Screening of Benzimidazole-Based Anthelmintics and Their Enantiomers as Repurposed Drug Candidates in Cancer Therapy.

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ID: 265446
2021
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Ranked #11 of 30 articles by views in Pharmaceuticals (Basel, Switzerland)

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Abstract
Repurposing of approved non-antitumor drugs represents a promising and affordable strategy that may help to increase the repertoire of effective anticancer drugs. Benzimidazole-based anthelmintics are antiparasitic drugs commonly employed both in human and veterinary medicine. Benzimidazole compounds are being considered for drug repurposing due to antitumor activities displayed by some members of the family. In this study, we explored the effects of a large series of benzimidazole-based anthelmintics (and some enantiomerically pure forms of those containing a stereogenic center) on the viability of different tumor cell lines derived from paraganglioma, pancreatic and colorectal cancer. Flubendazole, parbendazole, oxibendazole, mebendazole, albendazole and fenbendazole showed the most consistent antiproliferative effects, displaying IC values in the low micromolar range, or even in the nanomolar range. In silico evaluation of their physicochemical, pharmacokinetics and medicinal chemistry properties also provided useful information related to the chemical structures and potential of these compounds. Furthermore, in view of the potential repurposing of these drugs in cancer therapy and considering that pharmaceutically active compounds may have different mechanisms of action, we performed an in silico target prediction to assess the polypharmacology of these benzimidazoles, which highlighted previously unknown cancer-relevant molecular targets.
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florio2021screeningpharmaceuticals Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Florio, Rosalba;Carradori, Simone;Veschi, Serena;Brocco, Davide;Di Genni, Teresa;Cirilli, Roberto;Casulli, Adriano;Cama, Alessandro;De Lellis, Laura;
Journal Pharmaceuticals (Basel, Switzerland)
Year 2021
DOI
372
URL
Keywords
Benzimidazoles Pancreatic cancer colorectal cancer paraganglioma drug repositioning target prediction enantioselective hplc pharmacokinetic parameters

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