Back to Search
Start Over
Synthesis and Biological Evaluation of Pyrazoline and Pyrrolidine-2,5-dione Hybrids as Potential Antitumor Agents.
- Source :
-
ChemMedChem [ChemMedChem] 2020 Oct 05; Vol. 15 (19), pp. 1813-1825. Date of Electronic Publication: 2020 Sep 02. - Publication Year :
- 2020
-
Abstract
- In search of novel and effective antitumor agents, pyrazoline-substituted pyrrolidine-2,5-dione hybrids were designed, synthesized and evaluated in silico, in vitro and in vivo for anticancer efficacy. All the compounds exhibited remarkable cytotoxic effects in MCF7 and HT29 cells. The excellent antiproliferative activity toward MCF7 (IC <subscript>50</subscript> =0.78±0.01 μM), HT29 (IC <subscript>50</subscript> =0.92±0.15 μM) and K562 (IC <subscript>50</subscript> =47.25±1.24 μM) cell lines, prompted us to further investigate the antitumor effects of the best compound S2 (1-(2-(3-(4-fluorophenyl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethyl)pyrrolidine-2,5-dione). In cell-cycle analysis, S2 was found to disrupt the growth phases with increased cell population in G <subscript>1</subscript> /G <subscript>0</subscript> phase and decreased cell population in G <subscript>2</subscript> /M phase. The excellent in vitro effects were also supported by inhibition of anti-apoptotic protein Bcl-2. In vivo tumor regression studies of S2 in HT29 xenograft nude mice, exhibited equivalent and promising tumor regression with maximum TGI, 66 % (i. p. route) and 60 % (oral route) at 50 mg kg <superscript>-1</superscript> dose by both the routes, indicating oral bioavailability and antitumor efficacy. These findings advocate that hybridization of pyrazoline and pyrrolidine-2,5-dioes holds promise for the development of more potent and less toxic anticancer agents.<br /> (© 2020 Wiley-VCH GmbH.)
- Subjects :
- Animals
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Cell Line, Tumor
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Molecular Docking Simulation
Molecular Structure
Neoplasms, Experimental drug therapy
Neoplasms, Experimental metabolism
Neoplasms, Experimental pathology
Pyrazoles chemical synthesis
Pyrazoles chemistry
Pyrrolidines chemical synthesis
Pyrrolidines chemistry
Structure-Activity Relationship
Antineoplastic Agents pharmacology
Pyrazoles pharmacology
Pyrrolidines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1860-7187
- Volume :
- 15
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- ChemMedChem
- Publication Type :
- Academic Journal
- Accession number :
- 32715626
- Full Text :
- https://doi.org/10.1002/cmdc.202000458