Hybrids of 1,4-Quinone with Quinoline Derivatives : Synthesis, Biological Activity, and Molecular Docking with DT-Diaphorase (NQO1)
Hybrids 1,4-quinone with quinoline were obtained by connecting two active structures through an oxygen atom. This strategy allows to obtain new compounds with a high biological activity and suitable bioavailability. Newly synthesized compounds were characterized by various spectroscopic methods. The enzymatic assay used showed that these compounds were a suitable DT-diaphorase (NQO1) substrates as evidenced by increasing enzymatic conversion rates relative to that of streptonigrin. Hybrids were tested in vitro against a panel of human cell lines including melanoma, breast, and lung cancers. They showed also a high cytotoxic activity depending on the type of 1,4-quinone moiety and the applied tumor cell lines. It was found that cytotoxic activity of the studied hybrids was increasing against the cell lines with higher NQO1 protein level, such as breast (MCF-7 and T47D) and lung (A549) cancers. Selected hybrids were tested for the transcriptional activity of the gene encoding a proliferation marker (H3 histone), cell cycle regulators (p53 and p21) and the apoptosis pathway (BCL-2 and BAX). The molecular docking was used to examine the probable interaction between the hybrids and NQO1 protein.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
|---|---|
| Enthalten in: |
Molecules (Basel, Switzerland) - 27(2022), 19 vom: 21. Sept. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kadela-Tomanek, Monika [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 17.10.2022 Date Revised 19.10.2022 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/molecules27196206 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM347498078 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM347498078 | ||
| 003 | DE-627 | ||
| 005 | 20231226033952.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/molecules27196206 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1158.xml |
| 035 | |a (DE-627)NLM347498078 | ||
| 035 | |a (NLM)36234741 | ||
| 035 | |a (PII)6206 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kadela-Tomanek, Monika |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hybrids of 1,4-Quinone with Quinoline Derivatives |b Synthesis, Biological Activity, and Molecular Docking with DT-Diaphorase (NQO1) |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 17.10.2022 | ||
| 500 | |a Date Revised 19.10.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Hybrids 1,4-quinone with quinoline were obtained by connecting two active structures through an oxygen atom. This strategy allows to obtain new compounds with a high biological activity and suitable bioavailability. Newly synthesized compounds were characterized by various spectroscopic methods. The enzymatic assay used showed that these compounds were a suitable DT-diaphorase (NQO1) substrates as evidenced by increasing enzymatic conversion rates relative to that of streptonigrin. Hybrids were tested in vitro against a panel of human cell lines including melanoma, breast, and lung cancers. They showed also a high cytotoxic activity depending on the type of 1,4-quinone moiety and the applied tumor cell lines. It was found that cytotoxic activity of the studied hybrids was increasing against the cell lines with higher NQO1 protein level, such as breast (MCF-7 and T47D) and lung (A549) cancers. Selected hybrids were tested for the transcriptional activity of the gene encoding a proliferation marker (H3 histone), cell cycle regulators (p53 and p21) and the apoptosis pathway (BCL-2 and BAX). The molecular docking was used to examine the probable interaction between the hybrids and NQO1 protein | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 1,4-quinone | |
| 650 | 4 | |a anticancer activity | |
| 650 | 4 | |a molecular docking | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Benzoquinones |2 NLM | |
| 650 | 7 | |a Histones |2 NLM | |
| 650 | 7 | |a Hydroxyquinolines |2 NLM | |
| 650 | 7 | |a Quinolines |2 NLM | |
| 650 | 7 | |a Quinones |2 NLM | |
| 650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
| 650 | 7 | |a bcl-2-Associated X Protein |2 NLM | |
| 650 | 7 | |a Streptonigrin |2 NLM | |
| 650 | 7 | |a 261Q3JB310 |2 NLM | |
| 650 | 7 | |a quinone |2 NLM | |
| 650 | 7 | |a 3T006GV98U |2 NLM | |
| 650 | 7 | |a NAD(P)H Dehydrogenase (Quinone) |2 NLM | |
| 650 | 7 | |a EC 1.6.5.2 |2 NLM | |
| 650 | 7 | |a NQO1 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.6.5.2 |2 NLM | |
| 650 | 7 | |a Oxygen |2 NLM | |
| 650 | 7 | |a S88TT14065 |2 NLM | |
| 700 | 1 | |a Jastrzębska, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Chrobak, Elwira |e verfasserin |4 aut | |
| 700 | 1 | |a Bębenek, Ewa |e verfasserin |4 aut | |
| 700 | 1 | |a Latocha, Małgorzata |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecules (Basel, Switzerland) |d 2004 |g 27(2022), 19 vom: 21. Sept. |w (DE-627)NLM172073448 |x 1420-3049 |7 nnns |
| 773 | 1 | 8 | |g volume:27 |g year:2022 |g number:19 |g day:21 |g month:09 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/molecules27196206 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 27 |j 2022 |e 19 |b 21 |c 09 | ||