Imidazoles and benzimidazoles are privileged heterocyclic bioactive compounds used with success in the clinical practice of innumerous diseases. Although there are many advancements in cancer therapy, microtubules remain as one of the few macromolecular targets validated for planning active anti-cancer compounds, and the design of drugs that modulate microtubule dynamics in unknown sites of tubulin is one of the goals of the medicinal chemistry. The discussion of the role of new and commercially available imidazole and benzimidazole derivatives as tubulin modulators is scattered throughout scientific literature, and indicates that these compounds have a tubulin modulation mechanism different from that of tubulin modulators clinically available, such as paclitaxel, docetaxel, vincristine and vinblastine. In fact, recent literature indicates that these derivatives inhibit microtubule formation binding to the colchicine site, present good pharmacokinetic properties and are capable of overcoming multidrug resistance in many cell lines. The understanding of the mechanisms involved in the imidazoles/benzimidazoles modulation of microtubule dynamics is very important to develop new strategies to overcome the resistance to anti-cancer drugs and to discover new biomarkers and targets for cancer chemotherapy.

The cancer stem cell (CSC) theory is current strategy of cancer treatment. Cancers follow pathways of cancer stem cell such as Notch, Wnt and Hedgehog can be addressed with natural products or synthetic drugs to diminish the chance of new tumours. The cancer growth can also be suppressed by aiming the tumourigenic stem cells alone, instead of targeting at reducing complete tumour dimension. The recurrence of tumours after years of disease-free survival has prompted interest in the concept that cancers may have a stem cell basis. Current assumption holds that < 5% of the tumour mass may be chemo-resistant and radio-resistant, harbouring stem-like properties that impel tumour survival, development, and metastasis. There is intense an investigation to interpret CSCs based on self-renewal and multi-lineage differentiation. Nevertheless, no successful targeted therapies have reached the clinic. The ionophore antibiotic salinomycin that selectively kills breast CSCs seems to be a promising anticancer drug. Clinical trials conducted by the NIH (National Institute of Health) on several synthetic drugs demonstrate the current importance of the issue and predict a bright future for such molecular weapons against cancer.

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