Synthesis and anticancer activity of tertiary amides of salinomycin and their C20-oxo analogs.

Synthesis and anticancer activity of tertiary amides of salinomycin and their C20-oxo analogs. ChemMedChem. 2019 Nov 08;: Authors: Czerwonka D, Urbaniak A, Sobczak S, Piña-Oviedo S, Chambers TC, Antoszczak M, Huczyński A Abstract The polyether ionophore salinomycin (SAL) has captured much interest because of its potent activity against cancer cells and cancer stem cells. Our previous studies have indicated that C1/C20 double-modification of SAL is a useful strategy to generate diverse agents with promising biological activity profiles. Thus, in this paper, we describe the synthesis of a new class of SAL analogs that combine key modifications at the C1 and C20 positions. The activity of the obtained SAL derivatives was evaluated using primary acute lymphoblastic leukemia, human breast adenocarcinoma and normal mammary epithelial cells. One single- (5a) and two novel double-modified analogs (5b, 13b) were more potent towards the MDA-MB-231 cell line than SAL or its C20-oxo analog 2. When select analogs were tested against the NCI-60 human tumor cell line panel, 4a showed particular sensitivity to ovarian cancer cell line SK-OV-3. Additionally, both SAL and 2 were potent ex vivo against human ER/PR+, Her2- invasive mammary carcinoma, with 2 showing minimal toxicity towards normal epithelial cells. The present findings highlight the therapeutic potential of SAL derivatives for select targeting of different cancer types. PMID: 31702860 [PubMed - ...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research

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Source: Expert Review of Clinical Pharmacology - Category: Drugs & Pharmacology Tags: Expert Rev Clin Pharmacol Source Type: research
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Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
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Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
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Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
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Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
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Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
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Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
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Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
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Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
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