TY  - JOUR
AU  - Aksić, Jelena
AU  - Genčić, Marija
AU  - Radulović, Niko
AU  - Dimitrijević, Marina
AU  - Stojanović-Radić, Zorica
AU  - Ilić Tomić, Tatjana
AU  - Rodić, Marko
PY  - 2023
UR  - https://www.sciencedirect.com/science/article/pii/S0045206823003693
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2068
AB  - To improve the antiproliferative effect of ALC67 (diastereomeric mixture of ethyl 2-phenyl-3-propioloyl-1,3-thiazolidine-4-carboxylate), its structure was modified via (i) bioisosteric substitution of the phenyl ring by the ferrocene unit and (ii) replacing the propiolamide side-chain in ACL67 with other acyl groups having differing electrophilicities. In this way, a small library of methyl N-acyl-2-ferrocenyl-1,3-thiazolidine-4-carboxylates (13 compounds in total) was created and characterized by spectral and crystallographic means. The last N-acylation step was highly diastereoselective toward the cis-diastereomer. In solution, most of the obtained compounds existed as a mixture of two rotamers and displayed a preference for the syn-orientation around the CN bond. A twisted 5T4 envelope conformation was adopted by the derivative containing the N-phenoxyacetyl group in the crystalline state. Two derivatives with chloroacetyl and bromoacetyl groups in the N-3 side chain were cytotoxic to fibroblasts and hepatocellular cancer cells in the low micromolar range (IC50(MRC5) = 9.0 and 11.8 μM, respectively, and IC50(HepG2) = 10.6 and 18.4 μM, respectively) causing an effect similar to the lead compound (IC50(HepG2) = 10.0 μM) and cisplatin (IC50(MRC5) = 4.0 μM and IC50(HepG2) = 7.7 μM). Several derivatives also manifested modest antimicrobial effects against the studied microbial strains (MICs in the range from 0.44 to 4.0 μmol/mL). Our findings demonstrated that the introduction of a ferrocene core facilitated the preparation of optically pure analogs of ALC67 and that the cytotoxicity of compounds may be enhanced by adding proper electrophilic centers to the N-acyl side-chain.
T2  - Bioorganic Chemistry
T1  - Bioisosteric ferrocenyl 1,3-thiazolidine-4-carboxylic acid derivatives: In vitro antiproliferative and antimicrobial evaluations
SP  - 106708
VL  - 139
DO  - 10.1016/j.bioorg.2023.106708
ER  - 

@article{
author = "Aksić, Jelena and Genčić, Marija and Radulović, Niko and Dimitrijević, Marina and Stojanović-Radić, Zorica and Ilić Tomić, Tatjana and Rodić, Marko",
year = "2023",
abstract = "To improve the antiproliferative effect of ALC67 (diastereomeric mixture of ethyl 2-phenyl-3-propioloyl-1,3-thiazolidine-4-carboxylate), its structure was modified via (i) bioisosteric substitution of the phenyl ring by the ferrocene unit and (ii) replacing the propiolamide side-chain in ACL67 with other acyl groups having differing electrophilicities. In this way, a small library of methyl N-acyl-2-ferrocenyl-1,3-thiazolidine-4-carboxylates (13 compounds in total) was created and characterized by spectral and crystallographic means. The last N-acylation step was highly diastereoselective toward the cis-diastereomer. In solution, most of the obtained compounds existed as a mixture of two rotamers and displayed a preference for the syn-orientation around the CN bond. A twisted 5T4 envelope conformation was adopted by the derivative containing the N-phenoxyacetyl group in the crystalline state. Two derivatives with chloroacetyl and bromoacetyl groups in the N-3 side chain were cytotoxic to fibroblasts and hepatocellular cancer cells in the low micromolar range (IC50(MRC5) = 9.0 and 11.8 μM, respectively, and IC50(HepG2) = 10.6 and 18.4 μM, respectively) causing an effect similar to the lead compound (IC50(HepG2) = 10.0 μM) and cisplatin (IC50(MRC5) = 4.0 μM and IC50(HepG2) = 7.7 μM). Several derivatives also manifested modest antimicrobial effects against the studied microbial strains (MICs in the range from 0.44 to 4.0 μmol/mL). Our findings demonstrated that the introduction of a ferrocene core facilitated the preparation of optically pure analogs of ALC67 and that the cytotoxicity of compounds may be enhanced by adding proper electrophilic centers to the N-acyl side-chain.",
journal = "Bioorganic Chemistry",
title = "Bioisosteric ferrocenyl 1,3-thiazolidine-4-carboxylic acid derivatives: In vitro antiproliferative and antimicrobial evaluations",
pages = "106708",
volume = "139",
doi = "10.1016/j.bioorg.2023.106708"
}

