ArticleDalton transactions (Cambridge, England : 2003)2020
Oxamusplatin: a cytotoxic Pt(ii) complex of a nitrogen mustard with resistance to thiol based sequestration displays enhanced selectivity towards cancer.
Article in Dalton transactions (Cambridge, England : 2003), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 18 citations in OpenAlex.
- Square-Planar vs. Trigonal Bipyramidal Geometry in Pt(II) Complexes Containing Triazole-Based Glucose Ligands as Potential Anticancer Agents.International journal of molecular sciences · 2021Article
- Targeting critical pathways in ferroptosis and enhancing antitumor therapy of Platinum drugs for colorectal cancer.Science progressReview
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5 authors at 1 institution in 1 country.
Funding
Abstract
Pt(ii) drugs and nitrogen mustards show severe side effects, poor tumour selectivity and face growing resistance by cancer cells due to sequestration by thiol-containing molecules (viz. glutathione (GSH) and copper ATPases like ATP7A/7B). ATP7A and ATP7B-sequestered Pt(ii) complexes show dose inefficacy and resistance. The incorporation of bulky ligands and chelating leaving groups may prevent deactivation by thiols. In this work, we have synthesised four new Pt(ii) complexes (3-6) of two carrier ligands, bis(2-hydroxyethyl)pyridylmethylamine (L1) and bis(2-chloroethyl)pyridylmethylamine (L2) with oxalato and cyclobutanedicarboxylato leaving groups. Among these four new complexes, the Pt(ii) complex of L2 with the oxalato leaving group (5, termed "oxamusplatin") is cytotoxic. Oxamusplatin is more resistant than cisplatin or oxaliplatin towards hydrolysis, thiol binding and sequestration by ATP7B. It targets cellular DNA and is capable of disrupting the microtubule network in the cytoskeleton. Oxamusplatin demonstrates better selectivity than oxaliplatin towards cancerous cells. It is ca. 4-10 times more cytotoxic towards metastatic prostate carcinoma (DU-145, IC50 = 21 ± 1 μM) and ca. 10-24 times more cytotoxic towards breast adenocarcinoma (MCF-7, IC50 = 8.1 ± 0.8 μM) compared to the three noncancerous cells investigated.
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