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

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 14; no. 4; p. 372
• Main Authors: Florio, Rosalba, Carradori, Simone, Veschi, Serena, Brocco, Davide, Di Genni, Teresa, Cirilli, Roberto, Casulli, Adriano, Cama, Alessandro, De Lellis, Laura
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17-04-2021; MDPI
• Subjects: benzimidazoles; Bioavailability; Cancer therapies; Chemotherapy; Colorectal cancer; drug repositioning; Drugs; enantioselective HPLC; Pancreatic cancer; paraganglioma; Tumors; pancreatic cancer; target prediction; colorectal cancer; pharmacokinetic parameters; enantioselective HPLC; benzimidazoles; drug repositioning; paraganglioma
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph14040372

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.