TY  - JOUR
AU  - Dimic, Dusan S.
AU  - Kaluderović, Goran N.
AU  - Avdović, Edina H.
AU  - Milenković, Dejan
AU  - Živanović, Marko N.
AU  - Potocnak, Ivan
AU  - Samolova, Erika
AU  - Dimitrijević, Milena
AU  - Saso, Luciano
AU  - Marković, Zoran S.
AU  - Dimitrić-Marković, Jasmina
PY  - 2022
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1534
AB  - In this contribution, four new compounds synthesized from 4-hydroxycoumarin and tyramine/octopamine/norepinephrine/3-methoxytyramine are characterized spectroscopically (IR and NMR), chromatographically (UHPLC-DAD), and structurally at the B3LYP/6-311++G*(d,p) level of theory. The crystal structure of the 4-hydroxycoumarin-octopamine derivative was solved and used as a starting geometry for structural optimization. Along with the previously obtained 4-hydroxycoumarin-dopamine derivative, the intramolecular interactions governing the stability of these compounds were quantified by NBO and QTAIM analyses. Condensed Fukui functions and the HOMO-LUMO gap were calculated and correlated with the number and position of OH groups in the structures. In vitro cytotoxicity experiments were performed to elucidate the possible antitumor activity of the tested substances. For this purpose, four cell lines were selected, namely human colon cancer (HCT-116), human adenocarcinoma (HeLa), human breast cancer (MDA-MB-231), and healthy human lung fibroblast (MRC-5) lines. A significant selectivity towards colorectal carcinoma cells was observed. Molecular docking and molecular dynamics studies with carbonic anhydrase, a prognostic factor in several cancers, complemented the experimental results. The calculated MD binding energies coincided well with the experimental activity, and indicated 4-hydroxycoumarin-dopamine and 4-hydroxycoumarin-3-methoxytyramine as the most active compounds. The ecotoxicology assessment proved that the obtained compounds have a low impact on the daphnia, fish, and green algae population.
PB  - MDPI, Basel
T2  - International Journal of Molecular Sciences
T1  - Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives
IS  - 2
VL  - 23
DO  - 10.3390/ijms23021001
ER  - 

@article{
author = "Dimic, Dusan S. and Kaluderović, Goran N. and Avdović, Edina H. and Milenković, Dejan and Živanović, Marko N. and Potocnak, Ivan and Samolova, Erika and Dimitrijević, Milena and Saso, Luciano and Marković, Zoran S. and Dimitrić-Marković, Jasmina",
year = "2022",
abstract = "In this contribution, four new compounds synthesized from 4-hydroxycoumarin and tyramine/octopamine/norepinephrine/3-methoxytyramine are characterized spectroscopically (IR and NMR), chromatographically (UHPLC-DAD), and structurally at the B3LYP/6-311++G*(d,p) level of theory. The crystal structure of the 4-hydroxycoumarin-octopamine derivative was solved and used as a starting geometry for structural optimization. Along with the previously obtained 4-hydroxycoumarin-dopamine derivative, the intramolecular interactions governing the stability of these compounds were quantified by NBO and QTAIM analyses. Condensed Fukui functions and the HOMO-LUMO gap were calculated and correlated with the number and position of OH groups in the structures. In vitro cytotoxicity experiments were performed to elucidate the possible antitumor activity of the tested substances. For this purpose, four cell lines were selected, namely human colon cancer (HCT-116), human adenocarcinoma (HeLa), human breast cancer (MDA-MB-231), and healthy human lung fibroblast (MRC-5) lines. A significant selectivity towards colorectal carcinoma cells was observed. Molecular docking and molecular dynamics studies with carbonic anhydrase, a prognostic factor in several cancers, complemented the experimental results. The calculated MD binding energies coincided well with the experimental activity, and indicated 4-hydroxycoumarin-dopamine and 4-hydroxycoumarin-3-methoxytyramine as the most active compounds. The ecotoxicology assessment proved that the obtained compounds have a low impact on the daphnia, fish, and green algae population.",
publisher = "MDPI, Basel",
journal = "International Journal of Molecular Sciences",
title = "Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives",
number = "2",
volume = "23",
doi = "10.3390/ijms23021001"
}

Dimic, D. S., Kaluderović, G. N., Avdović, E. H., Milenković, D., Živanović, M. N., Potocnak, I., Samolova, E., Dimitrijević, M., Saso, L., Marković, Z. S.,& Dimitrić-Marković, J.. (2022). Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives. in International Journal of Molecular Sciences
MDPI, Basel., 23(2).
https://doi.org/10.3390/ijms23021001

Dimic DS, Kaluderović GN, Avdović EH, Milenković D, Živanović MN, Potocnak I, Samolova E, Dimitrijević M, Saso L, Marković ZS, Dimitrić-Marković J. Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives. in International Journal of Molecular Sciences. 2022;23(2).
doi:10.3390/ijms23021001 .