Aksić, J., Genčić, M., Radulović, N., Dimitrijević, M., Stojanović-Radić, Z., Ilić Tomić, T.,& Rodić, M.. (2023). Bioisosteric ferrocenyl 1,3-thiazolidine-4-carboxylic acid derivatives: In vitro antiproliferative and antimicrobial evaluations. in Bioorganic Chemistry, 139, 106708.
https://doi.org/10.1016/j.bioorg.2023.106708

Aksić J, Genčić M, Radulović N, Dimitrijević M, Stojanović-Radić Z, Ilić Tomić T, Rodić M. Bioisosteric ferrocenyl 1,3-thiazolidine-4-carboxylic acid derivatives: In vitro antiproliferative and antimicrobial evaluations. in Bioorganic Chemistry. 2023;139:106708.
doi:10.1016/j.bioorg.2023.106708 .

Aksić, Jelena, Genčić, Marija, Radulović, Niko, Dimitrijević, Marina, Stojanović-Radić, Zorica, Ilić Tomić, Tatjana, Rodić, Marko, "Bioisosteric ferrocenyl 1,3-thiazolidine-4-carboxylic acid derivatives: In vitro antiproliferative and antimicrobial evaluations" in Bioorganic Chemistry, 139 (2023):106708,
https://doi.org/10.1016/j.bioorg.2023.106708 . .

TY  - JOUR
AU  - Svircev, Milos
AU  - Popsavin, Mirjana
AU  - Pavić, Aleksandar
AU  - Vasiljević, Branka
AU  - Rodić, Marko V.
AU  - Đokić, Sanja
AU  - Kesić, Jelena
AU  - Sreco Zelenović, Bojana
AU  - Popsavin, Velimir
AU  - Kojić, Vesna
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1561
AB  - The synthesis of several new goniofufurone bioisosteres was achieved in which the phenyl residue was replaced by a thiazole ring. The key steps of the synthesis included the initial condensation of cyanohydrin benzoates with cysteine ethyl ester hydrochloride, followed by the subsequent reaction of resulting C-4 ' epimeric thiazolines with DBU, to introduce 5-deoxy functionality and to elaborate the thiazole ring in one step. Synthesized compounds showed potent growth inhibitory effects against selected human tumour cell lines, especially bioisostere 4, which in the culture of MCF-7 cells displayed the highest activity (IC50 = 0.19 nM) of all compounds under evaluation. This molecule exhibited 64474-fold higher antiproliferative activity than lead 2 and was1053-fold more active than the commercial antitumour agent doxorubicin in the culture of MCF-7 cells. The structural features of the tested compounds responsible for their antiproliferative activity have been identified by preliminary SAR analysis. The toxicity of the most active compound 4 was assessed by an in vivo experiment in a zebrafish model (Danio rerio), whereupon it was found non-toxic at any of the tested concentrations up to 125 mu M.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Bioorganic Chemistry
T1  - Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity
VL  - 121
DO  - 10.1016/j.bioorg.2022.105691
ER  - 

@article{
author = "Svircev, Milos and Popsavin, Mirjana and Pavić, Aleksandar and Vasiljević, Branka and Rodić, Marko V. and Đokić, Sanja and Kesić, Jelena and Sreco Zelenović, Bojana and Popsavin, Velimir and Kojić, Vesna",
year = "2022",
abstract = "The synthesis of several new goniofufurone bioisosteres was achieved in which the phenyl residue was replaced by a thiazole ring. The key steps of the synthesis included the initial condensation of cyanohydrin benzoates with cysteine ethyl ester hydrochloride, followed by the subsequent reaction of resulting C-4 ' epimeric thiazolines with DBU, to introduce 5-deoxy functionality and to elaborate the thiazole ring in one step. Synthesized compounds showed potent growth inhibitory effects against selected human tumour cell lines, especially bioisostere 4, which in the culture of MCF-7 cells displayed the highest activity (IC50 = 0.19 nM) of all compounds under evaluation. This molecule exhibited 64474-fold higher antiproliferative activity than lead 2 and was1053-fold more active than the commercial antitumour agent doxorubicin in the culture of MCF-7 cells. The structural features of the tested compounds responsible for their antiproliferative activity have been identified by preliminary SAR analysis. The toxicity of the most active compound 4 was assessed by an in vivo experiment in a zebrafish model (Danio rerio), whereupon it was found non-toxic at any of the tested concentrations up to 125 mu M.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Bioorganic Chemistry",
title = "Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity",
volume = "121",
doi = "10.1016/j.bioorg.2022.105691"
}

