Novel Natural Inhibitors for Glioblastoma by Targeting Epidermal Growth Factor Receptor and Phosphoinositide 3-kinase
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
BACKGROUND/AIM: Glioblastoma is an extensively malignant neoplasm of the brain that predominantly impacts the human population. To address the challenge of glioblastoma, herein, we have searched for new drug-like candidates by extensive computational and biochemical investigations.
METHOD: Approximately 950 compounds were virtually screened against the two most promising targets of glioblastoma, i.e., epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K). Based on highly negative docking scores, excellent binding capabilities and good pharmacokinetic properties, eight and seven compounds were selected for EGFR and PI3K, respectively.
RESULTS: Among those hits, four natural products (SBEH-40, QUER, QTME-12, and HCFR) exerted dual inhibitory effects on EGFR and PI3K in our in-silico analysis; therefore, their capacity to suppress the cell proliferation was assessed in U87 cell line (type of glioma cell line). The compounds SBEH-40, QUER, andQTME-12 exhibited significant anti-proliferative capability with IC50 values of 11.97 ± 0.73 μM, 28.27 ± 1.52 μM, and 22.93 ± 1.63 μM respectively, while HCFR displayed weak inhibitory potency (IC50 = 74.97 ± 2.30 μM).
CONCLUSION: This study has identified novel natural products that inhibit the progression of glioblastoma; however, further examinations of these molecules are required in animal and tissue models to better understand their downstream targeting mechanisms.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
Current medicinal chemistry - (2024) vom: 09. Apr. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ullah, Atta [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
EGFR |
|---|
| Anmerkungen: |
Date Revised 15.04.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.2174/0109298673293279240404080046 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM371060842 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM371060842 | ||
| 003 | DE-627 | ||
| 005 | 20240415234527.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240415s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.2174/0109298673293279240404080046 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1376.xml |
| 035 | |a (DE-627)NLM371060842 | ||
| 035 | |a (NLM)38616761 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ullah, Atta |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Novel Natural Inhibitors for Glioblastoma by Targeting Epidermal Growth Factor Receptor and Phosphoinositide 3-kinase |
| 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 Revised 15.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND/AIM: Glioblastoma is an extensively malignant neoplasm of the brain that predominantly impacts the human population. To address the challenge of glioblastoma, herein, we have searched for new drug-like candidates by extensive computational and biochemical investigations | ||
| 520 | |a METHOD: Approximately 950 compounds were virtually screened against the two most promising targets of glioblastoma, i.e., epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K). Based on highly negative docking scores, excellent binding capabilities and good pharmacokinetic properties, eight and seven compounds were selected for EGFR and PI3K, respectively | ||
| 520 | |a RESULTS: Among those hits, four natural products (SBEH-40, QUER, QTME-12, and HCFR) exerted dual inhibitory effects on EGFR and PI3K in our in-silico analysis; therefore, their capacity to suppress the cell proliferation was assessed in U87 cell line (type of glioma cell line). The compounds SBEH-40, QUER, andQTME-12 exhibited significant anti-proliferative capability with IC50 values of 11.97 ± 0.73 μM, 28.27 ± 1.52 μM, and 22.93 ± 1.63 μM respectively, while HCFR displayed weak inhibitory potency (IC50 = 74.97 ± 2.30 μM) | ||
| 520 | |a CONCLUSION: This study has identified novel natural products that inhibit the progression of glioblastoma; however, further examinations of these molecules are required in animal and tissue models to better understand their downstream targeting mechanisms | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a EGFR | |
| 650 | 4 | |a Glioblastoma | |
| 650 | 4 | |a MTT assay | |
| 650 | 4 | |a PI3K | |
| 650 | 4 | |a U87 cell line. | |
| 650 | 4 | |a molecular docking | |
| 650 | 4 | |a virtual screening | |
| 700 | 1 | |a Ullah, Saeed |e verfasserin |4 aut | |
| 700 | 1 | |a Waqas, Muhammad |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Majid |e verfasserin |4 aut | |
| 700 | 1 | |a Rehman, Najeeb Ur |e verfasserin |4 aut | |
| 700 | 1 | |a Khalid, Asaad |e verfasserin |4 aut | |
| 700 | 1 | |a Jan, Afnan |e verfasserin |4 aut | |
| 700 | 1 | |a Aziz, Shahkar |e verfasserin |4 aut | |
| 700 | 1 | |a Naeem, Muhammad |e verfasserin |4 aut | |
| 700 | 1 | |a Halim, Sobia |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Ajmal |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Harrasi, Ahmed |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Current medicinal chemistry |d 1997 |g (2024) vom: 09. Apr. |w (DE-627)NLM093833857 |x 1875-533X |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:09 |g month:04 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.2174/0109298673293279240404080046 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 09 |c 04 | ||