000097436 001__ 97436 000097436 005__ 20210902121842.0 000097436 0247_ $$2doi$$a10.3390/ph13120482 000097436 0248_ $$2sideral$$a121734 000097436 037__ $$aART-2020-121734 000097436 041__ $$aeng 000097436 100__ $$aValls, A. 000097436 245__ $$aImidazole and imidazolium antibacterial drugs derived from amino acids 000097436 260__ $$c2020 000097436 5060_ $$aAccess copy available to the general public$$fUnrestricted 000097436 5203_ $$aThe antibacterial activity of imidazole and imidazolium salts is highly dependent upon their lipophilicity, which can be tuned through the introduction of different hydrophobic substituents on the nitrogen atoms of the imidazole or imidazolium ring of the molecule. Taking this into consideration, we have synthesized and characterized a series of imidazole and imidazolium salts derived from L-valine and L-phenylalanine containing different hydrophobic groups and tested their antibacterial activity against two model bacterial strains, Gram-negative E. coli and Gram-positive B. subtilis. Importantly, the results demonstrate that the minimum bactericidal concentration (MBC) of these derivatives can be tuned to fall close to the cytotoxicity values in eukaryotic cell lines. The MBC value of one of these compounds toward B. subtilis was found to be lower than the IC50 cytotoxicity value for the control cell line, HEK-293. Furthermore, the aggregation behavior of these compounds has been studied in pure water, in cell culture media, and in mixtures thereof, in order to determine if the compounds formed self-assembled aggregates at their bioactive concentrations with the aim of determining whether the monomeric species were in fact responsible for the observed antibacterial activity. Overall, these results indicate that imidazole and imidazolium compounds derived from L-valine and L-phenylalanine—with different alkyl lengths in the amide substitution—can serve as potent antibacterial agents with low cytotoxicity to human cell lines. 000097436 536__ $$9info:eu-repo/grantAgreement/EC/H2020/845427/EU/Peptide-functionalized POMs as biofilm disruption agents: searching for synergy in bactericidal materials/PePiPOM$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 845427-PePiPOM$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-109333RB-I00 000097436 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000097436 590__ $$a5.863$$b2020 000097436 591__ $$aPHARMACOLOGY & PHARMACY$$b38 / 275 = 0.138$$c2020$$dQ1$$eT1 000097436 591__ $$aCHEMISTRY, MEDICINAL$$b9 / 63 = 0.143$$c2020$$dQ1$$eT1 000097436 592__ $$a1.294$$b2020 000097436 593__ $$aDrug Discovery$$c2020$$dQ1 000097436 593__ $$aPharmaceutical Science$$c2020$$dQ1 000097436 593__ $$aMolecular Medicine$$c2020$$dQ1 000097436 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000097436 700__ $$aAndreu, J.J. 000097436 700__ $$aFalomir, E. 000097436 700__ $$aLuis, S.V. 000097436 700__ $$0(orcid)0000-0002-3830-7847$$aAtrián-Blasco, E. 000097436 700__ $$0(orcid)0000-0003-4848-414X$$aMitchell, S.G.$$uUniversidad de Zaragoza 000097436 700__ $$aAltava, B. 000097436 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica 000097436 773__ $$g13, 12 (2020), 482 [1-17]$$pPharmaceuticals$$tPharmaceuticals$$x1424-8247 000097436 8564_ $$s1487134$$uhttps://zaguan.unizar.es/record/97436/files/texto_completo.pdf$$yVersión publicada 000097436 8564_ $$s514590$$uhttps://zaguan.unizar.es/record/97436/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000097436 909CO $$ooai:zaguan.unizar.es:97436$$particulos$$pdriver 000097436 951__ $$a2021-09-02-10:24:26 000097436 980__ $$aARTICLE