TY  - JOUR
AU  - Radaković, Nataša
AU  - Nikolić, Andrea
AU  - Terzić-Jovanović, Nataša
AU  - Stojković, Pavle
AU  - Stanković, Nada
AU  - Šolaja, Bogdan
AU  - Opsenica, Igor
AU  - Pavić, Aleksandar
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5235
AB  - Candida albicans remains the main causal agent of candidiasis, the most common fungal infection with disturbingly high mortality rates worldwide. The limited diversity and efficacy of clinical antifungal drugs, exacerbated by emerging drug resistance, have resulted in the failure of current antifungal therapies. This imposes an urgent demand for the development of innovative strategies for effective eradication of candidal infections. While the existing clinical drugs display fungicidal or fungistatic activity, the strategy specifically targeting C. albicans filamentation, as the most important virulence trait, represents an attractive approach for overcoming the drawbacks related to clinical antifungals. The results acquired in this study revealed the significant potential of 5-aminotetrazoles as a new class of effective and safe anti-virulence agents. Moreover, these novel agents were active when applied both alone and in combination with clinically approved polyenes. Complete prevention of C. albicans morphogenetic yeast-to-hyphae transition was achieved at doses as low as 1.3 μM under conditions mimicking various filamentation-responsive stimuli in the human body, while no cardio- or hepatotoxicity was observed at doses as high as 200 μM. The treatment of C. albicans-infected zebrafish embryos with nystatin alone had low efficacy, while the combination of nystatin and selected 5-aminotetrazoles prevented fungal filamentation, successfully eliminating the infection and rescuing the infected embryos from lethal disseminated candidiasis. In addition, the most potent anti-virulence 5-aminotetrazole prevented C. albicans in developing the resistance to nystatin when applied in combination, keeping the fungus sensitive to the antifungal drug.
PB  - Elsevier
T2  - European Journal of Medicinal Chemistry
T1  - Unraveling the anti-virulence potential and antifungal efficacy of 5-aminotetrazoles using the zebrafish model of disseminated candidiasis
VL  - 230
SP  - 114137
DO  - 10.1016/j.ejmech.2022.114137
ER  - 

@article{
author = "Radaković, Nataša and Nikolić, Andrea and Terzić-Jovanović, Nataša and Stojković, Pavle and Stanković, Nada and Šolaja, Bogdan and Opsenica, Igor and Pavić, Aleksandar",
year = "2022",
abstract = "Candida albicans remains the main causal agent of candidiasis, the most common fungal infection with disturbingly high mortality rates worldwide. The limited diversity and efficacy of clinical antifungal drugs, exacerbated by emerging drug resistance, have resulted in the failure of current antifungal therapies. This imposes an urgent demand for the development of innovative strategies for effective eradication of candidal infections. While the existing clinical drugs display fungicidal or fungistatic activity, the strategy specifically targeting C. albicans filamentation, as the most important virulence trait, represents an attractive approach for overcoming the drawbacks related to clinical antifungals. The results acquired in this study revealed the significant potential of 5-aminotetrazoles as a new class of effective and safe anti-virulence agents. Moreover, these novel agents were active when applied both alone and in combination with clinically approved polyenes. Complete prevention of C. albicans morphogenetic yeast-to-hyphae transition was achieved at doses as low as 1.3 μM under conditions mimicking various filamentation-responsive stimuli in the human body, while no cardio- or hepatotoxicity was observed at doses as high as 200 μM. The treatment of C. albicans-infected zebrafish embryos with nystatin alone had low efficacy, while the combination of nystatin and selected 5-aminotetrazoles prevented fungal filamentation, successfully eliminating the infection and rescuing the infected embryos from lethal disseminated candidiasis. In addition, the most potent anti-virulence 5-aminotetrazole prevented C. albicans in developing the resistance to nystatin when applied in combination, keeping the fungus sensitive to the antifungal drug.",
publisher = "Elsevier",
journal = "European Journal of Medicinal Chemistry",
title = "Unraveling the anti-virulence potential and antifungal efficacy of 5-aminotetrazoles using the zebrafish model of disseminated candidiasis",
volume = "230",
pages = "114137",
doi = "10.1016/j.ejmech.2022.114137"
}

