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- W4281627076 abstract "Abstract For the first time, compounds developed from the 1,2,3‐triazole scaffold were evaluated as novel drugs to treat triple‐negative breast cancer (TNBC). Four organic salts were idealized as nonclassical bioisosteres of miltefosine, which is used in the topical treatment for skin metastasizing breast carcinoma. Among them, derivative dhmtAc displayed better solubility and higher cytotoxicity against the human breast adenocarcinoma cell line and mouse 4T1 cell lines, which are representatives of TNBC. In vitro assays revealed that dhmtAc interferes with cell integrity, confirmed by lactate dehydogenase leakage. Due to its human peripheral blood mononuclear cell (PBMC) toxicity, dhmtAc in vivo studies were carried out with the drug incorporated in a long‐circulating and pH‐sensitive liposome (SpHL‐dhmtAc), and the acute toxicity in BALB/c mice was determined. Free dhmtAc displayed cardiac and pulmonary toxicity after the systemic administration of 5 mg/kg doses. On the other hand, SpHL‐dhmtAc displayed no toxicity at 20 mg/kg. The in vivo antitumor effect of SpHL‐dhmtAc was investigated using the 4T1 heterotopic murine model. Intravenous administration of SpHL‐dhmtAc reduced the tumor volume and weight, without interfering with the body weight, compared with the control group and the dhmtAc free form. The incorporation of the triazole compound in the liposome allowed the demonstration of its anticancer potential. These findings evidenced 1,3,4‐trisubstituted‐1,2,3‐triazole as a promising scaffold for the development of novel drugs with applicability for the treatment of patients with TNBC." @default.
- W4281627076 created "2022-06-13" @default.
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- W4281627076 date "2022-05-27" @default.
- W4281627076 modified "2023-10-10" @default.
- W4281627076 title "Acute toxicity and antitumor potential of 1,3,4‐trisubstituted‐1,2,3‐triazole dhmtAc‐loaded liposomes on a triple‐negative breast cancer model" @default.
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- W4281627076 doi "https://doi.org/10.1002/ardp.202200004" @default.
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