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Novel 2,6-disubstituted pyridine hydrazones: Synthesis, anticancer activity, docking studies and effects on caspase-3-mediated apoptosis.

Authors :
Şenkardeş, Sevil
Türe, Aslı
Ekrek, Sedanur
Durak, Asım Tuğrul
Abbak, Mürüvvet
Çevik, Özge
Kaşkatepe, Banu
Küçükgüzel, İlkay
Güniz Küçükgüzel, Ş
Source :
Journal of Molecular Structure. Jan2021, Vol. 1223, pN.PAG-N.PAG. 1p.
Publication Year :
2021

Abstract

• New 2,6-disubstituted pyridine hydrazone derivatives were synthesized and evaluated for anticancer activity. • 3f and 3k showed remarkable cytotoxic activity against HT-29 with IC 50 value of 6.78 and 8.88 µM, respectively. • Also, 3g showed the best cytotoxic activity against ISH with IC 50 value of 8.26 µM. • 3f, 3g and 3k caused morphological changes of tumor cells and induced apoptosis. • Molecular docking was performed into BRAF kinase binding site. Novel pyridine-based dihydrazones (3a-l) were synthesized by the condensation of appropriate aldehydes and pyridine-2,6-dicarbohydrazide (2) which was obtained by the treatment of dimethyl pyridine-2,6-dicarboxylate (1) with hydrazine hydrate. Structures of all the synthesized compounds were supported by their FTIR, 1H NMR, 13C NMR and microanalytical data. The compounds were screened primarily for their antibacterial activities as well as anticancer activities. None of the synthesized compounds had important antibacterial activity. Among the compounds which were tested against human colon cancer cell line (HT-29), compounds 3f and 3k showed significant activity (IC 50 =6.78 μM for compound 3f , IC 50 =8.88 μM for compound 3k). In addition, compound 3g exhibited promising activity against Ishikawa human endometrial cancer cell line (ISH) with an IC 50 value of 8.26 μM. At 10 μM, compounds 3f, 3k and 3g caused morphological changes of HT-29 and ISH cells and caspase-3 activation. In addition, these compounds were evaluated against NIH 3T3 mouse embriyonic fibroblast cell line and all synthesized compounds (3a-l) were found to be less toxic than paclitaxel. Moreover, possible inhibition mechanism of compound 3g was evaluated in silico against BRAF kinase enzyme. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00222860
Volume :
1223
Database :
Academic Search Index
Journal :
Journal of Molecular Structure
Publication Type :
Academic Journal
Accession number :
146872727
Full Text :
https://doi.org/10.1016/j.molstruc.2020.128962