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  - Radulović, Niko S.
AU  - Mladenović, Marko Z.
AU  - Blagojević, Polina D.
AU  - Stojanović-Radić, Zorica Z.
AU  - Ilić-Tomić, Tatjana
AU  - Šenerović, Lidija
AU  - Nikodinović-Runić, Jasmina
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/694
AB  - To determine the exact structure of previously tentatively identified minor essential-oil constituents of a Chamomile species (Antemis segetalis Ten. (Asteraceae)), we have synthesized a small combinatorial library of 54 regioisomeric allylmethoxyphenyl pentanoates and 2-pentenoates (49 completely new compounds). GC-MS in combination with 1D- and 2D-NMR analyses of the library compounds provided unambiguous data that led to a straightforward identification of the mentioned A. segetalis constituents as eugenyl angelate, 2-methylbutanoate and 3-methylbutanoate (0.21, 0.22, and 0.13 mg/100 g of fresh plant material, respectively). To assess the safety and potential beneficial pharmacological uses of these naturally occurring esters and several other library compounds (these were tested to provide relevant data for a SAR (structure-activity relationship) analysis), we have studied the effect of these compounds in several models of toxicity (acute toxicity against Artemia sauna, cytotoxicity against two cell lines (fibroblast and melanoma)), as well as their acetylcholinesterase inhibitory and antibacterial activities. Anthemis segetalis constituents showed low to moderate activity in all tests. The obtained results suggest that the intake of these compounds in naturally available amounts, on their own, would probably not represent a risk to human health but the possible adverse interactions with the plant matrix should not be neglected.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Food and Chemical Toxicology
T1  - Toxic essential oils. Part III: Identification and biological activity of new allylmethoxyphenyl esters from a Chamomile species (Anthemis segetalis Ten.)
EP  - 565
SP  - 554
VL  - 62
DO  - 10.1016/j.fct.2013.09.017
ER  - 

@article{
author = "Radulović, Niko S. and Mladenović, Marko Z. and Blagojević, Polina D. and Stojanović-Radić, Zorica Z. and Ilić-Tomić, Tatjana and Šenerović, Lidija and Nikodinović-Runić, Jasmina",
year = "2013",
abstract = "To determine the exact structure of previously tentatively identified minor essential-oil constituents of a Chamomile species (Antemis segetalis Ten. (Asteraceae)), we have synthesized a small combinatorial library of 54 regioisomeric allylmethoxyphenyl pentanoates and 2-pentenoates (49 completely new compounds). GC-MS in combination with 1D- and 2D-NMR analyses of the library compounds provided unambiguous data that led to a straightforward identification of the mentioned A. segetalis constituents as eugenyl angelate, 2-methylbutanoate and 3-methylbutanoate (0.21, 0.22, and 0.13 mg/100 g of fresh plant material, respectively). To assess the safety and potential beneficial pharmacological uses of these naturally occurring esters and several other library compounds (these were tested to provide relevant data for a SAR (structure-activity relationship) analysis), we have studied the effect of these compounds in several models of toxicity (acute toxicity against Artemia sauna, cytotoxicity against two cell lines (fibroblast and melanoma)), as well as their acetylcholinesterase inhibitory and antibacterial activities. Anthemis segetalis constituents showed low to moderate activity in all tests. The obtained results suggest that the intake of these compounds in naturally available amounts, on their own, would probably not represent a risk to human health but the possible adverse interactions with the plant matrix should not be neglected.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Food and Chemical Toxicology",
title = "Toxic essential oils. Part III: Identification and biological activity of new allylmethoxyphenyl esters from a Chamomile species (Anthemis segetalis Ten.)",
pages = "565-554",
volume = "62",
doi = "10.1016/j.fct.2013.09.017"
}

Radulović, N. S., Mladenović, M. Z., Blagojević, P. D., Stojanović-Radić, Z. Z., Ilić-Tomić, T., Šenerović, L.,& Nikodinović-Runić, J.. (2013). Toxic essential oils. Part III: Identification and biological activity of new allylmethoxyphenyl esters from a Chamomile species (Anthemis segetalis Ten.). in Food and Chemical Toxicology
Pergamon-Elsevier Science Ltd, Oxford., 62, 554-565.
https://doi.org/10.1016/j.fct.2013.09.017

Radulović NS, Mladenović MZ, Blagojević PD, Stojanović-Radić ZZ, Ilić-Tomić T, Šenerović L, Nikodinović-Runić J. Toxic essential oils. Part III: Identification and biological activity of new allylmethoxyphenyl esters from a Chamomile species (Anthemis segetalis Ten.). in Food and Chemical Toxicology. 2013;62:554-565.
doi:10.1016/j.fct.2013.09.017 .

Radulović, Niko S., Mladenović, Marko Z., Blagojević, Polina D., Stojanović-Radić, Zorica Z., Ilić-Tomić, Tatjana, Šenerović, Lidija, Nikodinović-Runić, Jasmina, "Toxic essential oils. Part III: Identification and biological activity of new allylmethoxyphenyl esters from a Chamomile species (Anthemis segetalis Ten.)" in Food and Chemical Toxicology, 62 (2013):554-565,
https://doi.org/10.1016/j.fct.2013.09.017 . .