| Autor: |
Abdelrahman KS; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt., Hassan HA; Department of Medicinal Chemistry Faculty of Pharmacy, Minia University, Minia 61519, Egypt., Abdel-Aziz SA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, Minia 61768, Egypt., Marzouk AA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt.; National Center for Natural Products Research, School of Pharmacy, University of Missippi, Oxford, MS 38677, USA., Shams R; Emergent Bioengineering Materials Research Team, RIKEN Centre for Emergent Matter Science, RIKEN, Wako 351-0198, Saitama, Japan., Osawa K; Graduate School of Science and Engineering, Yamagata University, Yonezawa 992-8510, Yamagata, Japan., Abdel-Aziz M; Department of Medicinal Chemistry Faculty of Pharmacy, Minia University, Minia 61519, Egypt., Konno H; Graduate School of Science and Engineering, Yamagata University, Yonezawa 992-8510, Yamagata, Japan. |
| Abstrakt: |
New 1,5-diarylpyrazole oxime hybrid derivatives (scaffolds A and B ) were designed, synthesized, and then their purity was verified using a variety of spectroscopic methods. A panel of five cancer cell lines known to express EGFR and JNK-2, including human colorectal adenocarcinoma cell line DLD-1, human cervical cancer cell line Hela, human leukemia cell line K562, human pancreatic cell line SUIT-2, and human hepatocellular carcinoma cell line HepG2, were used to biologically evaluate for their in vitro cytotoxicity for all the synthesized compounds 7a - j , 8a - j , 9a - c , and 10a - c . The oxime containing compounds 8a-j and 10a-c were more active as antiproliferative agents than their non-oxime congeners 7a-j and 9a-c. Compounds 8d , 8g , 8i , and 10c inhibited EGFR with IC 50 values ranging from 8 to 21 µM when compared with sorafenib. Compound 8i inhibited JNK-2 as effectively as sorafenib, with an IC 50 of 1.0 µM. Furthermore, compound 8g showed cell cycle arrest at the G2/M phase in the cell cycle analysis of the Hela cell line, whereas compound 8i showed combined S phase and G2 phase arrest. According to docking studies, oxime hybrid compounds 8d , 8g , 8i , and 10c exhibited binding free energies ranging from -12.98 to 32.30 kcal/mol at the EGFR binding site whereas compounds 8d and 8i had binding free energies ranging from -9.16 to -12.00 kcal/mol at the JNK-2 binding site. |
