Assessment of the chemotherapeutic potential of a new camptothecin derivative, ZBH-1205.

  title={Assessment of the chemotherapeutic potential of a new camptothecin derivative, ZBH-1205.},
  author={Di Wu and Weiguo Shi and Jing Zhao and Zhengren Wei and Zhijiao Chen and Dawei Zhao and Shijie Lan and Jiandong Tai and Bohua Zhong and Hong Yu},
  journal={Archives of biochemistry and biophysics},
CPT-11 (irinotecan) is a derivative of camptothecin which is a natural product derived from the Chinese tree Camptotheca acuminta and widely used in antitumor therapy. Here, the in vitro anti-tumor activity and associated mechanisms of a novel derivative of camptothecin, ZBH-1205, were investigated in a panel of 9 human tumor cell lines, as well as in HEK 293 and SK-OV-3/DPP, a multi-drug resistant (MDR) cell line, and compared to CPT-11 and 7-ethyl-10-hydroxy-camptothecin (SN38). Comparisons… Expand
Antitumor potential of a novel camptothecin derivative, ZBH-ZM-06.
ZBH-ZM-06 had higher antitumor activity than CPT-11 and SN38, which was shown by its release of the effective ingredient; growth inhibition of a broad spectrum of tumor cells; inhibition of DNA topoisomerase (Topo-1); and promotion of apoptosis through an intrinsic signaling pathway. Expand
Antimicrobial, antioxidant and cytotoxic evaluation of diazenyl chalcones along with insights to mechanism of interaction by molecular docking studies
These diazenyl chalcones scaffolds have shown their potential as lead for future expansion of novel antimicrobial and cytotoxic drugs and affirmed their safety by presenting less cytotoxicity towards HEK cells. Expand
Irinotecan: 25 years of cancer treatment.
  • C. Bailly
  • Biology, Medicine
  • Pharmacological research
  • 2019
This review highlights recent discoveries in the field of IRT and its derivatives, including analogues of the active metabolite SN38 (such as FL118), the recently approved liposomal form Nal-IRI and SN38-based immuno-conjugates currently in development ( such as sacituzumab govitecan). Expand
Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: did we miss something in CPT analogue molecular targets for treating human disease such as cancer?
It is argued that new CPT Top1 inhibitor drugs are unlikely being found to be significantly better than irinotecan and/or topOTecan in terms of the overall antitumor activity and toxicity, and it is provided evidence that certain CPT analogues can exert improved efficacy with low toxicity independently of topoisomerase I (Top1) inhibition. Expand
Nrf2 Down-Regulation by Camptothecin Favors Inhibiting Invasion, Metastasis and Angiogenesis in Hepatocellular Carcinoma
  • Qian Liu, Shanshan Zhao, +5 authors Feng Chen
  • Medicine
  • Frontiers in Oncology
  • 2021
Down-regulation of Nrf2 demonstrated inhibition of invasion, metastasis, and angiogenesis of hepatoma, which may provide a potential therapy in HCC. Expand


Genz-644282, a Novel Non-Camptothecin Topoisomerase I Inhibitor for Cancer Treatment
Genz-644282 has superior or equal antitumor activity in the human tumor xenografts than the standard drug comparators and is currently undergoing phase 1 clinical trial. Expand
Differential stabilization of eukaryotic DNA topoisomerase I cleavable complexes by camptothecin derivatives.
Cleavable complexes induced by SN-38 and 10,11-methylenedioxycamptothecin were markedly more stable (less rapidly reversible) than those induced by CPT, topotecan, and 9-aminocamptothecins, indicating that both the 10-hydroxy and the 7-ethyl group ofSN-38 probably interact with the drug binding site of top1-cleavable complex. Expand
Novel Stable Camptothecin Derivatives Replacing the E-Ring Lactone by a Ketone Function Are Potent Inhibitors of Topoisomerase I and Promising Antitumor Drugs
The cytotoxicity of S38809 and its ability to stabilize cleavable complexes was considerably reduced in camptothecin-resistant cells that express a mutated topo 1, confirming that topo1 is its primary target. Expand
Anticancer effect of SN-38 on colon cancer cell lines with different metastatic potential.
The effect of SN-38 on the colon cancer cell lines was mediated via conducting S-phase and G2 arrest and apoptosis, indicating thatSN-38 can be used to treat advanced colon cancers. Expand
Topoisomerase degradation, DSB repair, p53 and IAPs in cancer cell resistance to camptothecin-like topoisomerase I inhibitors.
The role of p53 and inhibitors of apoptosis proteins (IAPs), particularly XIAP and survivin, in cancer cell resistance to CPT-like chemotherapeutics is highlighted. Expand
Identification of a new metabolite of CPT-11 (irinotecan): pharmacological properties and activation to SN-38.
The structure of CPT-11, a water-soluble derivative of camptothecine with promising activity against several types of malignancies, is postulated to be 7-ethyl-10-(4-amino-1-piperidino)carbonyloxycamptotheCine, and this structure was synthesized by Rhône-Poulenc Rorer. Expand
Topoisomerase I inhibitors: camptothecins and beyond
  • Y. Pommier
  • Biology, Medicine
  • Nature Reviews Cancer
  • 2006
The mechanisms and molecular determinants of tumour response to TOP1 inhibitor are reviewed, and rational combinations of TOP1 inhibitors with other drugs are considered based on current knowledge of repair and checkpoint pathways that are associated with TOP1-mediated DNA damage. Expand
A novel DNA topoisomerase I inhibitor with different mechanism from camptothecin induces G2/M phase cell cycle arrest to K562 cells.
Biochemical Top1 assays indicate that CY13II exhibits a different inhibitory mechanism from camptothecin, which specifically inhibits the catalytic cleavage activity of Top1 instead of forming the drug-enzyme-DNA covalent ternary complex. Expand
STK295900, a Dual Inhibitor of Topoisomerase 1 and 2, Induces G2 Arrest in the Absence of DNA Damage
STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells, suggesting that it has a potential to be developed as an anticancer chemotherapeutic agent. Expand
Synthesis and Biological Evaluation of Novel 10-Substituted-7-ethyl-10-hydroxycamptothecin (SN-38) Prodrugs
Novel prodrugs prepared by conjugating amino acids or dipeptides to the 10-hydroxyl group of SN-38 via a carbamate linkage exhibited the same level of tumor growth inhibitory activity as irinotecan (CPT-11) in a human colon xenograft model in vivo. Expand