Emerging Perspectives on the Antiparasitic Mebendazole as a Repurposed Drug for the Treatment of Brain Cancers

Abstract

Repurposing approved non-antitumor drugs is a promising and affordable strategy in drug discovery to identify new therapeutic uses different from the original medical indication that may help increase the number of possible, effective anticancer drugs. The use of drugs in ways other than their original FDA-approved indications could offer novel avenues such as bypassing the chemoresistance and recurrence seen with conventional therapy and treatment; moreover, it can offer a safe and economic strategy for combination therapy. Recent works have demonstrated the anticancer properties of the FDA-approved drug Mebendazole. This synthetic benzimidazole proved effective against a broad spectrum of intestinal Helminthiasis. Mebendazole can penetrate the blood–brain barrier and has been shown to inhibit the malignant progression of glioma by targeting signaling pathways related to cell proliferation, apoptosis, or invasion/migration, or by increasing the sensitivity of glioma cells to conventional chemotherapy or radiotherapy. Moreover, several preclinical models and ongoing clinical trials explore the efficacy of Mebendazole in multiple cancers, including acute myeloid leukemia, brain cancer, oropharyngeal squamous cell carcinoma, breast cancer, gastrointestinal cancer, lung carcinoma, adrenocortical carcinoma, prostate cancer, and head and neck cancer. The present review summarizes central literature regarding the anticancer effects of MBZ in cancer cell lines, animal tumor models, and clinical trials to suggest possible strategies for safe and economical combinations of anticancer therapies in brain cancer. Mebendazole might be an excellent candidate for the treatment of brain tumors because of its efficacy both when used as monotherapy and in combination as an enhancement to standard chemotherapeutics and radiotherapy, due to its effectiveness on tumor angiogenesis inhibition, cell cycle arrest, apoptosis induction, and targeting of critical pathways involved in cancer such as Hedgehog signaling. Therefore, attention to MBZ repurposing has recently increased because of its potential therapeutic versatility and significant clinical implications, such as reducing medical care costs and optimizing existing therapies. Using new treatments is essential, particularly when current therapeutics for patients with brain cancer fail.

Medical management of cystic echinococcosis

“…The ability of mebendazole to inhibit microtubule formation and glucose uptake, plus its ability to pass through the blood-brain barrier has made it a compound of interest for the possible treatment of brain cancers. Phase I trials have been undertaken and it is now in phase II and III trials [5]. Development of new presentations, for example, using nanocarrier-based formulations, pro-drug formulations, and solid dispersions, to improve bioavailability and possibly reduce inter-individual variability in in-vivo drug levels, is an active area of oncology research.…”

Recent Advances in the Anticancer Applications of Benzimidazole Derivatives

“…In this trend, benzimidazoles are considered one of the most privileged scaffolds with varying biological properties, constituting the effective ingredient in numerous valuable drugs [27] . The benzimidazole motif satisfies the minimum constructional requisites essential in pharmaceutical chemistry [28–30] . Indeed, the benzimidazole skeleton possesses applicable similarity to natural nucleotides, which provides the possibility and facility of using it to interact with the active sites of the biopolymers in living organisms.…”

“…[27] The benzimidazole motif satisfies the minimum constructional requisites essential in pharmaceutical chemistry. [28][29][30] Indeed, the benzimidazole skeleton possesses applicable similarity to natural nucleotides, which provides the possibility and facility of using it to interact with the active sites of the biopolymers in living organisms. As a noticeable instance, the structural correspondence of 2-aminobenzimidazole with purine delineated a novel path in using such building blocks for various biological purposes.…”

Synthesis, Cytotoxic Activity, Docking and MD Simulation of N,N‐Disubstituted New Benzimidazolium Salts

“…In this regard, benzimidazoles are contemplated as one of the most privileged building blocks with diverse pharmacological characteristics, comprising the potent ingredient in multifarious valuable drugs [6] . The benzimidazole motif satisfies the minimum constructional requisites that play a highly crucial function in pharmaceutical chemistry [7–9] . Indeed, the benzimidazole skeleton possesses applicable similarity to natural nucleotides, which provides the possibility and facility of using it to interact with the active sites of the biopolymers in living organisms.…”

“…[6] The benzimidazole motif satisfies the minimum constructional requisites that play a highly crucial function in pharmaceutical chemistry. [7][8][9] Indeed, the benzimidazole skeleton possesses applicable similarity to natural nucleotides, which provides the possibility and facility of using it to interact with the active sites of the biopolymers in living organisms. As a noticeable instance, the structural correspondence of 2-aminobenzimidazole with purine delineated a novel path on the progress of using such frameworks for assorted biological purposes.…”