Design, synthesis and biological activity of 1,4-quinone moiety attached to betulin derivatives as potent DT-diaphorase substrate
Copyright © 2020 Elsevier Inc. All rights reserved..
In this research, betulin derivatives were bonded to the 1,4-quinone fragment by triazole linker. Furthermore, the enzymatic assay used has shown that these compounds are a good DT-diaphorase (NQO1) substrates as evidenced by increasing enzymatic conversion rates relative to that of streptonigrin. The anticancer activities of the hybrids were tested against a panel of human cell lines, like: melanoma, ovarian, breast, colon, and lung cancers. The structure-activity relationship showed that the activity depends on the type of 1,4-quinone moiety and the tumor cell lines used. It was also found that the anticancer effects were increasing against the cell line with higher NQO1 protein level, like: breast (T47D, MCF-7), colon (Caco-2), and lung (A549) cancers. The transcriptional activity of the gene encoding a proliferation marker (H3 histone), cell cycle regulators (p53 and p21) and apoptosis pathway (BCL-2 and BAX) for selected compounds were determined. The molecular docking study was carried out to examine the interaction between the hybrids and NQO1 enzyme. The computational simulation showed that the type of the 1,4-quinone moiety influences location of the compound in the active site of the enzyme. It is worth noting that the study of new hybrids of betulin as substrate for NQO1 protein may lead to new medical therapeutic applications in the future.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:106 |
|---|---|
| Enthalten in: |
Bioorganic chemistry - 106(2021) vom: 08. Jan., Seite 104478 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kadela-Tomanek, Monika [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 08.09.2021 Date Revised 08.09.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bioorg.2020.104478 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM318387522 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM318387522 | ||
| 003 | DE-627 | ||
| 005 | 20231225165241.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bioorg.2020.104478 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1061.xml |
| 035 | |a (DE-627)NLM318387522 | ||
| 035 | |a (NLM)33272711 | ||
| 035 | |a (PII)S0045-2068(20)31776-4 | ||
| 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 Design, synthesis and biological activity of 1,4-quinone moiety attached to betulin derivatives as potent DT-diaphorase substrate |
| 264 | 1 | |c 2021 | |
| 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 08.09.2021 | ||
| 500 | |a Date Revised 08.09.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a In this research, betulin derivatives were bonded to the 1,4-quinone fragment by triazole linker. Furthermore, the enzymatic assay used has shown that these compounds are a good DT-diaphorase (NQO1) substrates as evidenced by increasing enzymatic conversion rates relative to that of streptonigrin. The anticancer activities of the hybrids were tested against a panel of human cell lines, like: melanoma, ovarian, breast, colon, and lung cancers. The structure-activity relationship showed that the activity depends on the type of 1,4-quinone moiety and the tumor cell lines used. It was also found that the anticancer effects were increasing against the cell line with higher NQO1 protein level, like: breast (T47D, MCF-7), colon (Caco-2), and lung (A549) cancers. The transcriptional activity of the gene encoding a proliferation marker (H3 histone), cell cycle regulators (p53 and p21) and apoptosis pathway (BCL-2 and BAX) for selected compounds were determined. The molecular docking study was carried out to examine the interaction between the hybrids and NQO1 enzyme. The computational simulation showed that the type of the 1,4-quinone moiety influences location of the compound in the active site of the enzyme. It is worth noting that the study of new hybrids of betulin as substrate for NQO1 protein may lead to new medical therapeutic applications in the future | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 1,4-Naphthoquinone | |
| 650 | 4 | |a 5,8-Quinolinedione | |
| 650 | 4 | |a Anticancer activity | |
| 650 | 4 | |a Betulin | |
| 650 | 4 | |a Molecular docking study | |
| 650 | 4 | |a NQO1 protein | |
| 650 | 4 | |a Triazole | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Enzyme Inhibitors |2 NLM | |
| 650 | 7 | |a Quinones |2 NLM | |
| 650 | 7 | |a Triterpenes |2 NLM | |
| 650 | 7 | |a betulin |2 NLM | |
| 650 | 7 | |a 6W70HN7X7O |2 NLM | |
| 650 | 7 | |a NAD(P)H Dehydrogenase (Quinone) |2 NLM | |
| 650 | 7 | |a EC 1.6.5.2 |2 NLM | |
| 700 | 1 | |a Jastrzębska, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Marciniec, Krzysztof |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 | |
| 700 | 1 | |a Kuśmierz, Dariusz |e verfasserin |4 aut | |
| 700 | 1 | |a Boryczka, Stanisław |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Bioorganic chemistry |d 1986 |g 106(2021) vom: 08. Jan., Seite 104478 |w (DE-627)NLM012846570 |x 1090-2120 |7 nnns |
| 773 | 1 | 8 | |g volume:106 |g year:2021 |g day:08 |g month:01 |g pages:104478 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bioorg.2020.104478 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 106 |j 2021 |b 08 |c 01 |h 104478 | ||