In the present work, a new set of N-(2-((4-(1,3-diphenyl-1H-pyrazol-4-yl)pyridine sulfonamide derivatives was synthesized. Final target compounds were tested against JNK1 and JNK2 isoforms. Compounds 8f and 8d showed the highest activity over both JNK isoforms. They showed submicromolar activity over JNK1 (IC50 0.90 µM and 0.96 µM, respectively). They also showed excellent activity over JNK2 (IC50 0.62 µM and 1.07 µM, respectively). Moreover, the final target compounds were tested over HL-60 and K-562 cell lines for assessing the in vitro anticancer activity using sorafenib as a positive control. Compound 8f showed the highest potency at IC50 values of 6.21 and 7.43 µM, respectively. Furthermore, compounds 8e and 8g exhibited strong effects on both acute leukemia cancer cell lines with IC50 values of 13.83 and 10.02 µM, respectively, as well as chronic leukemia cancer cell line with IC50 of 12.65 and 9.51 µM, respectively. Compound 8f was also tested to examine its effect on the cell cycle. Finally, a molecular docking study was conducted to understand the plausible binding modes of the most active compounds 8d and 8f within the JNK1 and JNK2 binding sites.
Development of Novel 1,3,4-Trisubstituted Pyrazole Derivatives Bearing Sulfonamide Moiety as Anticancer Agents Targeting JNK Kinases
Brogi S.;
2024-01-01
Abstract
In the present work, a new set of N-(2-((4-(1,3-diphenyl-1H-pyrazol-4-yl)pyridine sulfonamide derivatives was synthesized. Final target compounds were tested against JNK1 and JNK2 isoforms. Compounds 8f and 8d showed the highest activity over both JNK isoforms. They showed submicromolar activity over JNK1 (IC50 0.90 µM and 0.96 µM, respectively). They also showed excellent activity over JNK2 (IC50 0.62 µM and 1.07 µM, respectively). Moreover, the final target compounds were tested over HL-60 and K-562 cell lines for assessing the in vitro anticancer activity using sorafenib as a positive control. Compound 8f showed the highest potency at IC50 values of 6.21 and 7.43 µM, respectively. Furthermore, compounds 8e and 8g exhibited strong effects on both acute leukemia cancer cell lines with IC50 values of 13.83 and 10.02 µM, respectively, as well as chronic leukemia cancer cell line with IC50 of 12.65 and 9.51 µM, respectively. Compound 8f was also tested to examine its effect on the cell cycle. Finally, a molecular docking study was conducted to understand the plausible binding modes of the most active compounds 8d and 8f within the JNK1 and JNK2 binding sites.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.