α–ω Alkenyl‐bis‐S‐Guanidine Thiourea Dihydrobromide Affects HeLa Cell Growth Hampering Tubulin Polymerization

Abstract

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 in 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 major limitations in their clinical use. To find new candidates able to induce microtubule alteration with reduced toxic effects or drug resistance, we studied a small new 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. In particular, compound 8 (nonane-1,9diyl-bis-S-amidinothiourea dihydrobromide) showed the lowest IC 50 value against HeLa cells, together with a low cytotoxicity for normal cells. This compound was able to induce the apoptotic mitochondrial pathway and inhibited tubulin polymerization with a similar efficacy to vinblastine and nocodazole. Taken together, these promising biological properties make compound 8 useful for the development of novel therapeutic approaches in cancer treatment.

Annona cherimola Mill. Leaf Extracts Affect Melanoma Cells Growth and Progression

“…Cells were grown in complete medium, and, before being treated, they were starved in serum-free medium for 24 h for the cell-cycle synchronization. Cells were then treated with increasing concentrations (from 0.001 to 100 μg/mL) of each extract dissolved in DMSO for 72 h. Cell viability was assessed using the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide reagent (MTT), according to the manufacturer’s protocol (Sigma–Aldrich, Milan, Italy), as previously described [ 26 ]. For each sample, mean absorbance, measured at 570 nm, was expressed as a percentage of the control and plotted versus drug concentration to determine the IC 50 values for each cell line, using GraphPad Prism 9 software (GraphPad Inc., San Diego, CA, USA).…”

Bis-Thiourea Quaternary Ammonium Salts as Potential Agents against Bacterial Strains from Food and Environmental Matrices

“…All strains were maintained as freeze-dried stocks in reconstituted (11% w/v) skim milk, containing 0.1% w/v ascorbic acid and routinely cultivated in optimal growth conditions [35] (Table 2). These bacteria were chosen to represent the diversity of species of food-borne (labels 1-22; 31-35) and environment-borne (labels [23][24][25][26][27][28][29][30]36) Gram-positive and Gram-negative bacteria.…”

“…In this paper, four bis-thiourea derivatives ( Table 1 ) have been studied for their antibacterial activity against Gram-positive and Gram-negative bacteria on different bacterial strains isolated from food and environmental matrices. Compounds 1 – 3 were chosen among our QASs previously studied, with alkyl chains of different lengths [ 30 , 31 , 32 ]. In addition, some guanidine derivatives had shown interesting antibacterial activity, with a mechanism of action based on the strong electrostatic interactions between their positive charges and the electronegative envelope of bacteria [ 33 , 34 ].…”

Diarylureas as Antitumor Agents

“…This review focuses on diarylureas, i.e., ureas substituted with two aromatic moieties also known as bis-aryl ureas. Diarylureas are found in numerous heterocyclic compounds with various biological activities [4], such as antithrombotic, antimalarial, antibacterial, antinflammatory, and anticancer [5,6]. In particular, diarylurea is a prominent pharmacophore in anticancer drugs.…”