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 . .