Svircev, M., Popsavin, M., Pavić, A., Vasiljević, B., Rodić, M. V., Đokić, S., Kesić, J., Sreco Zelenović, B., Popsavin, V.,& Kojić, V.. (2022). Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity. in Bioorganic Chemistry
Academic Press Inc Elsevier Science, San Diego., 121.
https://doi.org/10.1016/j.bioorg.2022.105691

Svircev M, Popsavin M, Pavić A, Vasiljević B, Rodić MV, Đokić S, Kesić J, Sreco Zelenović B, Popsavin V, Kojić V. Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity. in Bioorganic Chemistry. 2022;121.
doi:10.1016/j.bioorg.2022.105691 .

Svircev, Milos, Popsavin, Mirjana, Pavić, Aleksandar, Vasiljević, Branka, Rodić, Marko V., Đokić, Sanja, Kesić, Jelena, Sreco Zelenović, Bojana, Popsavin, Velimir, Kojić, Vesna, "Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity" in Bioorganic Chemistry, 121 (2022),
https://doi.org/10.1016/j.bioorg.2022.105691 . .

TY  - JOUR
AU  - Stanić, Petar B.
AU  - Rodić, Marko, V
AU  - Soldatović, Tanja, V
AU  - Pavić, Aleksandar
AU  - Radaković, Nataša
AU  - Smit, Biljana M.
AU  - Živković, Marija D.
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1317
AB  - The 3-arylidene-2-thiohydantoin derivative, 3-[(2-hydroxybenzylidene)amino]-2-thioxoimidazolidin-4-one, was synthesized in a two-step condensation reaction of 2-hydroxybenzaldehyde, thiosemicarbazide and ethyl chloroacetate. The ligand was structurally characterized by NMR and IR spectroscopy, as well as by elemental analysis. In the reaction of the well-known polymeric trans-[CuCl2(DMSO)(2)](n) complex with the polydentate thiohydantoin type ligand, instead of the corresponding copper thiohydantoin complex, unexpectedly, the dinuclear cis-[{CuCl(DMSO)(2)}(mu-Cl)](2) complex (1) was formed predominantly as the final stable product. The structure of the complex 1 was confirmed by single crystal X-ray diffraction analysis. The cis-complex is obtained through assisted isomerization of the trans-form, in which the thiohydantoin derivative has a crucial role.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - Reaction of a 3-aryilidene-2-thiohydantoin derivative with polymeric trans-[CuCl2(DMSO)(2)](n) complex: unexpected isomerization to dinuclear cis-[{CuCl(DMSO)(2)}(mu-Cl)](2)
EP  - 1603
IS  - 12
SP  - 1591
VL  - 85
DO  - 10.2298/JSC200917060S
ER  - 

@article{
author = "Stanić, Petar B. and Rodić, Marko, V and Soldatović, Tanja, V and Pavić, Aleksandar and Radaković, Nataša and Smit, Biljana M. and Živković, Marija D.",
year = "2020",
abstract = "The 3-arylidene-2-thiohydantoin derivative, 3-[(2-hydroxybenzylidene)amino]-2-thioxoimidazolidin-4-one, was synthesized in a two-step condensation reaction of 2-hydroxybenzaldehyde, thiosemicarbazide and ethyl chloroacetate. The ligand was structurally characterized by NMR and IR spectroscopy, as well as by elemental analysis. In the reaction of the well-known polymeric trans-[CuCl2(DMSO)(2)](n) complex with the polydentate thiohydantoin type ligand, instead of the corresponding copper thiohydantoin complex, unexpectedly, the dinuclear cis-[{CuCl(DMSO)(2)}(mu-Cl)](2) complex (1) was formed predominantly as the final stable product. The structure of the complex 1 was confirmed by single crystal X-ray diffraction analysis. The cis-complex is obtained through assisted isomerization of the trans-form, in which the thiohydantoin derivative has a crucial role.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "Reaction of a 3-aryilidene-2-thiohydantoin derivative with polymeric trans-[CuCl2(DMSO)(2)](n) complex: unexpected isomerization to dinuclear cis-[{CuCl(DMSO)(2)}(mu-Cl)](2)",
pages = "1603-1591",
number = "12",
volume = "85",
doi = "10.2298/JSC200917060S"
}

