

Section: Camptothecin Modificationsmentioning

confidence: 99%

Cancer Therapies Utilizing the Camptothecins: A Review of the in Vivo Literature

2010

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This review summarizes the in vivo assessment--preliminary, preclinical, and clinical--of chemotherapeutics derived from camptothecin or a derivative. Camptothecin is a naturally occurring, pentacyclic quinoline alkaloid that possesses high cytotoxic activity in a variety of cell lines. Major limitations of the drug, including poor solubility and inactivity at physiological conditions, prevent full clinical utilization. Camptothecin remains at equilibrium in an active lactone form and inactive hydrolyzed carboxylate form. The active lactone binds to DNA topoisomerase I cleavage complex, believed to be the single site of activity inhibiting DNA religation, resulting in apoptosis. A series of small molecule camptothecin derivatives have been developed that increase solubility, lactone stability and bioavailability to varying levels of success. A number of macromolecular agents have also been described wherein camptothecin(s) are covalently appended or non-covalently associated with the goal of improving solubility and lactone stability, while taking advantage of the tumor physiology to deliver larger doses of drug to the tumor with lower systemic toxicity. With the increasing interest in drug delivery and polymer therapeutics, additional constructs are anticipated. The goal of this review is to summarize the relevant literature for others interested in the field of camptothecin-based therapeutics, specifically in the context of biodistribution, dosing regimens, and pharmacokinetics with the desire of providing a useful source of comparative data. To this end, only constructs where in vivo data is available are reported. The review includes published reports in English through mid-2009.

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Section: Camptothecin Modificationsmentioning

confidence: 99%

Cancer Therapies Utilizing the Camptothecins: A Review of the in Vivo Literature

2010

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“…3, respectively. Propyl 4-nitrophenyl carbonate 4 [46], isopropyl 4-nitrophenyl carbonate 7 [47], and tert-butyl 4-nitrophenyl carbonate 8 [48] were synthesized by the known procedure. The other chemicals that were used in this study were reagent grade and used without further purification.…”

Section: Synthesis and X-ray Crystallographymentioning

confidence: 99%

Enhancement of catalytic reactivity of zinc(II) complex by a cyclotriveratrylene-capped structure

Makita

Ikeda

Sugimoto

et al. 2012

Journal of Organometallic Chemistry

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“…A number of other analogs stand out from the many that have been made. Among these are the hexacyclic 1, 4-oxazines [260], Ring E homocamptothecins, 7-cyanocamptothecins [261], and the silatecans (25) [262]. The latter are structurally unusual, in that very few candidate drugs contain silicon atoms.…”

Section: Molecular Mode Of Action and Resistancementioning

confidence: 99%

Natural Products as Cytotoxic Agents

Cutler

2010

Burger's Medicinal Chemistry and Drug Discovery

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In the first decade of the twenty‐first century, the occurrence of cancers has increased not only in First World countries but also in those countries considered to have a lower standard of living, according to a world cancer report issued in 2008 for the IARC Nonserial Publication by Boyle and Levin. So widespread is cancer, in its various forms, that most adults have either had family members or had friends who have been afflicted by the disease. Projected figures for cancers indicate, in the aforementioned publication, that 12 million cancer cases were diagnosed in 2008 alone and that the number of cancer victims has doubled since 1978. Coupled to the psychological impact that a diagnosis has on an individual is the cost of treatment that must also be considered. Again, according to the National Cancer Institute (December 2008) these costs are estimated to be US$147 billion by 2020. An article, published in USA Today , claims that new cancer cases in 2008 were projected to be 40,480. And the cost for elderly Medicare patients will be US$21.1 billion for 5 years of treatment for the period 2004–2009. Sadly, one in eight patients with advanced stages of cancer will turn down the offer of recommended care because of costs. While cases may have been misdiagnosed in the twentieth century, the sophisticated techniques available today give a clearer graph of the incidence of the disease. With advanced diagnostics, there has been a concomitant advance in anticancer chemotherapy.

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Synthesis and Biological Evaluation of Novel A-Ring Modified Hexacyclic Camptothecin Analogues

Cited by 75 publications

References 37 publications

Cancer Therapies Utilizing the Camptothecins: A Review of the in Vivo Literature

Cancer Therapies Utilizing the Camptothecins: A Review of the in Vivo Literature

Enhancement of catalytic reactivity of zinc(II) complex by a cyclotriveratrylene-capped structure

Natural Products as Cytotoxic Agents

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