Radaković, N., Nikolić, A., Terzić-Jovanović, N., Stojković, P., Stanković, N., Šolaja, B., Opsenica, I.,& Pavić, A.. (2022). Unraveling the anti-virulence potential and antifungal efficacy of 5-aminotetrazoles using the zebrafish model of disseminated candidiasis. in European Journal of Medicinal Chemistry
Elsevier., 230, 114137.
https://doi.org/10.1016/j.ejmech.2022.114137

Radaković N, Nikolić A, Terzić-Jovanović N, Stojković P, Stanković N, Šolaja B, Opsenica I, Pavić A. Unraveling the anti-virulence potential and antifungal efficacy of 5-aminotetrazoles using the zebrafish model of disseminated candidiasis. in European Journal of Medicinal Chemistry. 2022;230:114137.
doi:10.1016/j.ejmech.2022.114137 .

Radaković, Nataša, Nikolić, Andrea, Terzić-Jovanović, Nataša, Stojković, Pavle, Stanković, Nada, Šolaja, Bogdan, Opsenica, Igor, Pavić, Aleksandar, "Unraveling the anti-virulence potential and antifungal efficacy of 5-aminotetrazoles using the zebrafish model of disseminated candidiasis" in European Journal of Medicinal Chemistry, 230 (2022):114137,
https://doi.org/10.1016/j.ejmech.2022.114137 . .

TY  - DATA
AU  - Nikolić, Andrea
AU  - Stanić, Jelena
AU  - Zlatar, Matija
AU  - Gruden, Maja
AU  - Anđelković, Boban
AU  - Selaković, Života
AU  - Ajdačić, Vladimir
AU  - Opsenica, Igor
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4444
AB  - Copies of 1H and 13C NMR spectra for the synthesized compounds; Extended computational results, and total electronic energies, number of imaginary frequencies;  Cartesian coordinates of all structures.
PB  - American Chemical Society (ACS)
T2  - The Journal of Organic Chemistry
T1  - Supporting information for: "Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines"
DO  - 10.1021/acs.joc.1c00282.s001
ER  - 

@misc{
author = "Nikolić, Andrea and Stanić, Jelena and Zlatar, Matija and Gruden, Maja and Anđelković, Boban and Selaković, Života and Ajdačić, Vladimir and Opsenica, Igor",
year = "2021",
abstract = "Copies of 1H and 13C NMR spectra for the synthesized compounds; Extended computational results, and total electronic energies, number of imaginary frequencies;  Cartesian coordinates of all structures.",
publisher = "American Chemical Society (ACS)",
journal = "The Journal of Organic Chemistry",
title = "Supporting information for: "Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines"",
doi = "10.1021/acs.joc.1c00282.s001"
}

Nikolić, A., Stanić, J., Zlatar, M., Gruden, M., Anđelković, B., Selaković, Ž., Ajdačić, V.,& Opsenica, I.. (2021). Supporting information for: "Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines". in The Journal of Organic Chemistry
American Chemical Society (ACS)..
https://doi.org/10.1021/acs.joc.1c00282.s001

Nikolić A, Stanić J, Zlatar M, Gruden M, Anđelković B, Selaković Ž, Ajdačić V, Opsenica I. Supporting information for: "Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines". in The Journal of Organic Chemistry. 2021;.
doi:10.1021/acs.joc.1c00282.s001 .

Nikolić, Andrea, Stanić, Jelena, Zlatar, Matija, Gruden, Maja, Anđelković, Boban, Selaković, Života, Ajdačić, Vladimir, Opsenica, Igor, "Supporting information for: "Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines"" in The Journal of Organic Chemistry (2021),
https://doi.org/10.1021/acs.joc.1c00282.s001 . .

