Unknown

Dataset Information

0

Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts.


ABSTRACT: A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes 3a-h and related quaternary ammonium salts 4a-h were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series 3 and 4 to be potent cytotoxins with submicromolar CC50 values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure-activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, 3a-h are cytotoxic towards a number of leukemic and colon cancer cells. 4b,c lowered the mitochondrial membrane potential in CEM cells, and 4d induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely 3c,d and 4c-e, were identified as lead molecules that have drug-like properties.

SUBMITTER: Roayapalley PK 

PROVIDER: S-EPMC8659243 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts.

Roayapalley Praveen K PK   Dimmock Jonathan R JR   Contreras Lisett L   Balderrama Karol S KS   Aguilera Renato J RJ   Sakagami Hiroshi H   Amano Shigeru S   Sharma Rajendra K RK   Das Umashankar U  

Molecules (Basel, Switzerland) 20211125 23


A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes <b>3a</b>-<b>h</b> and related quaternary ammonium salts <b>4a</b>-<b>h</b> were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series <b>3</b> and <b>4</b> to be potent cytotoxins with submicromolar CC<sub>50</sub> values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HP  ...[more]

Similar Datasets

| S-EPMC9038131 | biostudies-literature
| S-EPMC10870019 | biostudies-literature
| S-EPMC8596621 | biostudies-literature
| S-EPMC6010013 | biostudies-literature
| S-EPMC4647383 | biostudies-literature
| S-EPMC8116641 | biostudies-literature
| S-EPMC5448849 | biostudies-other
| S-EPMC10685092 | biostudies-literature
| S-EPMC8539267 | biostudies-literature
| S-EPMC8938946 | biostudies-literature