Synthesis and In Vitro Antitumor Activity of Novel Bivalent β-Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target
A series of novel bivalent β-carboline derivatives were designed and synthesized, and in vitro cytotoxicity, cell apoptosis, and DNA-binding affinity were evaluated. The cytotoxic results demonstrated that most bivalent β-carboline derivatives exhibited stronger cytotoxicity than the corresponding monomer against the five selected tumor cell lines (A549, SGC-7901, Hela, SMMC-7721, and MCF-7), indicating that the dimerization at the C³ position could enhance the antitumor activity of β-carbolines. Among the derivatives tested, 4B, 6i, 4D, and 6u displayed considerable cytotoxicity against A549 cell line. Furthermore, 4B, 6i, 4D, and 6u induced cell apoptosis in a dose-dependent manner, and caused cell cycle arrest at the S and G2/M phases. Moreover, the levels of cytochrome C in mitochondria, and the expressions of bcl-2 protein, decreased after treatment with β-carbolines, which indicated that 6i and 6u could induce mitochondria-mediated apoptosis. In addition, the results of UV-visible spectral, thermal denaturation, and molecular docking studies revealed that 4B, 6i, 4D, and 6u could bind to DNA mainly by intercalation.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
|---|---|
| Enthalten in: |
International journal of molecular sciences - 19(2018), 10 vom: 15. Okt. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gu, Hongling [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
74214-63-4 |
|---|
| Anmerkungen: |
Date Completed 14.01.2019 Date Revised 04.10.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/ijms19103179 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM289613922 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM289613922 | ||
| 003 | DE-627 | ||
| 005 | 20231225062938.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms19103179 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0965.xml |
| 035 | |a (DE-627)NLM289613922 | ||
| 035 | |a (NLM)30326662 | ||
| 035 | |a (PII)E3179 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gu, Hongling |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Synthesis and In Vitro Antitumor Activity of Novel Bivalent β-Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target |
| 264 | 1 | |c 2018 | |
| 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 14.01.2019 | ||
| 500 | |a Date Revised 04.10.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a A series of novel bivalent β-carboline derivatives were designed and synthesized, and in vitro cytotoxicity, cell apoptosis, and DNA-binding affinity were evaluated. The cytotoxic results demonstrated that most bivalent β-carboline derivatives exhibited stronger cytotoxicity than the corresponding monomer against the five selected tumor cell lines (A549, SGC-7901, Hela, SMMC-7721, and MCF-7), indicating that the dimerization at the C³ position could enhance the antitumor activity of β-carbolines. Among the derivatives tested, 4B, 6i, 4D, and 6u displayed considerable cytotoxicity against A549 cell line. Furthermore, 4B, 6i, 4D, and 6u induced cell apoptosis in a dose-dependent manner, and caused cell cycle arrest at the S and G2/M phases. Moreover, the levels of cytochrome C in mitochondria, and the expressions of bcl-2 protein, decreased after treatment with β-carbolines, which indicated that 6i and 6u could induce mitochondria-mediated apoptosis. In addition, the results of UV-visible spectral, thermal denaturation, and molecular docking studies revealed that 4B, 6i, 4D, and 6u could bind to DNA mainly by intercalation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DNA-binding affinity | |
| 650 | 4 | |a antitumor | |
| 650 | 4 | |a apoptosis | |
| 650 | 4 | |a bcl-2 | |
| 650 | 4 | |a bivalent β-carbolines | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Apoptosis Regulatory Proteins |2 NLM | |
| 650 | 7 | |a Carbolines |2 NLM | |
| 650 | 7 | |a carboline-3-carboxylic acid |2 NLM | |
| 650 | 7 | |a 74214-63-4 |2 NLM | |
| 700 | 1 | |a Li, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Jiangkun |e verfasserin |4 aut | |
| 700 | 1 | |a Xi, Yaxi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Shijun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Junru |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 19(2018), 10 vom: 15. Okt. |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
| 773 | 1 | 8 | |g volume:19 |g year:2018 |g number:10 |g day:15 |g month:10 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms19103179 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 19 |j 2018 |e 10 |b 15 |c 10 | ||