| Title |
Synthesis and antiproliferative activity of 2,4,6,7-tetrasubstituted-2H-pyrazolo[4,3-c]pyridines / |
| Authors |
Razmienė, Beatričė ; Řezníčková, Eva ; Dambrauskienė, Vaida ; Ostruszka, Radek ; Kubala, Martin ; Žukauskaitė, Asta ; Kryštof, Vladimír ; Šačkus, Algirdas ; Arbačiauskienė, Eglė |
| DOI |
10.3390/molecules26216747 |
| Full Text |
|
| Is Part of |
Molecules.. Basel : MDPI. 2021, vol. 26, iss. 21, art. no. 6747, p. 1-28.. ISSN 1420-3049 |
| Keywords [eng] |
antiproliferation ; cell death ; cross-coupling ; cycloiodination ; pyrazole ; pyridine |
| Abstract [eng] |
A library of 2,4,6,7-tetrasubstituted-2H-pyrazolo[4,3-c]pyridines was prepared from easily accessible 1-phenyl-3-(2-phenylethynyl)-1H-pyrazole-4-carbaldehyde via an iodine-mediated electrophilic cyclization of intermediate 4-(azidomethyl)-1-phenyl-3-(phenylethynyl)-1H-pyrazoles to 7-iodo-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridines followed by Suzuki cross-couplings with various boronic acids and alkylation reactions. The compounds were evaluated for their antiproliferative activity against K562, MV4-11, and MCF-7 cancer cell lines. The most potent compounds displayed low micromolar GI50 values. 4-(2,6-Diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol proved to be the most active, induced poly(ADP-ribose) polymerase 1 (PARP-1) cleavage, activated the initiator enzyme of apoptotic cascade caspase 9, induced a fragmentation of microtubule-associated protein 1- light chain 3 (LC3), and reduced the expression levels of proliferating cell nuclear antigen (PCNA). The obtained results suggest a complex action of 4-(2,6-diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol that combines antiproliferative effects with the induction of cell death. Moreover, investigations of the fluorescence properties of the final compounds revealed 7-(4-methoxyphenyl)-2,6-diphenyl-2Hpyrazolo[ 4,3-c]pyridine as the most potent pH indicator that enables both fluorescence intensity-based and ratiometric pH sensing. |
| Published |
Basel : MDPI |
| Type |
Journal article |
| Language |
English |
| Publication date |
2021 |
| CC license |
|
