Synthesis and antitumor activity of novel substituted uracil-1′(N)-acetic acid ester derivatives of 20(S)-camptothecins

Li, Dizao; Zhang, Qiang-Zhe; Wang, Cun-ying; Zhang, Yanling; Li, Xingyu; Huang, Jitao; Liu, Hongyan; Fu, Zhang; Song, Hua-Xian; Lin, Jian; Ji, Tengfei; Pan, Xiaohong

doi:10.1016/j.ejmech.2016.11.013

Cited by 26 publications

(7 citation statements)

References 33 publications

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“…Similar to Camptothecin, hybrid 68b was also found to inhibit topoisomerase-1 more efficiently (Li et al, 2017). Hence, hybrid 68b with high potency and lower toxicity can be developed as a potential drug candidate in future.…”

Section: Uracil-camptothecin Hybridsmentioning

confidence: 99%

Recent advancements in Uracil and 5-Fluorouracil hybrids as potential anticancer agents: A review

2020

J app pharm sci

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Cancer is the most dreadful disease and the second main cause of death worldwide. The continuous developments have been going on in order to design potent molecules such that this leading cause of death can be dealt with. In order to decrease the level of toxicity and to improve the selectivity of drugs toward cancer targets, the development of hybrid molecules has become the center of research, and scientists are doing timeless efforts to generate such a hybrid which has got no comparison with the previous developments. The heterocyclic moiety Uracil and many of its derivatives were already exposed as promising anticancer agents. Moreover, coupling of Uracil and 5-Fluorouracil (5-FU) with different pharmacophores has been proven to be an excellent strategy against cancer. Hence, the present review is an effort to collectively represent all the earlier and recent developments of Uracil and 5-FU hybrids reported to have a significant anticancer profile. Expectantly, we can assure that this article can serve as the basis for further developments in Uracil and 5-FU hybrids and will surely motivate the medicinal chemists for producing unique anticancer drug.

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Section: Uracil-camptothecin Hybridsmentioning

confidence: 99%

Recent advancements in Uracil and 5-Fluorouracil hybrids as potential anticancer agents: A review

2020

J app pharm sci

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“…By the end of 2017, the cumulative sales of irinotecan and topotecan had reached 15 billion US dollars [7]. Importantly, in addition to CPT derivatives with artificial modifications [8,9], natural CPT analogues such as 10-hydroxycamptothecin (10HCPT) and 9-methoxycamptothecin (9MCPT) found in C. acuminata, Nothapodytes nimmoniana (J. Graham) Mabberley (Icacinaceae), and other plants also display good anti-cancer activity and can be used for developing new cancer drugs with improved efficacy [10,11].…”

Section: Phytochemical Analysis Of Nothapodytes Tomentosa and Distrib...mentioning

confidence: 99%

“…However, the growing demand for CPT in the global pharmaceutical industry has caused a severe shortage of CPT-producing plant resources. In this study, phytochemical analysis of Nothapodytes tomentosa results in the isolation and identification of CPT (13) and 16 analogues (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(14)(15)(16)(17), including a new (1) and five known (9, 10, 12, 15, and 17) CPT analogues with an open E-ring. In view of the potential anticancer activity of CPT analogues with an open E-ring, the fragmentation pathways and mass spectra profiles of these six CPT analogues (1, 9, 10, 12, 15, and 17) are investigated, providing a reference for the rapid detection of these compounds in other plants.…”

Section: Introductionmentioning

confidence: 99%

Phytochemical Analysis of Nothapodytes tomentosa and Distribution and Content of Camptothecin and its Analogues in Four Plants

Chen

et al. 2023

Planta Med

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Camptothecin (CPT) and its derivatives have attracted worldwide attention due to their notable anticancer activity. However, the growing demand for CPT in the global pharmaceutical industry has caused a severe shortage of CPT-producing plant resources. In this study, phytochemical analysis of Nothapodytes tomentosa resulted in the isolation and identification of CPT (13) and 16 analogues (1-12, 14-17), including a new (1) and five known (9, 10, 12, 15 and 17) CPT analogues with an open E-ring. In view of the potential anticancer activity of CPT analogues with an open E-ring, the fragmentation pathways and mass spectra profiles of these six CPT analogues (1, 9, 10, 12, 15 and 17) were investigated, providing a reference for the rapid detection of these compounds in other plants. Furthermore, based on the fragmentation patterns of CPT (13) and known analogues (2-8, 11, 14, 16, 18-26), the distribution and content of these compounds in different tissues of N. tomentosa, N. nimmoniana, Camptotheca acuminata, and Ophiorrhiza japonica were further studied. Our findings not only provide an alternative plant resource for further expanding the development and utilization of CPT and its analogues, but also lay a foundation for improving the utilization of known CPT-producing plant resources.

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“…The reaction was 9.28, 27.43, 30.75, 50.69, 55.38, 65.71, 72.84, 97.16, 119.59, 119.68, 126.55, 128.79, 130.86, 131.64, 145.81, 146.33, 149.53, 150.47, 152.99, 157.26, 172.91, 173.10 The in vivo antitumor studies were performed following the method described previously with minor modifications (Cao et al, 2016;Cui et al, 2016;Li et al, 2017;Wang, Huang, Sun, & Pan, 2015). Then 60 μL of propionic anhydride was added dropwise.…”

Section: Synthesis Of Pcptmentioning

confidence: 99%

“…These data revealed that the concentration of the active metabolite HCPT was much higher than that of PCPT in vivo. As shown in Figure 7, the concentration of PCPT 9.28, 27.43, 30.75, 50.69, 55.38, 65.71, 72.84, 97.16, 119.59, 119.68, 126.55, 128.79, 130.86, 131.64, 145.81, 146.33, 149.53, 150.47, 152.99, 157.26, 172.91, 173.10 The in vivo antitumor studies were performed following the method described previously with minor modifications (Cao et al, 2016;Cui et al, 2016;Li et al, 2017;Wang, Huang, Sun, & Pan, 2015). C57BL/6 J mice (20 ± 2 g) obtained from the Laboratory Animal Mice were divided into four groups (n = 6) randomly on the next day after implantation.…”

Section: Pharmacokinetic Studymentioning

confidence: 99%

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

Zheng

Shao

Fan

et al. 2018

Biomedical Chromatography

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In the present study, a 10-position modified of camptothecin, 10-propionyloxy camptothecin (PCPT) was esterified from 10-hydroxcamptothecin (HCPT), which could metabolize to HCPT in vivo. PCPT displayed a relatively stronger antitumor activity in vitro and in vivo. Thereafter a simple, sensitive and rapid HPLC method coupled with a fluorescence detector was developed and validated for the assay of PCPT and its active metabolite HCPT in rat plasma. The method was validated for accuracy, precision, linearity, selectivity and recovery. The validated method was successfully applied to the pharmacokinetic study of PCPT in rats after intravenous administration. The results showed that PCPT could be mainly converted to HCPT in plasma with the AUC value of 3.69 ± 4.44 and 311.16 ± 188.81 ng h/mL for PCPT and HCPT, respectively.

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Synthesis and antitumor activity of novel substituted uracil-1′(N)-acetic acid ester derivatives of 20(S)-camptothecins

Cited by 26 publications

References 33 publications

Recent advancements in Uracil and 5-Fluorouracil hybrids as potential anticancer agents: A review

Recent advancements in Uracil and 5-Fluorouracil hybrids as potential anticancer agents: A review

Phytochemical Analysis of Nothapodytes tomentosa and Distribution and Content of Camptothecin and its Analogues in Four Plants

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

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