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Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring

A series of 3,5-bis(benzylidene)-4-piperidones 2a–u were prepared as candidate cytotoxic agents. In general, the compounds are highly toxic to human gingival carcinoma (Ca9-22), human squamous carcinoma-2 (HSC-2) and human squamous carcinoma-4 (HSC-4) neoplasms, but less so towards non-malignant hum...

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Autores principales: Roayapalley, Praveen K., Sakagami, Hiroshi, Satoh, Keitaro, Amano, Shigeru, Bandow, Kenjiro, Aguilera, Renato J., Hernandez, Karla G. Cano, Schiaffino Bustamante, Austre Y., Dimmock, Stephen G., Sharma, Rajendra K., Das, Umashankar, Dimmock, Jonathan R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707244/
https://www.ncbi.nlm.nih.gov/pubmed/34940290
http://dx.doi.org/10.3390/medicines8120078
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author Roayapalley, Praveen K.
Sakagami, Hiroshi
Satoh, Keitaro
Amano, Shigeru
Bandow, Kenjiro
Aguilera, Renato J.
Hernandez, Karla G. Cano
Schiaffino Bustamante, Austre Y.
Dimmock, Stephen G.
Sharma, Rajendra K.
Das, Umashankar
Dimmock, Jonathan R.
author_facet Roayapalley, Praveen K.
Sakagami, Hiroshi
Satoh, Keitaro
Amano, Shigeru
Bandow, Kenjiro
Aguilera, Renato J.
Hernandez, Karla G. Cano
Schiaffino Bustamante, Austre Y.
Dimmock, Stephen G.
Sharma, Rajendra K.
Das, Umashankar
Dimmock, Jonathan R.
author_sort Roayapalley, Praveen K.
collection PubMed
description A series of 3,5-bis(benzylidene)-4-piperidones 2a–u were prepared as candidate cytotoxic agents. In general, the compounds are highly toxic to human gingival carcinoma (Ca9-22), human squamous carcinoma-2 (HSC-2) and human squamous carcinoma-4 (HSC-4) neoplasms, but less so towards non-malignant human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF) and human pulp cells (HPC), thereby demonstrating tumour-selective toxicity. A further study revealed that most of the compounds in series 2 were more toxic to the human Colo-205 adenocarcinoma cell line (Colo-205), human HT29 colorectal adenocarcinoma cells (HT-29) and human CEM lymphoid cells (CEM) neoplasms than towards non-malignant human foreskin Hs27 fibroblast line (Hs27) cells. The potency of the cytotoxins towards the six malignant cell lines increased as the sigma and sigma star values of the aryl substituents rose. Attempts to condense various aryl aldehydes with 2,2,6,6-tetramethyl-4-piperidone led to the isolation of some 1,5-diaryl-1,4-pentadien-3-ones. The highest specificity for oral cancer cells was displayed by 2e and 2r. In the case of 2r, its selective toxicity exceeded that of doxorubicin and melphalan. The enones 2k, m, o have the highest SI values towards colon cancer and leukemic cells. Both 2e,r inhibited mitosis and increased the subG1 population (with a transient increase in G2/M phase cells). Slight activation of caspase-3, based on the cleavage of poly(ADP-ribose)polymerase (PARP) and procaspase 3, was detected.
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spelling pubmed-87072442021-12-25 Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring Roayapalley, Praveen K. Sakagami, Hiroshi Satoh, Keitaro Amano, Shigeru Bandow, Kenjiro Aguilera, Renato J. Hernandez, Karla G. Cano Schiaffino Bustamante, Austre Y. Dimmock, Stephen G. Sharma, Rajendra K. Das, Umashankar Dimmock, Jonathan R. Medicines (Basel) Article A series of 3,5-bis(benzylidene)-4-piperidones 2a–u were prepared as candidate cytotoxic agents. In general, the compounds are highly toxic to human gingival carcinoma (Ca9-22), human squamous carcinoma-2 (HSC-2) and human squamous carcinoma-4 (HSC-4) neoplasms, but less so towards non-malignant human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF) and human pulp cells (HPC), thereby demonstrating tumour-selective toxicity. A further study revealed that most of the compounds in series 2 were more toxic to the human Colo-205 adenocarcinoma cell line (Colo-205), human HT29 colorectal adenocarcinoma cells (HT-29) and human CEM lymphoid cells (CEM) neoplasms than towards non-malignant human foreskin Hs27 fibroblast line (Hs27) cells. The potency of the cytotoxins towards the six malignant cell lines increased as the sigma and sigma star values of the aryl substituents rose. Attempts to condense various aryl aldehydes with 2,2,6,6-tetramethyl-4-piperidone led to the isolation of some 1,5-diaryl-1,4-pentadien-3-ones. The highest specificity for oral cancer cells was displayed by 2e and 2r. In the case of 2r, its selective toxicity exceeded that of doxorubicin and melphalan. The enones 2k, m, o have the highest SI values towards colon cancer and leukemic cells. Both 2e,r inhibited mitosis and increased the subG1 population (with a transient increase in G2/M phase cells). Slight activation of caspase-3, based on the cleavage of poly(ADP-ribose)polymerase (PARP) and procaspase 3, was detected. MDPI 2021-12-16 /pmc/articles/PMC8707244/ /pubmed/34940290 http://dx.doi.org/10.3390/medicines8120078 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Roayapalley, Praveen K.
Sakagami, Hiroshi
Satoh, Keitaro
Amano, Shigeru
Bandow, Kenjiro
Aguilera, Renato J.
Hernandez, Karla G. Cano
Schiaffino Bustamante, Austre Y.
Dimmock, Stephen G.
Sharma, Rajendra K.
Das, Umashankar
Dimmock, Jonathan R.
Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring
title Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring
title_full Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring
title_fullStr Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring
title_full_unstemmed Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring
title_short Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring
title_sort cytotoxic tumour-selective 1,5-diaryl-3-oxo-1,4-pentadienes mounted on a piperidine ring
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707244/
https://www.ncbi.nlm.nih.gov/pubmed/34940290
http://dx.doi.org/10.3390/medicines8120078
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