Bioisosteric ferrocenyl 1,3-thiazolidine-4-carboxylic acid derivatives: In vitro antiproliferative and antimicrobial evaluations
Само за регистроване кориснике
2023
Аутори
Aksić, JelenaGenčić, Marija
Radulović, Niko
Dimitrijević, Marina
Stojanović-Radić, Zorica
Ilić Tomić, Tatjana
Rodić, Marko
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
1,3-Thiazolidine-4-carboxylic acid / Antimicrobial activity / Cytotoxicity / Ferrocenyl analogs / Highly diastereoselective synthesis / Solution and solid-state conformationИзвор:
Bioorganic Chemistry, 2023, 139, 106708-Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200124 (Универзитет у Нишу, Природно-математички факултет) (RS-MESTD-inst-2020-200124)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
URI
https://www.sciencedirect.com/science/article/pii/S0045206823003693https://imagine.imgge.bg.ac.rs/handle/123456789/2068
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - 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 . .