A study on MAPK/ERK and CDK2-Cyclin-E signal switch "on and off" in cell proliferation by bis urea derivatives of 1, 4-Diisocyanatobenzene
Copyright © 2021 Elsevier Inc. All rights reserved..
A series of novel substituted bisurea 1,4-Diisocyanatobenzene compounds were designed, synthesized and introduced as potent anticancer compounds and screened for their in vitro anti-proliferative activities in human cancer cell lines. The structures of all titled compounds were characterized using Fourier-transform infrared mass spectra, nuclear magnetic resonance spectroscopy, elemental analysis and evaluated their sustainability using biological experiments. A selected group of ten derivatives were apprised for their anti-proliferative activity. The compounds 3d and 3e displayed potent anticancer activity with low IC50 value of 5.40, and 5.89 μM against HeLa cancer cell lines. The observed apoptosis data has demonstrated that compounds 3d and 3e induce the activaties of caspase-9 and caspase-3, the compounds 3d and 3e regulated fungal zone inhibition. Due to promising growth inhibitions, the all synthesized compounds were allowed to campaign includes quantum-polarized-ligand, quantum mechanical and molecular mechanical, docking experiments. The compounds 3d and 3e have exhibited a higher affinity for ERK/MAP kinase and CDK2 proteins. The molecular docking interactions have demonstrated two stage inhibition of cancer cells by binding with ERK/MAP kinase and CDK2 leads to inactivation of cell proliferation,cell cycle progression,cell divisionanddifferentiation, and hypo-phosphorylation of ribosome leading cells to restricts at point boundary of the G1/S phase. The long-range molecular dynamics, 150 ns, simulations were also revealed more consistency by 3d. Our study conclude good binding propensity for active-tunnel of ERK/MAP kinase and CDK2 proteins, by 3d (1,1'-(1,4-phenylene) bis(3-(2-chlorobenzyl)urea)), to suggest that the designed and synthesized 3d is to use as selective novel nuclei in anti-cancer chemotherapeutics.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:112 |
|---|---|
| Enthalten in: |
Bioorganic chemistry - 112(2021) vom: 06. Juli, Seite 104940 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Nagalakshmamma, Vadabingi [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 21.10.2021 Date Revised 21.10.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bioorg.2021.104940 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM325174512 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM325174512 | ||
| 003 | DE-627 | ||
| 005 | 20231225191857.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bioorg.2021.104940 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1083.xml |
| 035 | |a (DE-627)NLM325174512 | ||
| 035 | |a (NLM)33965780 | ||
| 035 | |a (PII)S0045-2068(21)00317-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Nagalakshmamma, Vadabingi |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A study on MAPK/ERK and CDK2-Cyclin-E signal switch "on and off" in cell proliferation by bis urea derivatives of 1, 4-Diisocyanatobenzene |
| 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 21.10.2021 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier Inc. All rights reserved. | ||
| 520 | |a A series of novel substituted bisurea 1,4-Diisocyanatobenzene compounds were designed, synthesized and introduced as potent anticancer compounds and screened for their in vitro anti-proliferative activities in human cancer cell lines. The structures of all titled compounds were characterized using Fourier-transform infrared mass spectra, nuclear magnetic resonance spectroscopy, elemental analysis and evaluated their sustainability using biological experiments. A selected group of ten derivatives were apprised for their anti-proliferative activity. The compounds 3d and 3e displayed potent anticancer activity with low IC50 value of 5.40, and 5.89 μM against HeLa cancer cell lines. The observed apoptosis data has demonstrated that compounds 3d and 3e induce the activaties of caspase-9 and caspase-3, the compounds 3d and 3e regulated fungal zone inhibition. Due to promising growth inhibitions, the all synthesized compounds were allowed to campaign includes quantum-polarized-ligand, quantum mechanical and molecular mechanical, docking experiments. The compounds 3d and 3e have exhibited a higher affinity for ERK/MAP kinase and CDK2 proteins. The molecular docking interactions have demonstrated two stage inhibition of cancer cells by binding with ERK/MAP kinase and CDK2 leads to inactivation of cell proliferation,cell cycle progression,cell divisionanddifferentiation, and hypo-phosphorylation of ribosome leading cells to restricts at point boundary of the G1/S phase. The long-range molecular dynamics, 150 ns, simulations were also revealed more consistency by 3d. Our study conclude good binding propensity for active-tunnel of ERK/MAP kinase and CDK2 proteins, by 3d (1,1'-(1,4-phenylene) bis(3-(2-chlorobenzyl)urea)), to suggest that the designed and synthesized 3d is to use as selective novel nuclei in anti-cancer chemotherapeutics | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a CDK2 | |
| 650 | 4 | |a Cancer | |
| 650 | 4 | |a Docking | |
| 650 | 4 | |a Dynamic simulation | |
| 650 | 4 | |a HeLa cell lines | |
| 650 | 4 | |a MAPK/ERK | |
| 650 | 7 | |a Antifungal Agents |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Benzene Derivatives |2 NLM | |
| 650 | 7 | |a CCNE1 protein, human |2 NLM | |
| 650 | 7 | |a Cyclin E |2 NLM | |
| 650 | 7 | |a Isocyanates |2 NLM | |
| 650 | 7 | |a Oncogene Proteins |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a Urea |2 NLM | |
| 650 | 7 | |a 8W8T17847W |2 NLM | |
| 650 | 7 | |a CDK2 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 650 | 7 | |a Cyclin-Dependent Kinase 2 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 700 | 1 | |a Venkataswamy, Mallepogu |e verfasserin |4 aut | |
| 700 | 1 | |a Pasala, Chiranjeevi |e verfasserin |4 aut | |
| 700 | 1 | |a Uma Maheswari, Amineni |e verfasserin |4 aut | |
| 700 | 1 | |a Thyaga Raju, Kedam |e verfasserin |4 aut | |
| 700 | 1 | |a Nagaraju, Chamarthi |e verfasserin |4 aut | |
| 700 | 1 | |a Chalapathi, Ponne V |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Bioorganic chemistry |d 1986 |g 112(2021) vom: 06. Juli, Seite 104940 |w (DE-627)NLM012846570 |x 1090-2120 |7 nnns |
| 773 | 1 | 8 | |g volume:112 |g year:2021 |g day:06 |g month:07 |g pages:104940 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bioorg.2021.104940 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 112 |j 2021 |b 06 |c 07 |h 104940 | ||