Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis
Апстракт
The chronic inflammatory process is associated with the development and progression of many diseases such as cancer, arthritis, autoimmune diseases, etc. Dual COX-2 and 5-LOX inhibitors have been developed to provide more potent anti-inflammatory agents with a better safety profile [1].
Nineteen newly synthesised potential dual COX-2 and 5-LOX inhibitors [2] were selected and their retention properties were tested in different RP-HPLC systems. RP-HPLC analysis was performed using a C18, a cyano and an amino column. The mobile phases were binary combinations of acetonitrile and phosphate buffer (pH 5.5 and pH 7.4) as well as methanol and phosphate buffer (pH 5.5 and pH 7.4) in different ratios. The amino column proved to be inadequate as the tested compounds were not retained on it.
According to preliminary results, methanol was not suitable as an organic modifier in the mobile phase as the retention time of the compounds was increased several times compared to acetonitrile. Acetonitr...ile was
chosen as the organic modifier. The logarithmic values of the retention factors (logk) were calculated for each sample and plotted with the percentage of organic modifier in the mobile phase. The chromatography parameters logkw, a and ϕ0 were determined according to equation (1) and equation (2) (S-percentage of
organic modifier in the mobile phase).
Logk = logkw + aS (1)
ϕ0 = - logkw/a (2)
On C18 and cyano columns, seven compounds (1A, 1G, 1ME, 1PE, and 2D) had no retention properties, which is consistent with their very low logD values, while three (1F, 1H, and QSAR17) compounds were outlayers. Systems consisting of C18 and cyano columns (on both pH 5.5 and 7.4) showed good correlation coefficients between the chromatography parameters logkw, a, and ϕ0 and the logD values determined with MarvinSketch. The most suitable system consisted of a C18 column, acetonitrile, and phosphate buffer pH 7.4, as it had the highest correlation coefficient between the chromatography parameter logkw and the logD value (R2=0.9023) (3 compounds were discarded).
Извор:
MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts, 2023, 116-116Издавач:
- Aristotle University, Greece
- Paul Ehrlich MedChem EuroPhD Network
Институција/група
PharmacyTY - CONF AU - Bošković, Jelena AU - Crevar, Milkica AU - Čudina, Olivera AU - Dobričić, Vladimir PY - 2023 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5453 AB - The chronic inflammatory process is associated with the development and progression of many diseases such as cancer, arthritis, autoimmune diseases, etc. Dual COX-2 and 5-LOX inhibitors have been developed to provide more potent anti-inflammatory agents with a better safety profile [1]. Nineteen newly synthesised potential dual COX-2 and 5-LOX inhibitors [2] were selected and their retention properties were tested in different RP-HPLC systems. RP-HPLC analysis was performed using a C18, a cyano and an amino column. The mobile phases were binary combinations of acetonitrile and phosphate buffer (pH 5.5 and pH 7.4) as well as methanol and phosphate buffer (pH 5.5 and pH 7.4) in different ratios. The amino column proved to be inadequate as the tested compounds were not retained on it. According to preliminary results, methanol was not suitable as an organic modifier in the mobile phase as the retention time of the compounds was increased several times compared to acetonitrile. Acetonitrile was chosen as the organic modifier. The logarithmic values of the retention factors (logk) were calculated for each sample and plotted with the percentage of organic modifier in the mobile phase. The chromatography parameters logkw, a and ϕ0 were determined according to equation (1) and equation (2) (S-percentage of organic modifier in the mobile phase). Logk = logkw + aS (1) ϕ0 = - logkw/a (2) On C18 and cyano columns, seven compounds (1A, 1G, 1ME, 1PE, and 2D) had no retention properties, which is consistent with their very low logD values, while three (1F, 1H, and QSAR17) compounds were outlayers. Systems consisting of C18 and cyano columns (on both pH 5.5 and 7.4) showed good correlation coefficients between the chromatography parameters logkw, a, and ϕ0 and the logD values determined with MarvinSketch. The most suitable system consisted of a C18 column, acetonitrile, and phosphate buffer pH 7.4, as it had the highest correlation coefficient between the chromatography parameter logkw and the logD value (R2=0.9023) (3 compounds were discarded). PB - Aristotle University, Greece PB - Paul Ehrlich MedChem EuroPhD Network C3 - MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts T1 - Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis SP - 116 EP - 116 UR - https://hdl.handle.net/21.15107/rcub_farfar_5453 ER -
@conference{ author = "Bošković, Jelena and Crevar, Milkica and Čudina, Olivera and Dobričić, Vladimir", year = "2023", abstract = "The chronic inflammatory process is associated with the development and progression of many diseases such as cancer, arthritis, autoimmune diseases, etc. Dual COX-2 and 5-LOX inhibitors have been developed to provide more potent anti-inflammatory agents with a better safety profile [1]. Nineteen newly synthesised potential dual COX-2 and 5-LOX inhibitors [2] were selected and their retention properties were tested in different RP-HPLC systems. RP-HPLC analysis was performed using a C18, a cyano and an amino column. The mobile phases were binary combinations of acetonitrile and phosphate buffer (pH 5.5 and pH 7.4) as well as methanol and phosphate buffer (pH 5.5 and pH 7.4) in different ratios. The amino column proved to be inadequate as the tested compounds were not retained on it. According to preliminary results, methanol was not suitable as an organic modifier in the mobile phase as the retention time of the compounds was increased several times compared to acetonitrile. Acetonitrile was chosen as the organic modifier. The logarithmic values of the retention factors (logk) were calculated for each sample and plotted with the percentage of organic modifier in the mobile phase. The chromatography parameters logkw, a and ϕ0 were determined according to equation (1) and equation (2) (S-percentage of organic modifier in the mobile phase). Logk = logkw + aS (1) ϕ0 = - logkw/a (2) On C18 and cyano columns, seven compounds (1A, 1G, 1ME, 1PE, and 2D) had no retention properties, which is consistent with their very low logD values, while three (1F, 1H, and QSAR17) compounds were outlayers. Systems consisting of C18 and cyano columns (on both pH 5.5 and 7.4) showed good correlation coefficients between the chromatography parameters logkw, a, and ϕ0 and the logD values determined with MarvinSketch. The most suitable system consisted of a C18 column, acetonitrile, and phosphate buffer pH 7.4, as it had the highest correlation coefficient between the chromatography parameter logkw and the logD value (R2=0.9023) (3 compounds were discarded).", publisher = "Aristotle University, Greece, Paul Ehrlich MedChem EuroPhD Network", journal = "MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts", title = "Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis", pages = "116-116", url = "https://hdl.handle.net/21.15107/rcub_farfar_5453" }
Bošković, J., Crevar, M., Čudina, O.,& Dobričić, V.. (2023). Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis. in MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts Aristotle University, Greece., 116-116. https://hdl.handle.net/21.15107/rcub_farfar_5453
Bošković J, Crevar M, Čudina O, Dobričić V. Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis. in MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts. 2023;:116-116. https://hdl.handle.net/21.15107/rcub_farfar_5453 .
Bošković, Jelena, Crevar, Milkica, Čudina, Olivera, Dobričić, Vladimir, "Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis" in MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts (2023):116-116, https://hdl.handle.net/21.15107/rcub_farfar_5453 .