Current status of CPT and its analogues in the treatment of malignancies

Hu, Guohua; Zekria, David; Cai, Xueli; Ni, Xiaoling

doi:10.1007/s11101-015-9397-1

Cited by 10 publications

(7 citation statements)

References 120 publications

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“…Another class of therapeutic agents acting at a nuclear level are topoisomerase I inhibitors [ 8 , 9 ]. Topoisomerases relieve the torsional stress associated with the separation of DNA strands during transcription and DNA replication.…”

Section: Introductionmentioning

confidence: 99%

Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents

Cincinelli

Musso

Artali³

et al. 2018

PLoS ONE

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Recent studies have shown that HDAC inhibitors act synergistically with camptothecin derivatives in combination therapies. To exploit this synergy, new hybrid molecules targeting simultaneously topoisomerase I and HDAC were designed. In particular, a selected multivalent agent containing a camptothecin and a SAHA-like template showed a broad spectrum of antiproliferative activity, with IC50 values in the nanomolar range. Preliminary in vivo results indicated a strong antitumor activity on human mesothelioma primary cell line MM473 orthotopically xenografted in CD-1 nude mice and very high tolerability.

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Section: Introductionmentioning

confidence: 99%

Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents

Cincinelli

Musso

Artali³

et al. 2018

PLoS ONE

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“…Furthermore, edible macrophytes have long been a valuable source of traditional medicine, and freshwater macrophytes exhibit anticancer and antioxidant properties ( 14 ). Camptothecin, a terpene indole alkaloid isolated from the Camptotheca acuminate , demonstrated anti-tumor potential and was eventually licensed by the FDA for various types of cancer ( 15 ). Another phytochemical, luteolin ( 16 ), was approved for the inhibition of chronic inflammation, while quercetin ( 17 ) demonstrated strong anti-inflammatory properties.…”

Section: Introductionmentioning

confidence: 99%

phytochemdb: a platform for virtual screening and computer-aided drug designing

et al. 2022

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The phytochemicals of medicinal plants are regarded as a rich source of diverse chemical spaces that have been used as supplements and alternative medicines in the millennium. Even in this era of combinatorial chemical drugs, phytomedicines account for a large share of the statistics of newly approved drugs. In the field of computational aided and rational drug design, there is an urgent need to develop and build a useful phytochemical database management system with a user-friendly interface that allows proper data storage, retrieval and management. We showed ‘phytochemdb’, a manually managed database that compiles 525 plants and their corresponding 8093 phytochemicals, aiming to incorporate the activities of phytochemicals from medicinal plants. The database collects molecular formula, three-dimensional/two-dimensional structure, canonical SMILES, molecular weight, no. of heavy atoms, no. of aromatic heavy atoms, fraction Csp3, no. of rotatable bonds, no. of H-bond acceptors, no. of H-bond donors, molar refractivity, topological polar surface area, gastrointestinal absorption, Blood–Brain Barrier (BBB) permeant, P-gp substrate, CYP1A2 inhibitor, CYP2C19 inhibitor, CYP2C9 inhibitor, CYP2D6 inhibitor, CYP3A4 inhibitor, Log Kp, Ghose, Veber, Egan, Muegge, bioavailability scores, pan-assay interference compounds, Brenk, Leadlikeness, synthetic accessibility, iLOGP and Lipinski rule of five with the number of violations for each compound. It provides open contribution functions for the researchers who screen phytochemicals in the laboratory and have released their data. ‘phytochemdb’ is a comprehensive database that gathers most of the information about medicinal plants in one platform, which is considered to be very beneficial to the work of researchers on medicinal plants. ‘phytochemdb’ is available for free at https://phytochemdb.com/.

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“…Camptothecin and its derivatives are commonly used to treat breast and ovarian cancer. Topotecan is commonly used to treat ovarian and lung cancer [4], and irinotecan (CPT-11) is used in combination with 5-fluorouracil to treat colorectal cancer [5]. Unfortunately, the safety of these compounds is compromised by either their own toxicity or the toxicity of their active metabolites.…”

Section: Introductionmentioning

confidence: 99%

Effect of Pterostilbene, a Natural Derivative of Resveratrol, in the Treatment of Colorectal Cancer through Top1/Tdp1-Mediated DNA Repair Pathway

Zhang

Liu

Sun

et al. 2021

Cancers

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Topoisomerase 1 (Top1) inhibitor is an effective anticancer drug, but several factors limit its clinical application such as drug inactivation, tyrosyl-DNA phosphodiesterase 1 (Tdp1)-mediated tumor drug resistance, and its toxicity. Our previous study identified pterostilbene (PTE) and resveratrol (RE) to suppress these two proteins by binding to their active center. PTE and RE could inhibit the proliferation of various colorectal cancer cells, induce cell apoptosis, and make cell cycle stay in G2/M phase in vitro. PTE and RE could decrease Top1 and Tdp1 contents and mRNA expression in wild-type, constructed Tdp1 overexpressing CL187, Top1- or Tdp1- silenced CL187 cell lines. PTE exhibited excellent antitumor activity in subcutaneous CL187 transplantation model (TGI = 79.14 ± 2.85%, 200 mg/kg, i.p.) and orthotopic transplantation model (TGI = 76.57 ± 6.34%, 100 mg/kg, i.p.; TGI = 72.79 ± 4.06%, 500 mg/kg, i.g.) without significant toxicity. PTE had no significant inhibitory effect on non-tumor cell proliferation in vitro and would not induce damage to liver, kidney, and other major organs. Overall, PTE and RE can inhibit the activity of Top1 enzyme and inhibit the DNA damage repair pathway mediated by Top1/Tdp1, and can effectively inhibit colorectal cancer development with low toxicity, thus they have great potential to be developed into a new generation of anti-tumor drugs.

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Current status of CPT and its analogues in the treatment of malignancies

Cited by 10 publications

References 120 publications

Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents

Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents

phytochemdb: a platform for virtual screening and computer-aided drug designing

Effect of Pterostilbene, a Natural Derivative of Resveratrol, in the Treatment of Colorectal Cancer through Top1/Tdp1-Mediated DNA Repair Pathway

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