Stanić, P. B., Rodić, M. V., Soldatović, T. V., Pavić, A., Radaković, N., Smit, B. M.,& Živković, M. D.. (2020). Reaction of a 3-aryilidene-2-thiohydantoin derivative with polymeric trans-[CuCl2(DMSO)(2)](n) complex: unexpected isomerization to dinuclear cis-[{CuCl(DMSO)(2)}(mu-Cl)](2). in Journal of the Serbian Chemical Society
Srpsko hemijsko društvo, Beograd., 85(12), 1591-1603.
https://doi.org/10.2298/JSC200917060S

Stanić PB, Rodić MV, Soldatović TV, Pavić A, Radaković N, Smit BM, Živković MD. Reaction of a 3-aryilidene-2-thiohydantoin derivative with polymeric trans-[CuCl2(DMSO)(2)](n) complex: unexpected isomerization to dinuclear cis-[{CuCl(DMSO)(2)}(mu-Cl)](2). in Journal of the Serbian Chemical Society. 2020;85(12):1591-1603.
doi:10.2298/JSC200917060S .

Stanić, Petar B., Rodić, Marko, V, Soldatović, Tanja, V, Pavić, Aleksandar, Radaković, Nataša, Smit, Biljana M., Živković, Marija D., "Reaction of a 3-aryilidene-2-thiohydantoin derivative with polymeric trans-[CuCl2(DMSO)(2)](n) complex: unexpected isomerization to dinuclear cis-[{CuCl(DMSO)(2)}(mu-Cl)](2)" in Journal of the Serbian Chemical Society, 85, no. 12 (2020):1591-1603,
https://doi.org/10.2298/JSC200917060S . .

TY  - JOUR
AU  - Gitarić, Jelena
AU  - Stanojević, Ivana M.
AU  - Rodić, Marko, V
AU  - Drasković, Nenad S.
AU  - Stevanović, Milena
AU  - Vojnović, Sandra
AU  - Djuran, Milos
AU  - Glišić, Biljana
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1352
AB  - New polynuclear manganese(II) and cadmium(II) complexes with 2,2-dimethyl-1,3-propanediamine-N,N, N',N'-tetraacetato ligand (2,2-diMe-1,3-pdta), {Ba[M(2,2-diMe-1,3-pdta)]center dot 3H(2)O}(n) (M = Mn (1) or Cd (2)) were synthesized and characterized by IR spectroscopy and single-crystal X-ray diffraction analysis. In addition, complex 2 was characterized by solution H-1 and C-13 NMR spectroscopy. Crystallographic analysis showed that 2,2-diMe-1,3-pdta ligand is hexadentately coordinated to each M(II) ion through the two nitrogen and four carboxylate oxygen atoms, whereas the one of these oxygen atoms is also involved in coordination to the second M(II) ion of the dinuclear [M-2(2,2-diMe-1,3-pdta)(2)](4-) unit in polymeric structures. Moreover, three of four carboxylic groups of 2,2-diMe-1,3-pdta ligand are additionally bonded to four Ba(II) ions, in three distinctive bridging coordination modes. Each Ba(II) ion is surrounded by ten oxygen atoms, seven belonging to carboxylate groups of 2,2-diMe-1,3-pdta, and three belonging to water molecules. The coordination environment around Mn(II) and Cd(II) ions could be assigned as a face capped octahedron, while coordination polyhedron around Ba(II) ion in these two complexes was described as a distorted sphenocorona. The antimicrobial potential of complexes 1 and 2 and corresponding metal salts used for their synthesis was evaluated against different bacterial and Candida spp. Both complexes showed selective antifungal activity against the tested Candida spp. compared to the bacterial strains, with the minimal inhibitory concentration (MIC) values in the range 3.12 - 12.50 mu M. Moreover, complex 1 caused the slightly decrease of hyphae length, while no significant influence on hyphal length of complex 2 was observed. With aim to assess the therapeutic profile of the complexes, their cytotoxicity was evaluated against the normal human lung fibroblast cell line (MRC-5).
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Polyhedron
T1  - Structural characterization and biological evaluation of polynuclear Mn (II) and Cd(II) complexes with 2,2-dimethyl-1,3-propanediamine-N,N,N ', N '-tetraacetate. The influence of ligand structure and counter cation on the complex nuclearity
VL  - 188
DO  - 10.1016/j.poly.2020.114688
ER  - 

