Anticancer and anti-inflammatory effects of novel ethyl pyrazole derivatives having sulfonamide terminal moiety.

Autor: Abdel-Maksoud MS; Medicinal &Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre (NRC), P.O. 12622, Dokki, Giza, Egypt. Electronic address: ph_ss@hotmail.com., Nasser SA; Medicinal &Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre (NRC), P.O. 12622, Dokki, Giza, Egypt., Hassan RM; Medicinal &Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre (NRC), P.O. 12622, Dokki, Giza, Egypt., Abd-Allah WH; Pharmaceutical Chemistry Department, Collage of Pharmaceutical Science and Drug Manufacturing, Misr University for Science and Technology, P.O. 77, 6th of October City, Giza, Egypt.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Sep 16; Vol. 153, pp. 107825. Date of Electronic Publication: 2024 Sep 16.
DOI: 10.1016/j.bioorg.2024.107825
Abstrakt: In the present work, a new series of ethyl pyrazole-containing compounds with side sulphonamide moiety was designed and synthesized. The new derivatives were divided into four groups based on the linker between the sulphonamide and pyridine ring attached to position 4 of the pyrazole ring and the substitution on the phenyl ring at position 3 of the same ring. The linker could be ethyl or propyl linkers. The phenyl ring is substituted with a methoxy group or hydroxyl group at position 3. The aim compounds were tested for their JNK1, JNK2, JNK3, and BRAF(V600E) activities. Compounds 23b, 23c, and 23d showed the highest activity with nanomolar IC 50 s. The most potent compound over JNK1 was 23d with an IC 50 2 nM. While compound 23c was the most potent over JNK2 with an IC 50 57 nM. Finally, compound 23b was the most potent over JNK2 and BRAF(V600E) with IC 50 s of125 nM and 98 nM, respectively. After obtaining kinase inhibitory activity, the compounds were submitted to NCI to test their activity over different cell lines. Compound 23b showed the highest activity over most tested cell lines. In the second part of the present study, the final target compounds were tested for their anti-inflammatory effect. The anti-inflammatory effect of the new final compounds was performed by measuring their ability to inhibit inducible nitric oxide release and prostaglandin E2 production inhibition. Compound 23c showed the highest activity regarding nitric oxide release with IC 50 0.63 μM, while compound 21d had the highest activity regarding prostaglandin E2 production with IC 50 0.52 μM. The effect of the most potent compounds was tested by western blot against iNOS, COX-1, and COX-2.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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