Synthetic Transition from Thiourea-Based Compounds to Tetrazole Derivatives: Structure and Biological Evaluation of Synthesized New N-(Furan-2-ylmethyl)-1 H-tetrazol-5-amine Derivatives

从硫脲基化合物到四唑衍生物的合成转变:合成的新型 N-(呋喃-2-基甲基)-1 H-四唑-5-胺衍生物的结构和生物学评价

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作者:Daniel Szulczyk, Anna Bielenica, Piotr Roszkowski, Michał A Dobrowolski, Wioletta Olejarz, Sebastian Kmiecik, Małgorzata Podsiad, Marta Struga

Abstract

Twelve novel derivatives of N-(furan-2-ylmethyl)-1H-tetrazol-5-amine were synthesized. For obtained compound 8, its corresponding substrate single crystals were isolated and X-ray diffraction experiments were completed. In the initial stage of research, in silico structure-based pharmacological prediction was conducted. All compounds were screened for their antibacterial and antimycobacterial activities using standard and clinical strains. The cytotoxic activity was evaluated against a panel of human cancer cell lines, in contrast to normal (HaCaT) cell lines, by using the MTT method. All examined derivatives were found to be noncytotoxic against normal cell lines. Within the studied group, compound 6 showed the most promising results in antimicrobial studies. It inhibited four hospital S. epidermidis rods' growth, when applied at the amount of 4 µg/mL. However, the most susceptible to the presence of compound 6 was S. epidermidis T 5501 851/19 clinical strain, for which the MIC value was only 2 µg/mL. Finally, a pharmacophore model was established based on lead compounds from this and our previous work.

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