Perspectives of Benzimidazole Derivatives as Anticancer Agents in the New Era

Abstract

Cancer is one of the deadliest diseases nowadays and is a great topic for research as the challenging task is to develop new entities with selectivity towards cancerous cells. Heterocyclic compounds are of great importance in medicinal chemistry as they possess an extensive range of therapeutic applications. Benzimidazole is one such important heterocyclic organic compound having structural analogy to nucleotides found in human body and hence is an important pharmacophore in medicinal chemistry. A variety of marketed drugs containing benzimidazole are thiabendazole, flubendazole (anthelmintic), astmizole (antihistaminic), lansoprazole and omeprazole (antiulcerative). In the light of the above facts, this review is an attempt to summarize the collective contributions from the authors around the world in the field of anticancer agents. This review highlights synthetic schemes and anticancer activity results of the research done in the past years.

The metabolism of flubendazole in human liver and cancer cell lines

“…1,2 Widely used in veterinary medicine for a long time, Flubendazole (FLU) is a benzimidazole anthelmintic drug with low mammalian toxicity and high effectivity against a wide range of helminth species. Several drugs originally approved for indications other than cancer treatment have recently been found to exhibit a cytostatic effect on cancer cells.…”

“…1,2 Widely used in veterinary medicine for a long time, Flubendazole (FLU) is a benzimidazole anthelmintic drug with low mammalian toxicity and high effectivity against a wide range of helminth species. 1,2 Several promising reports describing the antiproliferative effects of benzimidazoles, including FLU, in cancer cell lines and their anti-tumor properties in animal models have been published. 4 The molecular mechanism of action of benzimidazoles is based on specific binding to tubulin, the microtubule subunit protein.…”

“…These drugs could be expediently repurposed as anticancer agents, since they have already been tested for toxicity in humans and animals. 1,2 Widely used in veterinary medicine for a long time, Flubendazole (FLU) is a benzimidazole anthelmintic drug with low mammalian toxicity and high effectivity against a wide range of helminth species. 3 Recently, however, FLU has been registered in Europe for treatment of gut-residing nematodes in humans.…”

“…5 The microtubule-disrupting properties of benzimidazoles has raised interest in these compounds as possible anti-cancer agents, as microtubules play key roles in the proliferation, trafficking and migration of eukaryotic cells, including the invasion and metastatic spread of tumor cells. 1,2 Several promising reports describing the antiproliferative effects of benzimidazoles, including FLU, in cancer Abbreviations: CBR1, carbonyl reductase 1; COMT, catechol O-methyl transferase; FLU, flubendazole; FLUR, flubendazole with a reduced carbonyl group cell lines and their anti-tumor properties in animal models have been published. In leukemia and myeloma cell lines, FLU has been found to induce cell death very effectively.…”

Radiosynthesis of microtubule‐targeted theranostic methyl N‐[5‐(3’‐radiohalobenzoyl)‐1H‐benzimidazol‐2‐yl]carbamates

“…Drugs that target the cytoskeleton and spindle apparatus of tumor cells belong to one of the most important classes of chemotherapeutics. [1][2][3][4][5] Functional microtubules are essential for proliferation, invasion and migration of cancer cells. Microtubule-binding drugs such as taxanes, vinca alkaloids and epothilones are widely used as the standard first-line option treatment in many cancers 2,6,7 but their utility is frequently limited by significant toxicities and primary or acquired resistance.…”