α‐ω alkenyl‐bis‐S‐guanidine thiourea‐dihydrobromide affects HeLa tumor cells growth hampering tubulin polymerization

Cancer is going to be the first cause of mortality worldwide in the 21th century. It is considered a multifactorial disease that results from the combined influence of many genetic aberrations, leading to abnormal cell proliferation. As microtubules are strongly implicated with cellular growth, they represent an important target for cancer treatment. The well-known Microtubule Targeting Agents (MTAs) including paclitaxel, colchicine and vinca alkaloids are commonly used in the treatment of various cancers. However, adverse effects and drug resistance are the major limitation in their clinical use. With the aim to find new candidates able to induce microtubule alteration with reduced toxic effects or drug resistance, we studied a new small series of derivatives that present imidazolinic, guanidinic, thioureidic and hydrazinic groups (1-9). All the compounds were tested for their antitumor activity against a panel of six tumoral cell models. Particularly, compound 8 (1,9-nonanediyl-bis-Samidinothiourea-dihydrobromide) showed the lower IC50 value against HeLa cells, together with a low cytotoxicity on the normal cells. This compound was able to induce the apoptotic mitochondrial pathway and inhibited the tubulin polymerization with a similar efficacy of Vinblastine and Nocodazole. Taken together, these promising biological properties make compound 8 useful for the development of novel therapeutic approaches in cancer treatment.