@article{
author = "Gitarić, Jelena and Stanojević, Ivana M. and Rodić, Marko, V and Drasković, Nenad S. and Stevanović, Milena and Vojnović, Sandra and Djuran, Milos and Glišić, Biljana",
year = "2020",
abstract = "New polynuclear manganese(II) and cadmium(II) complexes with 2,2-dimethyl-1,3-propanediamine-N,N, N',N'-tetraacetato ligand (2,2-diMe-1,3-pdta), {Ba[M(2,2-diMe-1,3-pdta)]center dot 3H(2)O}(n) (M = Mn (1) or Cd (2)) were synthesized and characterized by IR spectroscopy and single-crystal X-ray diffraction analysis. In addition, complex 2 was characterized by solution H-1 and C-13 NMR spectroscopy. Crystallographic analysis showed that 2,2-diMe-1,3-pdta ligand is hexadentately coordinated to each M(II) ion through the two nitrogen and four carboxylate oxygen atoms, whereas the one of these oxygen atoms is also involved in coordination to the second M(II) ion of the dinuclear [M-2(2,2-diMe-1,3-pdta)(2)](4-) unit in polymeric structures. Moreover, three of four carboxylic groups of 2,2-diMe-1,3-pdta ligand are additionally bonded to four Ba(II) ions, in three distinctive bridging coordination modes. Each Ba(II) ion is surrounded by ten oxygen atoms, seven belonging to carboxylate groups of 2,2-diMe-1,3-pdta, and three belonging to water molecules. The coordination environment around Mn(II) and Cd(II) ions could be assigned as a face capped octahedron, while coordination polyhedron around Ba(II) ion in these two complexes was described as a distorted sphenocorona. The antimicrobial potential of complexes 1 and 2 and corresponding metal salts used for their synthesis was evaluated against different bacterial and Candida spp. Both complexes showed selective antifungal activity against the tested Candida spp. compared to the bacterial strains, with the minimal inhibitory concentration (MIC) values in the range 3.12 - 12.50 mu M. Moreover, complex 1 caused the slightly decrease of hyphae length, while no significant influence on hyphal length of complex 2 was observed. With aim to assess the therapeutic profile of the complexes, their cytotoxicity was evaluated against the normal human lung fibroblast cell line (MRC-5).",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Polyhedron",
title = "Structural characterization and biological evaluation of polynuclear Mn (II) and Cd(II) complexes with 2,2-dimethyl-1,3-propanediamine-N,N,N ', N '-tetraacetate. The influence of ligand structure and counter cation on the complex nuclearity",
volume = "188",
doi = "10.1016/j.poly.2020.114688"
}

Gitarić, J., Stanojević, I. M., Rodić, M. V., Drasković, N. S., Stevanović, M., Vojnović, S., Djuran, M.,& Glišić, B.. (2020). Structural characterization and biological evaluation of polynuclear Mn (II) and Cd(II) complexes with 2,2-dimethyl-1,3-propanediamine-N,N,N ', N '-tetraacetate. The influence of ligand structure and counter cation on the complex nuclearity. in Polyhedron
Pergamon-Elsevier Science Ltd, Oxford., 188.
https://doi.org/10.1016/j.poly.2020.114688

Gitarić J, Stanojević IM, Rodić MV, Drasković NS, Stevanović M, Vojnović S, Djuran M, Glišić B. Structural characterization and biological evaluation of polynuclear Mn (II) and Cd(II) complexes with 2,2-dimethyl-1,3-propanediamine-N,N,N ', N '-tetraacetate. The influence of ligand structure and counter cation on the complex nuclearity. in Polyhedron. 2020;188.
doi:10.1016/j.poly.2020.114688 .

Gitarić, Jelena, Stanojević, Ivana M., Rodić, Marko, V, Drasković, Nenad S., Stevanović, Milena, Vojnović, Sandra, Djuran, Milos, Glišić, Biljana, "Structural characterization and biological evaluation of polynuclear Mn (II) and Cd(II) complexes with 2,2-dimethyl-1,3-propanediamine-N,N,N ', N '-tetraacetate. The influence of ligand structure and counter cation on the complex nuclearity" in Polyhedron, 188 (2020),
https://doi.org/10.1016/j.poly.2020.114688 . .