An official website of the United States government

Cytotoxicity against human MCF7 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay

PubChem AID
2033979
Cell Line Target
MCF7
Primary Citation
Discovery of PIM-1 kinase inhibitors based on the 2,5-disubstituted 1,3,4-oxadiazole scaffold against prostate cancer: Design, synthesis, in vitro and in vivo cytotoxicity investigation [PMID: 36848846]
Source
External ID
BioAssay Type
Confirmatory
Tested Substances
Tested Compounds
Version
1.1
Status
Live
Dates
  • Deposit:
    2025-01-02
  • Modify:
    2025-01-02
Description
This bioassay record (AID 2033979) reports results from the above primary citation. Additional data from the same publication are reported in a total of 41 BioAssay records in PubChem.

1 Description

Title: Discovery of PIM-1 kinase inhibitors based on the 2,5-disubstituted 1,3,4-oxadiazole scaffold against prostate cancer: Design, synthesis, in vitro and in vivo cytotoxicity investigation.

Abstract: PIM-1 kinases play an established role in prostate cancer development and progression. This research work tackles the design and synthesis of new PIM-1 kinase targeting 2,5-disubstituted-1,3,4-oxadiazoles 10a-g&11a-f, and investigation thereof as potential anti-cancer agents through in vitro cytotoxicity assay followed by in vivo studies along with exploration of this chemotype's plausible mechanism of action. In vitro cytotoxicity experiments have disclosed 10f as the most potent derivative against PC-3 cells (IC50 = 16 nM) compared to the reference drug Staurosporine (IC50 = 0.36 μM), also eliciting good cytotoxicity against HepG2 and MCF-7 cells (IC50 = 0.13 and 5.37 μM, respectively). Investigating PIM-1 kinase inhibitory activity of compound 10f revealed an IC50 of 17 nM paralleled to that of Staurosporine (IC50 = 16.7 nM). Furthermore, compound 10f displayed an antioxidant activity eliciting a DPPH inhibition ratio of 94% as compared to Trolox (96%). Further investigation demonstrated that 10f induced apoptosis in treated PC-3 cells by 43.2-fold (19.44%) compared to 0.45% in control. 10f also disrupted the PC-3 cell cycle by increasing the cell population at the PreG1-phase by 19.29-fold while decreasing the G2/M-phase by 0.56-fold compared to control. Moreover, 10f affected a downregulation of JAK2, STAT3 and Bcl-2 and upregulation of caspases 3, 8 and 9 levels that activated the caspase-dependent apoptosis. Finally, in vivo 10f-treatment caused a significant increase in tumor inhibition by 64.2% compared to 44.5% in Staurosporine treatment of the PC-3 xenograft mouse model. Additionally, it improved the hematological, biochemical parameters, and histopathological examinations compared to control untreated animals. Finally, docking of 10f with the ATP-binding site of PIM-1 kinase demonstrated good recognition of and effective binding to the active site. In conclusion, compound 10f represents a promising lead compound that merits further future optimization for controlling prostate cancer.

2 Comment

Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Journal: Eur J Med Chem

Year: 2023

Volume: 250

First Page: 115220

Last Page: 115220

DOI: 10.1016/j.ejmech.2023.115220

Target ChEMBL ID: CHEMBL387

ChEMBL Target Name: MCF7

ChEMBL Target Type: CELL-LINE - Target is a specific cell-line

Relationship Type: N - Non-molecular target assigned

Confidence: Target assigned is non-molecular

3 Result Definitions

4 Data Table

5 Target

Cell Line Target
MCF7

7 Identity

7.1 BioAssay Name

Cytotoxicity against human MCF7 cells assessed as inhibition of cell growth incubated for 48 hrs by MTT assay

7.2 Source

7.3 External ID

7.4 Project Category

Literature, Extracted

7.5 BioAssay Type

Confirmatory

7.6 Deposit Date

2025-01-02

7.7 Modify Date

Version 1.1
2025-01-02 (currently shown)

7.8 Status

Live

8 Same-Publication BioAssays

9 Information Sources

  1. PubChem
  2. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
CONTENTS