Dichloroacetyl Amides of 3,5-Bis(benzylidene)-4-piperidones Displaying Greater Toxicity to Neoplasms than to Non-Malignant Cells.
Medicines (Basel)
; 9(6)2022 Jun 08.
Article
em En
| MEDLINE
| ID: mdl-35736248
ABSTRACT
A series of 3,5-bis(benzylidene)-1-dichloroacetyl-4-piperidones 1a-l was evaluated against Ca9-22, HSC-2, HSC-3, and HSC-4 squamous cell carcinomas. Virtually all of the compounds displayed potent cytotoxicity, with 83% of the CC50 values being submicromolar and several CC50 values being in the double digit nanomolar range. The compounds were appreciably less toxic to human HGF, HPLF, and HPC non-malignant cells, which led to some noteworthy selectivity index (SI) figures. From these studies, 1d,g,k emerged as the lead molecules in terms of their potencies and SI values. A Quantitative Structure-Activity Relationship (QSAR) study revealed that cytotoxic potencies and potency-selectivity expression figures increased when the magnitude of the sigma values in the aryl rings was elevated. The modes of action of the representative cytotoxins in Ca9-22 cells were found to include G2/M arrest and stimulation of the cells to undergo mitosis and cause poly(ADP-ribose) polymerase (PARP) and procaspase 3 cleavage.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Medicines (Basel)
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos