New Iron Twist to Chloroquine─Upgrading Antimalarials with Immunomodulatory and Antimicrobial Features
Само за регистроване кориснике
2023
Аутори
Aksić, JelenaGenčić, Marija
Stojanović, Nikola
Radulović, Niko
Zlatković, Dragan
Dimitrijević, Marina
Stojanović-Radić, Zorica
Srbljanović, Jelena
Štajner, Tijana
Jovanović, Ljiljana
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Извор:
Journal of Medicinal Chemistry, 2023, 66, 3, 2084-2101Издавач:
- American Chemical Society
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 - 200113 (Универзитет у Нишу, Медицински факултет) (RS-MESTD-inst-2020-200113)
Институција/група
Institut za medicinska istraživanjaTY - 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. PB - American Chemical Society 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.", publisher = "American Chemical Society", 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 American Chemical Society., 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 . .