Phosphate ester derivatives of homocamptothecin: Synthesis, solution stabilities and antitumor activities

Miao, Zhenyuan; Zhang, Jing; Liang, You; Wang, Juan; Sheng, Chunquan; Yao, Jiangzhong; Zhang, Wannian; Feng, Hao; Guo, Wei; Zhou, Lei; Liu, Wenfeng; Zhu, Lin; Cheng, Pengfei; Che, Xiaoying; Wang, Wenya; Luo, Chi-Wen; Xu, Yulan; Dong, Guoqiang

doi:10.1016/j.bmc.2010.03.039

Cited by 19 publications

(11 citation statements)

References 7 publications

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“…From an SAR viewpoint, the cytotoxicity of the phosphodiesters was lower than that of the phosphotriesters and the length of the phosphate alkyl chain affected the potency. Compound 146 with dibutyl phosphate group showed greater tumor‐inhibitory activity than CPT‐11 ( 4 ) in an A549 xenograft model, potent activity in a DNA cleavage assay at a concentration of 100 μM, and good stability at both pH 7.4 and 3.0 …”

Section: Biological Activity Of Cpt and Related Derivativesmentioning

confidence: 99%

“…The high cytotoxicity of hCPT derivatives prompted Zhang et al to investigate a series of water‐soluble 10‐phosphate esters. Most of the resulting compounds displayed moderate cytotoxicity against three tested cell lines ( 142 – 149 , Table ).…”

Section: Biological Activity Of Cpt and Related Derivativesmentioning

confidence: 99%

“…From the results shown in Table VII, several hCPT compounds with an alkenyl or an (alkoxycarbonyl)ethenyl group exhibited good cytotoxic activity comparable or superior to 3 against A-549 cancer cells. 75 The high cytotoxicity of hCPT derivatives prompted Zhang et al 76 to investigate a series of water-soluble 10-phosphate esters. Most of the resulting compounds displayed moderate cytotoxicity against three tested cell lines (142-149, Table VIII).…”

Section: A B and E Ring Modified Cpt Analogsmentioning

confidence: 99%

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Perspectives on Biologically Active Camptothecin Derivatives

et al. 2015

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Camptothecins (CPTs) are cytotoxic natural alkaloids that specifically target DNA topoisomerase I. Research on CPTs has undergone a significant evolution from the initial discovery of CPT in the late 1960s through the study of synthetic small molecule derivatives to investigation of macromolecular constructs and formulations. Over the past years, intensive medicinal chemistry efforts have generated numerous CPT derivatives. Three derivatives, topotecan, irinotecan, and belotecan, are currently prescribed as anticancer drugs, and several related compounds are now in clinical trials. Interest in other biological effects, besides anticancer activity, of CPTs is also growing exponentially, as indicated by the large number of publications on the subject during the last decades. Therefore, the main focus of the present review is to provide an ample but condensed overview on various biological activities of CPT derivatives, in addition to continued up-to-date coverage of anticancer effects.

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Section: Biological Activity Of Cpt and Related Derivativesmentioning

confidence: 99%

Section: Biological Activity Of Cpt and Related Derivativesmentioning

confidence: 99%

Section: A B and E Ring Modified Cpt Analogsmentioning

confidence: 99%

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Perspectives on Biologically Active Camptothecin Derivatives

et al. 2015

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“…Phosphorus oxychloride is a liquid phosphorylating reagent utilized in the synthesis of phosphate esters and cross-linked starch and cellulose because of its high solubility in organic solvents. 32–36 Furthermore, negligible self-reaction should prevent the formation of polyphosphates, making it a promising alternative to P 2 O 5 . Herein, we report the selective monophosphorylation of chitosan using POCl 3 in methanesulfonic acid to produce a water-soluble product of high molecular weight.…”

Section: Introductionmentioning

confidence: 99%

Selective monophosphorylation of chitosan via phosphorus oxychloride

Suchyta

Soto

2017

Polym. Chem.

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Chitosan was selectively monophosphorylated via reaction with phosphorus oxychloride (POCl3) to enhance water solubility while avoiding polyphosphate formation. The use of POCl3 resulted in negligible product degradation (i.e., breakdown of O-glycosidic bonds) even after a 3 d reaction period (<5% weight loss). X-ray photoelectron spectroscopy (XPS) characterization of the POCl3-phosphorylated chitosan (P-chitosan) revealed a phosphorus to nitrogen (P/N) atomic ratio of 0.30. Phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy verified the monophosphorylation of chitosan’s primary and secondary alcohols, and primary amines. The calcium chelation efficiency for the phosphorylated product approached 0.05 mg Ca2+ per mg of P-chitosan as measured by inductively coupled plasma-optical emission spectrometry (ICP-OES), indicating improved chelation over native chitosan. This selective monophosphorylation approach proved useful for modifying other biopolymers, including cellulose and alginate.

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“…Topoisomerase I activity was detected as described by Miao et al [6] . All reactions were carried out in 20-l volumes (16 l double-distilled water, 2 l DNA topoisomerase I buffer, and 2 l 0.1% bovine serum albumin) containing 0.25 g supercoiled DNA, 0.5 U topoisomerase I with or without drug.…”

Section: Dna Topoisomerase I Activity Assaysmentioning

confidence: 99%

Camptothecin Fails to Induce Apoptosis in Tumor Necrosis Factor-Alpha-Treated HaCaT Cells

Sun¹,

Han²,

Li³

et al. 2012

Pharmacology

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Camptothecin (CPT), a DNA topoisomerase I inhibitor, was originally isolated from the fruits of the Chinese Camptotheca acuminata tree. CPT and its derivatives have been used in the treatment of psoriasis and cancer in China for decades. It is well known that tumor necrosis factor-α (TNF-α) is a key proinflammatory cytokine in the pathogenesis of psoriasis. In this study, we investigated the effect of CPT on TNF-α-treated HaCaT cells. The results indicated that CPT in the concentration range of 0.5–2.0 µg·ml^–1 failed to show any proapoptotic effect in HaCaT cells. It was found that both CPT and TNF-α up-regulated the expression of TRAIL receptor 1/2 but not TRAIL in HaCaT cells. Furthermore, the expression of antiapoptotic proteins (IAP1, IAP2, and Bcl-X_L) was up-regulated by TNF-α and suppressed by CPT in HaCaT cells. Because these gene products are known to be regulated by nuclear factor-kappa B (NF-ĸB), we examined the role of CPT on NF-ĸB activation. It was found that CPT not only failed to inhibit TNF-α-induced NF-ĸB activation but also contributed to NF-ĸB activation. In addition to these effects, CPT also promoted the production of interleukin-6, similar to TNF-α, in HaCaT cells. In conclusion, despite ample evidence supporting CPT-induced carcinoma cell apoptosis, our study clearly shows that CPT fails to show any proapoptotic effects in HaCaT cells, even though it enhanced TRAIL receptor 1/2 expression and inhibited the expression of TNF-α-induced antiapoptotic proteins. Taken together, this study demonstrates that CPT fails to block the activity of TNF-α. With respect to the NF-ĸB-activating role of CPT, we suggest that the benefit of CPT in the treatment of psoriasis should be reevaluated.

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Phosphate ester derivatives of homocamptothecin: Synthesis, solution stabilities and antitumor activities

Cited by 19 publications

References 7 publications

Perspectives on Biologically Active Camptothecin Derivatives

Perspectives on Biologically Active Camptothecin Derivatives

Selective monophosphorylation of chitosan via phosphorus oxychloride

Camptothecin Fails to Induce Apoptosis in Tumor Necrosis Factor-Alpha-Treated HaCaT Cells

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