Herein, upgraded chloroquine (CQ) derivatives capable of overcoming Plasmodium resistance and, at the same time, suppressing excessive immune response and risk of concurrent bacteremia were developed. Twelve new ferrocene-CQ hybrids tethered with a small azathia heterocycle (1,3-thiazolidin-4-one, 1,3-thiazinan-4-one, or 5-methyl-1,3-thiazolidin-4-one) were synthesized and fully characterized. All hybrids were evaluated for their in vitro antiplasmodial, antimicrobial, and immunomodulatory activities. Additional assays were performed on selected hybrids to gain insights into their mode of action. Although only hybrid 4a was more potent than the parent drug toward CQ-resistant Dd2 Plasmodium falciparum strain, several other hybrids (such as 6b, 6c, and 6d) manifested substantially improved antimicrobial and immunomodulatory properties. Interesting structure-activity relationship data were obtained, hinting at future research for the development of new multitarget chemotherapies for mala...ria and other infectious diseases complicated by drug resistance, bacterial co-infection, and immune-driven pathology issues.
Source:
Journal of Medicinal Chemistry, 2023, 66, 3, 2084-2101
TY - JOUR
AU - Aksić, Jelena
AU - Genčić, Marija
AU - Stojanović, Nikola
AU - Radulović, Niko
AU - Zlatković, Dragan
AU - Dimitrijević, Marina
AU - Stojanović-Radić, Zorica
AU - Srbljanović, Jelena
AU - Štajner, Tijana
AU - Jovanović, Ljiljana
PY - 2023
UR - http://rimi.imi.bg.ac.rs/handle/123456789/1301
AB - Herein, upgraded chloroquine (CQ) derivatives capable of overcoming Plasmodium resistance and, at the same time, suppressing excessive immune response and risk of concurrent bacteremia were developed. Twelve new ferrocene-CQ hybrids tethered with a small azathia heterocycle (1,3-thiazolidin-4-one, 1,3-thiazinan-4-one, or 5-methyl-1,3-thiazolidin-4-one) were synthesized and fully characterized. All hybrids were evaluated for their in vitro antiplasmodial, antimicrobial, and immunomodulatory activities. Additional assays were performed on selected hybrids to gain insights into their mode of action. Although only hybrid 4a was more potent than the parent drug toward CQ-resistant Dd2 Plasmodium falciparum strain, several other hybrids (such as 6b, 6c, and 6d) manifested substantially improved antimicrobial and immunomodulatory properties. Interesting structure-activity relationship data were obtained, hinting at future research for the development of new multitarget chemotherapies for malaria and other infectious diseases complicated by drug resistance, bacterial co-infection, and immune-driven pathology issues.
T2 - Journal of Medicinal Chemistry
T1 - New Iron Twist to Chloroquine─Upgrading Antimalarials with Immunomodulatory and Antimicrobial Features
EP - 2101
IS - 3
SP - 2084
VL - 66
DO - 10.1021/acs.jmedchem.2c01851
ER -
@article{
author = "Aksić, Jelena and Genčić, Marija and Stojanović, Nikola and Radulović, Niko and Zlatković, Dragan and Dimitrijević, Marina and Stojanović-Radić, Zorica and Srbljanović, Jelena and Štajner, Tijana and Jovanović, Ljiljana",
year = "2023",
abstract = "Herein, upgraded chloroquine (CQ) derivatives capable of overcoming Plasmodium resistance and, at the same time, suppressing excessive immune response and risk of concurrent bacteremia were developed. Twelve new ferrocene-CQ hybrids tethered with a small azathia heterocycle (1,3-thiazolidin-4-one, 1,3-thiazinan-4-one, or 5-methyl-1,3-thiazolidin-4-one) were synthesized and fully characterized. All hybrids were evaluated for their in vitro antiplasmodial, antimicrobial, and immunomodulatory activities. Additional assays were performed on selected hybrids to gain insights into their mode of action. Although only hybrid 4a was more potent than the parent drug toward CQ-resistant Dd2 Plasmodium falciparum strain, several other hybrids (such as 6b, 6c, and 6d) manifested substantially improved antimicrobial and immunomodulatory properties. Interesting structure-activity relationship data were obtained, hinting at future research for the development of new multitarget chemotherapies for malaria and other infectious diseases complicated by drug resistance, bacterial co-infection, and immune-driven pathology issues.",
journal = "Journal of Medicinal Chemistry",
title = "New Iron Twist to Chloroquine─Upgrading Antimalarials with Immunomodulatory and Antimicrobial Features",
pages = "2101-2084",
number = "3",
volume = "66",
doi = "10.1021/acs.jmedchem.2c01851"
}
Aksić, J., Genčić, M., Stojanović, N., Radulović, N., Zlatković, D., Dimitrijević, M., Stojanović-Radić, Z., Srbljanović, J., Štajner, T.,& Jovanović, L.. (2023). New Iron Twist to Chloroquine─Upgrading Antimalarials with Immunomodulatory and Antimicrobial Features. in Journal of Medicinal Chemistry, 66(3), 2084-2101.
https://doi.org/10.1021/acs.jmedchem.2c01851
Aksić J, Genčić M, Stojanović N, Radulović N, Zlatković D, Dimitrijević M, Stojanović-Radić Z, Srbljanović J, Štajner T, Jovanović L. New Iron Twist to Chloroquine─Upgrading Antimalarials with Immunomodulatory and Antimicrobial Features. in Journal of Medicinal Chemistry. 2023;66(3):2084-2101.
doi:10.1021/acs.jmedchem.2c01851 .
Aksić, Jelena, Genčić, Marija, Stojanović, Nikola, Radulović, Niko, Zlatković, Dragan, Dimitrijević, Marina, Stojanović-Radić, Zorica, Srbljanović, Jelena, Štajner, Tijana, Jovanović, Ljiljana, "New Iron Twist to Chloroquine─Upgrading Antimalarials with Immunomodulatory and Antimicrobial Features" in Journal of Medicinal Chemistry, 66, no. 3 (2023):2084-2101,
https://doi.org/10.1021/acs.jmedchem.2c01851 . .
