ArticleOncotarget2015
A novel orally active water-soluble inhibitor of human glutathione transferase exerts a potent and selective antitumor activity against human melanoma xenografts.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Ultrastructural studies distinguish skin diversities among Galápagos iguanas.Biology direct · 2025Article
- Overexpression of Glutathione S-Transferases in Human Diseases: Drug Targets and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2023Review
- NBDHEX re-sensitizes adriamycin-resistant breast cancer by inhibiting glutathione S-transferase pi.Cancer medicine · 2023Article
- The Nitrobenzoxadiazole Derivative NBDHEX Behaves asPharmaceuticals (Basel, Switzerland) · 2022Article
- Oxidative Stress-Related Mechanisms in Melanoma and in the Acquired Resistance to Targeted Therapies.Antioxidants (Basel, Switzerland) · 2021Review
- Anti-influenza A virus activity and structure-activity relationship of a series of nitrobenzoxadiazole derivatives.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Glutathione S-Transferases in Cancer.Antioxidants (Basel, Switzerland) · 2021Review
- Synthesis and characterisation of a new benzamide-containing nitrobenzoxadiazole as a GSTP1-1 inhibitor endowed with high stability to metabolic hydrolysis.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol: a promising new anticancer compound.Bioscience reports · 2018Review
- Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases.Oncogenesis · 2018Review
- GlutathioneDrug design, development and therapy · 2018Review
- A new nitrobenzoxadiazole-based GSTP1-1 inhibitor with a previously unheard of mechanism of action and high stability.Journal of enzyme inhibition and medicinal chemistry · 2017Article
- Article
- c-Jun N-terminal kinase activation by nitrobenzoxadiazoles leads to late-stage autophagy inhibition.Journal of translational medicine · 2016Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We designed and synthesized two novel nitrobenzoxadiazole (NBD) analogues of the anticancer agent 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (NBDHEX). The new compounds, namely MC3165 and MC3181, bear one and two oxygen atoms within the hydroxy-containing alkyl chain at the C4 position of the NBD scaffold, respectively. This insertion did not alter the chemical reactivity with reduced glutathione, while it conferred a remarkable increase in water solubility. MC3181 was more selective than NBDHEX towards the target protein, glutathione transferase P1-1, and highly effective in vitro against a panel of human melanoma cell lines, with IC50 in the submicromolar-low micromolar range. Interestingly, the cellular response to MC3181 was cell-type-specific; the compound triggered a JNK-dependent apoptosis in the BRAF-V600E-mutated A375 cells, while it induced morphological changes together with an increase in melanogenesis in BRAF wild-type SK23-MEL cells. MC3181 exhibited a remarkable therapeutic activity against BRAF-V600E-mutant xenografts, both after intravenous and oral administration. Outstandingly, no treatment-related signs of toxicity were observed both in healthy and tumor-bearing mice after single and repeated administrations. Taken together, these results indicate that MC3181 may represent a potential novel therapeutic opportunity for BRAF-mutated human melanoma, while being safe and water-soluble and thus overcoming all the critical aspects of NBDHEX in vivo.
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