Targeting AKT2 in MDA-MB-231 Cells by Pyrazole Hybrids: Structural, Biological and Molecular Docking Studies.
ADME
chalcone
cytotoxic
docking
pyrazole
Journal
Chemistry & biodiversity
ISSN: 1612-1880
Titre abrégé: Chem Biodivers
Pays: Switzerland
ID NLM: 101197449
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
01
06
2023
accepted:
11
09
2023
medline:
29
11
2023
pubmed:
13
9
2023
entrez:
13
9
2023
Statut:
ppublish
Résumé
Pyrazolic hybrids appended with naphthalene, p-chlorobenzene, o-phenol and toluene have been synthesized using Claisen Schmidt condensation reaction of 1-benzyl-3,5-dimethyl-1H-pyrazole-4-carbaldehyde. All compounds were characterized by various spectroscopic techniques. Compound (E)-3-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)-1-(4-chlorophenyl)prop-2-en-1-one crystallizes in monoclinic crystal system with C2/c space group. These synthesized compounds were tested for cytotoxic activity and among these compounds 4b and 5a shows prominent cytotoxic activity against triple-negative breast cancer (TNBC) cells MDA-MB-231 with IC50 values 47.72 μM and 24.25 μM, respectively. Distinguishing morphological changes were noticed in MDA-MB-231 cells treated with pyrazole hybrids contributing to apoptosis action. To get more insight into cytotoxic activity, in silico molecular docking of these compounds were performed and the results suggested that (E)-3-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)-1-(p-tolyl)prop-2-en-1-one and 1-(1'-benzyl-5-(4-chlorophenyl)-3',5'-dimethyl-3,4-dihydro-1'H,2H-[3,4'-bipyrazol]-2-yl)ethan-1-one binds to the prominent domain of Akt2 indicating their potential ability as Akt2 inhibitor. Moreover, from in silico ADME studies clearly demonstrated that these compounds may be regarded as a drug candidate for sub-lingual absorption based on log p values (2.157-4.924). These compounds also show promising antitubercular activity. The overall results suggest that pyrazolic hybrids with substitution at less sterically hindered positions have appealing potent cytotoxic activity and antituberculosis activity due to which they may act as multidrug candidate.
Identifiants
pubmed: 37702285
doi: 10.1002/cbdv.202300799
doi:
Substances chimiques
Antineoplastic Agents
0
Pyrazoles
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202300799Subventions
Organisme : Principal, R. B. Narayanrao Borawake College, Shrirampur and Research Center, Shri Chhatrapati Shivaji Mahavidyalaya, Shrigonda
Organisme : UGC, New Delhi, India
ID : 47-1124-14
Organisme : UGC, New Delhi, India
ID : ST-56/WRO
Informations de copyright
© 2023 Wiley-VHCA AG, Zurich, Switzerland.
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