TY  - JOUR
AU  - Nikolić, Andrea
AU  - Stanić, Jelena
AU  - Zlatar, Matija
AU  - Gruden, Maja
AU  - Anđelković, Boban
AU  - Selaković, Života
AU  - Ajdačić, Vladimir
AU  - Opsenica, Igor
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4443
AB  - The Pd-catalyzed N-arylation method for the synthesis of eighteen N,1-diaryl-1H-tetrazol-5-amine derivatives is reported. By running the reactions at 35 °C, compounds were isolated as single isomers since the undesired Dimroth rearrangement was completely suppressed. Furthermore, the Dimroth rearrangement of N,1-diaryl-1H-tetrazol-5-amines was rationalized by conducting comprehensive experiments and NMR analysis as well as density functional theory (DFT) calculations of thermodynamic stability of the compounds. It was established that the Dimroth rearrangement is thermodynamically controlled, and the equilibrium of the reaction is determined by the stability of the corresponding isomers. The mechanism was investigated by additional DFT calculations, and the opening of the tetrazole ring was shown to be the rate-determining step. By maneuvering Pd-catalyzed N-arylation and the subsequent Dimroth rearrangement, two more N,1-diaryl-1H-tetrazol-5-amine derivatives were acquired, which otherwise cannot be synthesized by employing the C–N cross-coupling reaction.
PB  - American Chemical Society (ACS)
T2  - The Journal of Organic Chemistry
T1  - Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines
VL  - 86
IS  - 6
SP  - 4794
EP  - 4803
DO  - 10.1021/acs.joc.1c00282
ER  - 

@article{
author = "Nikolić, Andrea and Stanić, Jelena and Zlatar, Matija and Gruden, Maja and Anđelković, Boban and Selaković, Života and Ajdačić, Vladimir and Opsenica, Igor",
year = "2021",
abstract = "The Pd-catalyzed N-arylation method for the synthesis of eighteen N,1-diaryl-1H-tetrazol-5-amine derivatives is reported. By running the reactions at 35 °C, compounds were isolated as single isomers since the undesired Dimroth rearrangement was completely suppressed. Furthermore, the Dimroth rearrangement of N,1-diaryl-1H-tetrazol-5-amines was rationalized by conducting comprehensive experiments and NMR analysis as well as density functional theory (DFT) calculations of thermodynamic stability of the compounds. It was established that the Dimroth rearrangement is thermodynamically controlled, and the equilibrium of the reaction is determined by the stability of the corresponding isomers. The mechanism was investigated by additional DFT calculations, and the opening of the tetrazole ring was shown to be the rate-determining step. By maneuvering Pd-catalyzed N-arylation and the subsequent Dimroth rearrangement, two more N,1-diaryl-1H-tetrazol-5-amine derivatives were acquired, which otherwise cannot be synthesized by employing the C–N cross-coupling reaction.",
publisher = "American Chemical Society (ACS)",
journal = "The Journal of Organic Chemistry",
title = "Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines",
volume = "86",
number = "6",
pages = "4794-4803",
doi = "10.1021/acs.joc.1c00282"
}

Nikolić, A., Stanić, J., Zlatar, M., Gruden, M., Anđelković, B., Selaković, Ž., Ajdačić, V.,& Opsenica, I.. (2021). Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines. in The Journal of Organic Chemistry
American Chemical Society (ACS)., 86(6), 4794-4803.
https://doi.org/10.1021/acs.joc.1c00282

Nikolić A, Stanić J, Zlatar M, Gruden M, Anđelković B, Selaković Ž, Ajdačić V, Opsenica I. Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines. in The Journal of Organic Chemistry. 2021;86(6):4794-4803.
doi:10.1021/acs.joc.1c00282 .

Nikolić, Andrea, Stanić, Jelena, Zlatar, Matija, Gruden, Maja, Anđelković, Boban, Selaković, Života, Ajdačić, Vladimir, Opsenica, Igor, "Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines" in The Journal of Organic Chemistry, 86, no. 6 (2021):4794-4803,
https://doi.org/10.1021/acs.joc.1c00282 . .

TY  - JOUR
AU  - Nikolić, Andrea
AU  - Stanić, Jelena
AU  - Zlatar, Matija
AU  - Gruden, Maja
AU  - Anđelković, Boban
AU  - Selaković, Života
AU  - Ajdačić, Vladimir
AU  - Opsenica, Igor
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4431
AB  - The Pd-catalyzed N-arylation method for the synthesis of eighteen N,1-diaryl-1H-tetrazol-5-amine derivatives is reported. By running the reactions at 35 °C, compounds were isolated as single isomers since the undesired Dimroth rearrangement was completely suppressed. Furthermore, the Dimroth rearrangement of N,1-diaryl-1H-tetrazol-5-amines was rationalized by conducting comprehensive experiments and NMR analysis as well as density functional theory (DFT) calculations of thermodynamic stability of the compounds. It was established that the Dimroth rearrangement is thermodynamically controlled, and the equilibrium of the reaction is determined by the stability of the corresponding isomers. The mechanism was investigated by additional DFT calculations, and the opening of the tetrazole ring was shown to be the rate-determining step. By maneuvering Pd-catalyzed N-arylation and the subsequent Dimroth rearrangement, two more N,1-diaryl-1H-tetrazol-5-amine derivatives were acquired, which otherwise cannot be synthesized by employing the C–N cross-coupling reaction.
PB  - American Chemical Society (ACS)
T2  - The Journal of Organic Chemistry
T1  - Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines
VL  - 86
IS  - 6
SP  - 4794
EP  - 4803
DO  - 10.1021/acs.joc.1c00282
ER  - 

@article{
author = "Nikolić, Andrea and Stanić, Jelena and Zlatar, Matija and Gruden, Maja and Anđelković, Boban and Selaković, Života and Ajdačić, Vladimir and Opsenica, Igor",
year = "2021",
abstract = "The Pd-catalyzed N-arylation method for the synthesis of eighteen N,1-diaryl-1H-tetrazol-5-amine derivatives is reported. By running the reactions at 35 °C, compounds were isolated as single isomers since the undesired Dimroth rearrangement was completely suppressed. Furthermore, the Dimroth rearrangement of N,1-diaryl-1H-tetrazol-5-amines was rationalized by conducting comprehensive experiments and NMR analysis as well as density functional theory (DFT) calculations of thermodynamic stability of the compounds. It was established that the Dimroth rearrangement is thermodynamically controlled, and the equilibrium of the reaction is determined by the stability of the corresponding isomers. The mechanism was investigated by additional DFT calculations, and the opening of the tetrazole ring was shown to be the rate-determining step. By maneuvering Pd-catalyzed N-arylation and the subsequent Dimroth rearrangement, two more N,1-diaryl-1H-tetrazol-5-amine derivatives were acquired, which otherwise cannot be synthesized by employing the C–N cross-coupling reaction.",
publisher = "American Chemical Society (ACS)",
journal = "The Journal of Organic Chemistry",
title = "Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines",
volume = "86",
number = "6",
pages = "4794-4803",
doi = "10.1021/acs.joc.1c00282"
}

Nikolić, A., Stanić, J., Zlatar, M., Gruden, M., Anđelković, B., Selaković, Ž., Ajdačić, V.,& Opsenica, I.. (2021). Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines. in The Journal of Organic Chemistry
American Chemical Society (ACS)., 86(6), 4794-4803.
https://doi.org/10.1021/acs.joc.1c00282

Nikolić A, Stanić J, Zlatar M, Gruden M, Anđelković B, Selaković Ž, Ajdačić V, Opsenica I. Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines. in The Journal of Organic Chemistry. 2021;86(6):4794-4803.
doi:10.1021/acs.joc.1c00282 .

Nikolić, Andrea, Stanić, Jelena, Zlatar, Matija, Gruden, Maja, Anđelković, Boban, Selaković, Života, Ajdačić, Vladimir, Opsenica, Igor, "Controlling Pd-Catalyzed N-Arylation and Dimroth Rearrangement in the Synthesis of N,1-Diaryl-1H-tetrazol-5-amines" in The Journal of Organic Chemistry, 86, no. 6 (2021):4794-4803,
https://doi.org/10.1021/acs.joc.1c00282 . .