Synthesis, antitumor activity and pharmacokinetic study of 10‐propionyloxy camptothecin in rats

Zheng, Jian‐Guo; Shao, Changmin; Fan, Bin; Jing, Lijia; Li, Siyang; Yan, Xiufeng; Wang, Yang

doi:10.1002/bmc.4336

Cited by 3 publications

(2 citation statements)

References 16 publications

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“…CPT has been demonstrated to be a superior antitumor drug with poor water solubility and high toxicity. [ 37 ] Toward this issue, CPT‐PM were prepared. Encapsulated into the micellar cores, CPT can keep its structure stability and minimize its premature release in the circulation and transportation.…”

Section: Resultsmentioning

confidence: 99%

Iminoboronate Backbone‐Based Hyperbranched Polymeric Micelles with Fenton‐Like Enhanced ROS Response

Zhang

Guo

Liu

et al. 2020

Macro Chemistry & Physics

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is widespread in tumor cells, even clinical studies revealed that the concentration of H 2 O 2 in cancerous tissues is many times higher (ranging from 100 × 10 −6 to 1 × 10 −3 m) compared to that in normal tissues (35 × 10 −6 m). [15,16] The differentiated ROS level in different regions inspires the development of ROS-responsive micelles for targeted drug delivery. [17][18][19] Motifs such as thioether, thioketal, ferrocene, tellurium, selenium, and boronic ester are introduced to the structures of the polymers to endow the self-assembled micelles with ROS-responsiveness. [20][21][22][23][24] However, current designs always allow the micelles to exhibit responsive drug delivery at relatively high concentrations of ROS, which is the main obstacle to limit their further uses. Therefore, it is highly pressing to improve the sensitivity of the ROS-responsive polymeric nanocarriers.Zhu and co-workers reported a cinnamaldehyde-encapsulated nanomicellar system based on H 2 O 2 -responsive hyperbranched polyglycerols with thioether-linked anticancer drug of 7-ethyl-10-hydroxy-camptothecin (SN38). [25] The in vitro study proposed that the preferentially released cinnamaldehyde (CA) could effectively induce intracellular ROS generation and accelerate the micellar degradation to release SN38 for an enhanced cancer therapy. Ge and co-workers fabricated a novel ROS-responsive polyprodrug polymersome loaded with ultrasmall iron oxide nanoparticles and glucose oxidase. The tumor acidity-activable Fenton reaction can efficiently produce ·OH to trigger camptothecin (CPT) release for high-efficient cooperative cancer therapy. [26] Such strategies involve locally catalyzingtriggered chemical reactions to generate abundant and special products only inside tumor tissues and therefore provide a highly efficient tumor-specific theranostic effects. Cancer tissues are usually featured with mild acidic conditions and high ROS levels due to the fast metabolism-induced overproduction of metabolic products. [17][18][19][20][21][22][23][24][25][26][27][28][29] In addition, the concentration of Cu(II) ions in cancer cells is 2-3 times higher than that within normal cells (0.98 µg mL −1 ), while the concentrations of Zn(II), Fe(III), and Se(II) are significantly lower in cancer tissues. [30] It should be noted that a Fenton-like reaction may occur for the polyphenols and Cu(II) complexed system to quickly generate a variety of reactive oxygen species. [31] Therefore, cancer tissues are more subject to electron transfer between Cu(II) ions and polyphenols to generate ROS. Such Cu-complexed Fenton-like reaction can also effectively induce the tumor-specific therapy Compared to normal cells, there is a relatively high level of reactive oxygen species (ROS) in tumor cells caused by defecting ROS scavenging systems. To this issue, developing ROS-responsive nanocarriers has been a promising way to cancer therapy. However, it is always difficult for a certain ROSresponsive nanocarrier to be perfectly triggered due to the complexity of cancerous tissue...

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Section: Resultsmentioning

confidence: 99%

Iminoboronate Backbone‐Based Hyperbranched Polymeric Micelles with Fenton‐Like Enhanced ROS Response

Zhang

Guo

Liu

et al. 2020

Macro Chemistry & Physics

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“…The antitumor activities in vivo assay were performed as described previously with minor modifications [12,[22][23][24]. C57BL/6J mice (20 ± 2 g) for the xenograft animal model were purchased from the Laboratory Animal Center of Jilin University (Jilin, China).…”

Section: In Vitro and In Vivo Antitumor Activitiesmentioning

confidence: 99%

A Novel Betulinic Acid Analogue: Synthesis, Solubility, Antitumor Activity and Pharmacokinetic Study in Rats

Liang

Zhu

et al. 2023

Molecules

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Betulinic acid (BA) and betulin (BE) are naturally pentacyclic triterpenes with documented biological activities, especially antitumor and anti-inflammatory activity. However, their bioavailability in vivo is not satisfactory in terms of medical applications. Thus, to improve the solubility and bioavailability so as to improve the efficacy, 28-O-succinyl betulin (SBE), a succinyl derivative of BE, was synthesized and its solubility, in vitro and in vivo anti-tumor activities, the apoptosis pathway as well as the pharmacokinetic properties were investigated. The results showed that SBE exhibited significantly higher solubility in most of the tested solvents, and showed a maximum solubility of 7.19 ± 0.66 g/L in n-butanol. In vitro and in vivo anti-tumor activity assays indicated both BA and SBE exhibited good anti-tumor activities, and SBE demonstrated better potential compared to BA. An increase in the ratio of Bad/Bcl-xL and activation of caspase 9 was found in SBE treated Hela cells, suggesting that the intrinsic mitochondrial pathway is involved in SBE induced apoptosis. Compared with BA, SBE showed much-improved absorption and bioavailability in pharmacokinetic studies.

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The recent developments of camptothecin and its derivatives as potential anti-tumor agents

Wang

Zhuang

Wang

et al. 2023

European Journal of Medicinal Chemistry

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Synthesis, antitumor activity and pharmacokinetic study of 10‐propionyloxy camptothecin in rats

Cited by 3 publications

References 16 publications

Iminoboronate Backbone‐Based Hyperbranched Polymeric Micelles with Fenton‐Like Enhanced ROS Response

Iminoboronate Backbone‐Based Hyperbranched Polymeric Micelles with Fenton‐Like Enhanced ROS Response

A Novel Betulinic Acid Analogue: Synthesis, Solubility, Antitumor Activity and Pharmacokinetic Study in Rats

The recent developments of camptothecin and its derivatives as potential anti-tumor agents

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