Dimic, Dusan S., Kaluderović, Goran N., Avdović, Edina H., Milenković, Dejan, Živanović, Marko N., Potocnak, Ivan, Samolova, Erika, Dimitrijević, Milena, Saso, Luciano, Marković, Zoran S., Dimitrić-Marković, Jasmina, "Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives" in International Journal of Molecular Sciences, 23, no. 2 (2022),
https://doi.org/10.3390/ijms23021001 . .

TY  - JOUR
AU  - Draca, Dijana
AU  - Mijatović, Sanja
AU  - Krajnović, Tamara
AU  - Bogdanović Pristov, Jelena
AU  - Dukic, Tatjana
AU  - Kaluderović, Goran N.
AU  - Wessjohann, Ludger A.
AU  - Maksimović-Ivanić, Danijela
PY  - 2019
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/1228
AB  - Synthetic tubugis are equally potent but more stable than their natural forms. Their anticancer potential was estimated on a solid melanoma in vitro and in vivo. Tubugi-1 induced the apoptosis in B16 cells accompanied with strong intracellular production of reactive species, subsequently imposing glutathione and thiol group depletion. Paradoxically, membrane lipids were excluded from the cascade of intracellular oxidation, according to malondialdehyde decrease. Although morphologically apoptosis was typical, externalization of phosphatidylserine (PS) as an early apoptotic event was not detected. Even their exposition is pivotal for apoptotic cell eradication, primary macrophages successfully eliminated PS-deficient tubugi-1 induced apoptotic cells. The tumor volume in animals exposed to the drug in therapeutic mode was reduced in comparison to control as well as to paclitaxeltreated animals Importantly, macrophages isolated from tubugi-1 treated animals possessed conserved phagocytic activity and were functionally and phenotypically recognized as Ml. The cytotoxic effect of tubugi-1 is accomplished through its ability to polarize the macrophages toward Ml, probably by PS independent apoptotic cell engulfment. The unique potential of tubugi-1 to prime the innate immune response through the induction of a specific pattern of tumor cell apoptosis can be of extraordinary importance from fundamental and applicable aspects.
PB  - Elsevier Inc, San Diego
T2  - Experimental Cell Research
T1  - The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model
EP  - 170
IS  - 2
SP  - 159
VL  - 380
DO  - 10.1016/j.yexcr.2019.04.028
ER  - 

@article{
author = "Draca, Dijana and Mijatović, Sanja and Krajnović, Tamara and Bogdanović Pristov, Jelena and Dukic, Tatjana and Kaluderović, Goran N. and Wessjohann, Ludger A. and Maksimović-Ivanić, Danijela",
year = "2019",
abstract = "Synthetic tubugis are equally potent but more stable than their natural forms. Their anticancer potential was estimated on a solid melanoma in vitro and in vivo. Tubugi-1 induced the apoptosis in B16 cells accompanied with strong intracellular production of reactive species, subsequently imposing glutathione and thiol group depletion. Paradoxically, membrane lipids were excluded from the cascade of intracellular oxidation, according to malondialdehyde decrease. Although morphologically apoptosis was typical, externalization of phosphatidylserine (PS) as an early apoptotic event was not detected. Even their exposition is pivotal for apoptotic cell eradication, primary macrophages successfully eliminated PS-deficient tubugi-1 induced apoptotic cells. The tumor volume in animals exposed to the drug in therapeutic mode was reduced in comparison to control as well as to paclitaxeltreated animals Importantly, macrophages isolated from tubugi-1 treated animals possessed conserved phagocytic activity and were functionally and phenotypically recognized as Ml. The cytotoxic effect of tubugi-1 is accomplished through its ability to polarize the macrophages toward Ml, probably by PS independent apoptotic cell engulfment. The unique potential of tubugi-1 to prime the innate immune response through the induction of a specific pattern of tumor cell apoptosis can be of extraordinary importance from fundamental and applicable aspects.",
publisher = "Elsevier Inc, San Diego",
journal = "Experimental Cell Research",
title = "The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model",
pages = "170-159",
number = "2",
volume = "380",
doi = "10.1016/j.yexcr.2019.04.028"
}

Draca, D., Mijatović, S., Krajnović, T., Bogdanović Pristov, J., Dukic, T., Kaluderović, G. N., Wessjohann, L. A.,& Maksimović-Ivanić, D.. (2019). The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model. in Experimental Cell Research
Elsevier Inc, San Diego., 380(2), 159-170.
https://doi.org/10.1016/j.yexcr.2019.04.028

Draca D, Mijatović S, Krajnović T, Bogdanović Pristov J, Dukic T, Kaluderović GN, Wessjohann LA, Maksimović-Ivanić D. The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model. in Experimental Cell Research. 2019;380(2):159-170.
doi:10.1016/j.yexcr.2019.04.028 .

Draca, Dijana, Mijatović, Sanja, Krajnović, Tamara, Bogdanović Pristov, Jelena, Dukic, Tatjana, Kaluderović, Goran N., Wessjohann, Ludger A., Maksimović-Ivanić, Danijela, "The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model" in Experimental Cell Research, 380, no. 2 (2019):159-170,
https://doi.org/10.1016/j.yexcr.2019.04.028 . .