Cyclic Amines Coupled to Indole Derivatives With Improved Efflux Pump Inhibiting Activity in Bacteria and Cancer Cells
Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved..
BACKGROUND/AIM: Indole skeleton has become a significant tool in the field of anticancer and antibacterial therapeutic strategies. The modified aza-Friedel-Crafts reaction by direct coupling of different cyclic imines and indole derivatives has been explored. To investigate the scope and limitations of the reaction and observe the effect of structural modifications, our aim was to resynthesize selected compounds as well as prepare new derivatives starting from 6,7-dimethoxy-3,4-dihydroisoquinoline, (4aR,8aR)-4a,5,6,7,8,8a-hexahydroquinoxalin-2(1H)-one and 7-azaindole. Our further aim was the systematic biological evaluation of selected C-3-coupled indole and azaindole derivatives in favour of having a preliminary overview about the structure-activity relationships.
MATERIALS AND METHODS: The synthesis and resynthesis of selected compounds were accomplished by extension of aza-Friedel-Crafts reaction. The products have been tested on bacteria and cancer cells.
RESULTS: The most significant efflux pump inhibiting (EPI) activity was observed in the case of 6,7-dihydrothieno[3,2-c]pyridine coupled indole derivative. The reaction of 6,7-dimethoxy-3,4-dihydroisoquinoline with 7-azaindole resulted in the most potent biofilm inhibitor product. Applying indole and 4,9-dihydro-3H-β-carboline, 6,7-dihydrothieno[3,2-c]pyridine led to the formation of a product with the highest anticancer activity. 6,7-Dimethoxy-3,4-dihydroisoquinoline skeleton and indole as an electron-rich aromatic compound have been found to be effective in the inhibition of ABCB1.
CONCLUSION: The compounds presented in the study were investigated regarding different aspects of antibacterial and anticancer activities. Accordingly, some compounds were found to have antibacterial effect on Escherichia coli and Staphylococcus aureus strains, certain C-3-coupled derivatives showed toxicity on sensitive and ABCB1 efflux pump expressing colon adenocarcinoma and a normal, non-cancerous fibroblast cell lines.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:44 |
|---|---|
| Enthalten in: |
Anticancer research - 44(2024), 3 vom: 29. März, Seite 1149-1160 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hegedűs, Dóra [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 04.03.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.21873/anticanres.16910 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369135296 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369135296 | ||
| 003 | DE-627 | ||
| 005 | 20240304232724.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240301s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.21873/anticanres.16910 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1316.xml |
| 035 | |a (DE-627)NLM369135296 | ||
| 035 | |a (NLM)38423632 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hegedűs, Dóra |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cyclic Amines Coupled to Indole Derivatives With Improved Efflux Pump Inhibiting Activity in Bacteria and Cancer Cells |
| 264 | 1 | |c 2024 | |
| 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 04.03.2024 | ||
| 500 | |a Date Revised 04.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. | ||
| 520 | |a BACKGROUND/AIM: Indole skeleton has become a significant tool in the field of anticancer and antibacterial therapeutic strategies. The modified aza-Friedel-Crafts reaction by direct coupling of different cyclic imines and indole derivatives has been explored. To investigate the scope and limitations of the reaction and observe the effect of structural modifications, our aim was to resynthesize selected compounds as well as prepare new derivatives starting from 6,7-dimethoxy-3,4-dihydroisoquinoline, (4aR,8aR)-4a,5,6,7,8,8a-hexahydroquinoxalin-2(1H)-one and 7-azaindole. Our further aim was the systematic biological evaluation of selected C-3-coupled indole and azaindole derivatives in favour of having a preliminary overview about the structure-activity relationships | ||
| 520 | |a MATERIALS AND METHODS: The synthesis and resynthesis of selected compounds were accomplished by extension of aza-Friedel-Crafts reaction. The products have been tested on bacteria and cancer cells | ||
| 520 | |a RESULTS: The most significant efflux pump inhibiting (EPI) activity was observed in the case of 6,7-dihydrothieno[3,2-c]pyridine coupled indole derivative. The reaction of 6,7-dimethoxy-3,4-dihydroisoquinoline with 7-azaindole resulted in the most potent biofilm inhibitor product. Applying indole and 4,9-dihydro-3H-β-carboline, 6,7-dihydrothieno[3,2-c]pyridine led to the formation of a product with the highest anticancer activity. 6,7-Dimethoxy-3,4-dihydroisoquinoline skeleton and indole as an electron-rich aromatic compound have been found to be effective in the inhibition of ABCB1 | ||
| 520 | |a CONCLUSION: The compounds presented in the study were investigated regarding different aspects of antibacterial and anticancer activities. Accordingly, some compounds were found to have antibacterial effect on Escherichia coli and Staphylococcus aureus strains, certain C-3-coupled derivatives showed toxicity on sensitive and ABCB1 efflux pump expressing colon adenocarcinoma and a normal, non-cancerous fibroblast cell lines | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a P-glycoprotein (ABCB1) inhibition | |
| 650 | 4 | |a anti-biofilm | |
| 650 | 4 | |a aza-Friedel–Crafts reaction | |
| 650 | 4 | |a efflux pump inhibitor (EPI) | |
| 650 | 4 | |a indole skeleton | |
| 650 | 4 | |a modified Mannich reaction | |
| 650 | 7 | |a Antipsychotic Agents |2 NLM | |
| 650 | 7 | |a Adamantane |2 NLM | |
| 650 | 7 | |a PJY633525U |2 NLM | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Amines |2 NLM | |
| 700 | 1 | |a Szemerédi, Nikoletta |e verfasserin |4 aut | |
| 700 | 1 | |a Gábor, Maja |e verfasserin |4 aut | |
| 700 | 1 | |a Sas, Judit |e verfasserin |4 aut | |
| 700 | 1 | |a Belasri, Khadija |e verfasserin |4 aut | |
| 700 | 1 | |a Szatmári, István |e verfasserin |4 aut | |
| 700 | 1 | |a Spengler, Gabriella |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Anticancer research |d 1987 |g 44(2024), 3 vom: 29. März, Seite 1149-1160 |w (DE-627)NLM012601454 |x 1791-7530 |7 nnns |
| 773 | 1 | 8 | |g volume:44 |g year:2024 |g number:3 |g day:29 |g month:03 |g pages:1149-1160 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.21873/anticanres.16910 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 44 |j 2024 |e 3 |b 29 |c 03 |h 1149-1160 | ||