TY  - JOUR
AU  - Zveaghintseva, Marina
AU  - Stingaci, Eugenia
AU  - Pogrebnoi, Sergei
AU  - Smetanscaia, Anastasia
AU  - Valica, Vladimir
AU  - Uncu, Livia
AU  - Kravtsov, Victor
AU  - Melnik, Elena
AU  - Petrou, Anthi
AU  - Glamočlija, Jasmina
AU  - Soković, Marina
AU  - Carazo, Alejandro
AU  - Mladěnka, Přemysl
AU  - Poroikov, Vladimir
AU  - Geronikaki, Athina
AU  - Macaev, Fliur
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4305
AB  - Herein we report the synthesis of some new 1H-1,2,4-triazole functionalized chromenols
(3a–3n) via tandem reactions of 1-(alkyl/aryl)-2-(1H-1,2,4-triazole-1-yl) with salicylic aldehydes and
the evaluation of their antifungal activity. In silico prediction of biological activity spectra with
computer program PASS indicate that the compounds have a high novelty compared to the known
antifungal agents. We did not find any close analog among the over 580,000 pharmaceutical agents
in the Cortellis Drug Discovery Intelligence database at the similarity cutoff of 70%. The evaluation
of antifungal activity in vitro revealed that the highest activity was exhibited by compound 3k,
followed by 3n. Their MIC values for different fungi were 22.1–184.2 and 71.3–199.8  M, respectively.
Twelve from fourteen tested compounds were more active than the reference drugs ketoconazole and
bifonazole. The most sensitive fungus appeared to be Trichoderma viride, while Aspergillus fumigatus
was the most resistant one. It was found that the presence of the 2-(tert-butyl)-2H-chromen-2-ol
substituent on the 4th position of the triazole ring is very beneficial for antifungal activity. Molecular
docking studies on C. albicans sterol 14 -demethylase (CYP51) and DNA topoisomerase IV were used
to predict the mechanism of antifungal activities. According to the docking results, the inhibition
of CYP51 is a putative mechanism of antifungal activity of the novel chromenol derivatives. We
also showed that most active compounds have a low cytotoxicity, which allows us to consider them
promising antifungal agents for the subsequent testing activity in in vivo assays.
PB  - Basel: MDPI
T2  - Molecules
T1  - Chromenol Derivatives as Novel Antifungal Agents: Synthesis, In Silico and In Vitro Evaluation
IS  - 14
VL  - 26
DO  - 10.3390/molecules26144304
SP  - 4304
ER  - 

@article{
author = "Zveaghintseva, Marina and Stingaci, Eugenia and Pogrebnoi, Sergei and Smetanscaia, Anastasia and Valica, Vladimir and Uncu, Livia and Kravtsov, Victor and Melnik, Elena and Petrou, Anthi and Glamočlija, Jasmina and Soković, Marina and Carazo, Alejandro and Mladěnka, Přemysl and Poroikov, Vladimir and Geronikaki, Athina and Macaev, Fliur",
year = "2021",
abstract = "Herein we report the synthesis of some new 1H-1,2,4-triazole functionalized chromenols
(3a–3n) via tandem reactions of 1-(alkyl/aryl)-2-(1H-1,2,4-triazole-1-yl) with salicylic aldehydes and
the evaluation of their antifungal activity. In silico prediction of biological activity spectra with
computer program PASS indicate that the compounds have a high novelty compared to the known
antifungal agents. We did not find any close analog among the over 580,000 pharmaceutical agents
in the Cortellis Drug Discovery Intelligence database at the similarity cutoff of 70%. The evaluation
of antifungal activity in vitro revealed that the highest activity was exhibited by compound 3k,
followed by 3n. Their MIC values for different fungi were 22.1–184.2 and 71.3–199.8  M, respectively.
Twelve from fourteen tested compounds were more active than the reference drugs ketoconazole and
bifonazole. The most sensitive fungus appeared to be Trichoderma viride, while Aspergillus fumigatus
was the most resistant one. It was found that the presence of the 2-(tert-butyl)-2H-chromen-2-ol
substituent on the 4th position of the triazole ring is very beneficial for antifungal activity. Molecular
docking studies on C. albicans sterol 14 -demethylase (CYP51) and DNA topoisomerase IV were used
to predict the mechanism of antifungal activities. According to the docking results, the inhibition
of CYP51 is a putative mechanism of antifungal activity of the novel chromenol derivatives. We
also showed that most active compounds have a low cytotoxicity, which allows us to consider them
promising antifungal agents for the subsequent testing activity in in vivo assays.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Chromenol Derivatives as Novel Antifungal Agents: Synthesis, In Silico and In Vitro Evaluation",
number = "14",
volume = "26",
doi = "10.3390/molecules26144304",
pages = "4304"
}

Zveaghintseva, M., Stingaci, E., Pogrebnoi, S., Smetanscaia, A., Valica, V., Uncu, L., Kravtsov, V., Melnik, E., Petrou, A., Glamočlija, J., Soković, M., Carazo, A., Mladěnka, P., Poroikov, V., Geronikaki, A.,& Macaev, F.. (2021). Chromenol Derivatives as Novel Antifungal Agents: Synthesis, In Silico and In Vitro Evaluation. in Molecules
Basel: MDPI., 26(14), 4304.
https://doi.org/10.3390/molecules26144304

Zveaghintseva M, Stingaci E, Pogrebnoi S, Smetanscaia A, Valica V, Uncu L, Kravtsov V, Melnik E, Petrou A, Glamočlija J, Soković M, Carazo A, Mladěnka P, Poroikov V, Geronikaki A, Macaev F. Chromenol Derivatives as Novel Antifungal Agents: Synthesis, In Silico and In Vitro Evaluation. in Molecules. 2021;26(14):4304.
doi:10.3390/molecules26144304 .

Zveaghintseva, Marina, Stingaci, Eugenia, Pogrebnoi, Sergei, Smetanscaia, Anastasia, Valica, Vladimir, Uncu, Livia, Kravtsov, Victor, Melnik, Elena, Petrou, Anthi, Glamočlija, Jasmina, Soković, Marina, Carazo, Alejandro, Mladěnka, Přemysl, Poroikov, Vladimir, Geronikaki, Athina, Macaev, Fliur, "Chromenol Derivatives as Novel Antifungal Agents: Synthesis, In Silico and In Vitro Evaluation" in Molecules, 26, no. 14 (2021):4304,
https://doi.org/10.3390/molecules26144304 . .