Correlation of structural features of novel 1,2,3-triazoles with their neurotoxic and tumoricidal properties.

Correlation of structural features of novel 1,2,3-triazoles with their neurotoxic and tumoricidal properties. Chem Biol Interact. 2018 Jun 23;: Authors: de Souza-Fagundes EM, Delp J, Prazeres PDM, Marques LB, Carmo AML, Stroppa PHF, Glanzmann N, Kisitu J, Szamosvàri D, Böttcher T, Leist M, da Silva AD Abstract Triazoles are interesting templates for novel chemotherapeutic drugs. We synthesized here 17 1,3,4-substituted-1,2,3-triazoles that differed in their 1'-substituent (variable alkyl chain lengths C3-C12), the 3'-substituent (no substituent, -methyl or -propyl) or the salt form obtained. Several of the compounds were cytotoxic (μM range) for tumor cells (HL-60, JURKAT, MCF-7, HCT-116), and when the effect was compared to non-transformed cells (Vero), selectivity ratios of up to 23-fold were obtained. To estimate the liability of these potential drug candidates for triggering neurotoxicity, we used the LUHMES cell-based NeuriTox assay. This test quantifies damage to the neurites of human neurons. The four most potent tumoricidal compounds were found to be neurotoxic in a concentration range similar to the one showing tumor cell toxicity. As the neurites of the LUHMES neurons were affected at >4-fold lower concentrations than the overall cell viability, the novel triazoles were classified as specific neurotoxicants. The structure-activity relationship (SAR) for neurotoxicity was sharply defined and correlated with the one for...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research