Isothioureas are a class of amphiphilic compounds carrying a highly basic isothiourea
group of pKa ranging between 10 and 11. Hence, they exist in protonated (cation) form at physiological
pH, a characteristic is of key importance for their pharmacological activity. Recently, we have
found that a number of S-pentabromobenzylisothiourea derivatives show substantial cytotoxicity toward
a variety of human glioblastoma, leukemia, and adenocarcinoma cell lines. Whereas there is a
growing body of data on aliphatic and alkylaromatic isothioureas, little attention was given to this day
to heterocyclic isotiourea derivatives. Here we report on the synthesis and pharmacological in vitro properties of 10 novel
S-(benzimidazol-2-ylmethyl)- and S-(5,6-dichlorobenzimidazol-2-ylmethyl)isothiourea derivatives. The compounds were
obtained by the condensation of the respective 2-chloromethyl benzimidazoles with various substituted N(N’)-thioureas.
Besides the essential physicochemical characteristics (H-NMR, UV, elemental analysis) of the new compounds, their
log P values, which are of key importance for in vivo drug distribution and interactions, were determined. Pharmacological
(anticancer) activity of the compounds was evaluated based on their ability to induce apoptosis in exponentially growing
cultures of the human acute myelogenous leukemia cell line KG-1; the apoptosis was assessed with a variety of flow
cytometric methods. Of the novel compounds tested, the most potent apoptosis inducer in KG-1 cells was N-methyl-S-
(5,6-dichloro-1H-benzimidazol-2-ylmethyl)isothiouronium chloride (ClBMMe).