Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: active inducers of testicular germ cell apoptosis
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.13/2474 |
Resumo: | Understanding of apoptosis or programmed cell death has provided the basis for novel therapeutics that has resulted in rationally designed anticancer strategies. Recently, inducers of apoptosis have been used in cancer therapy. In this work, we describe the role of chiral phthalimides functionalized with piperazines as potential apoptotic inducers. The listed twenty phthalimides were assessed for their in vitro apoptotic activity against testicular germ cells. All phthalimides showed a significant apoptotic response (∼39 to ∼68%). TUNEL assay and acridine orange fluorescence staining were carried out to investigate the molecular mechanisms responsible for the cell death. Phthalimides exhibited substantial apoptotic induction following the intrinsic pathway mechanism. Studies advocated that the apoptotic induction was mediated through caspase-9, caspase-3, JNK MAP kinase and tumor suppressor p53, which was accompanied by DNA fragmentation and nuclear condensation. Besides, the best five phthalimides regarding apoptotic action were evaluated for in vitro cytotoxic effects against CAL-72 and MCF-7 cancer cell lines. Compounds showed efficient killing of cancer cells. This discovery of functionalized phthalimides as apoptotic inducers would be highly valuable in understanding the mechanism of apoptosis at the molecular level and opens up new possibilities for therapeutic strategies. |
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Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: active inducers of testicular germ cell apoptosisPhthalimidesApoptosisMolecular dockingAryl piperazineCancer cells.Faculdade de Ciências Exatas e da EngenhariaCentro de Química da MadeiraUnderstanding of apoptosis or programmed cell death has provided the basis for novel therapeutics that has resulted in rationally designed anticancer strategies. Recently, inducers of apoptosis have been used in cancer therapy. In this work, we describe the role of chiral phthalimides functionalized with piperazines as potential apoptotic inducers. The listed twenty phthalimides were assessed for their in vitro apoptotic activity against testicular germ cells. All phthalimides showed a significant apoptotic response (∼39 to ∼68%). TUNEL assay and acridine orange fluorescence staining were carried out to investigate the molecular mechanisms responsible for the cell death. Phthalimides exhibited substantial apoptotic induction following the intrinsic pathway mechanism. Studies advocated that the apoptotic induction was mediated through caspase-9, caspase-3, JNK MAP kinase and tumor suppressor p53, which was accompanied by DNA fragmentation and nuclear condensation. Besides, the best five phthalimides regarding apoptotic action were evaluated for in vitro cytotoxic effects against CAL-72 and MCF-7 cancer cell lines. Compounds showed efficient killing of cancer cells. This discovery of functionalized phthalimides as apoptotic inducers would be highly valuable in understanding the mechanism of apoptosis at the molecular level and opens up new possibilities for therapeutic strategies.Indian Academy of SciencesDigitUMaSingh, Anil K.Bhardwaj, Jitender K.Olival, AnaKumar, YogeshPodder, AvijitMaheshwari, AnkurAgrawal, RenukaLatha, N.Singh, Brajendra K.Tomás, HelenaRodrigues, JoãoKishan, RamRupini, B.Rathi, Brijesh2019-07-10T11:16:30Z20162016-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.13/2474engSingh, A. K., Bhardwaj, J. K., Olival, A., Kumar, Y., Podder, A., Maheshwari, A., ... & Rodrigues, J. (2016). Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: active inducers of testicular germ cell apoptosis. Journal of Chemical Sciences, 128(8), 1245-1263.0974-362610.1007/s12039-016-1122-0info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-17T05:57:02Zoai:digituma.uma.pt:10400.13/2474Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:05:15.687500Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: active inducers of testicular germ cell apoptosis |
title |
Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: active inducers of testicular germ cell apoptosis |
spellingShingle |
Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: active inducers of testicular germ cell apoptosis Singh, Anil K. Phthalimides Apoptosis Molecular docking Aryl piperazine Cancer cells . Faculdade de Ciências Exatas e da Engenharia Centro de Química da Madeira |
title_short |
Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: active inducers of testicular germ cell apoptosis |
title_full |
Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: active inducers of testicular germ cell apoptosis |
title_fullStr |
Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: active inducers of testicular germ cell apoptosis |
title_full_unstemmed |
Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: active inducers of testicular germ cell apoptosis |
title_sort |
Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: active inducers of testicular germ cell apoptosis |
author |
Singh, Anil K. |
author_facet |
Singh, Anil K. Bhardwaj, Jitender K. Olival, Ana Kumar, Yogesh Podder, Avijit Maheshwari, Ankur Agrawal, Renuka Latha, N. Singh, Brajendra K. Tomás, Helena Rodrigues, João Kishan, Ram Rupini, B. Rathi, Brijesh |
author_role |
author |
author2 |
Bhardwaj, Jitender K. Olival, Ana Kumar, Yogesh Podder, Avijit Maheshwari, Ankur Agrawal, Renuka Latha, N. Singh, Brajendra K. Tomás, Helena Rodrigues, João Kishan, Ram Rupini, B. Rathi, Brijesh |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
DigitUMa |
dc.contributor.author.fl_str_mv |
Singh, Anil K. Bhardwaj, Jitender K. Olival, Ana Kumar, Yogesh Podder, Avijit Maheshwari, Ankur Agrawal, Renuka Latha, N. Singh, Brajendra K. Tomás, Helena Rodrigues, João Kishan, Ram Rupini, B. Rathi, Brijesh |
dc.subject.por.fl_str_mv |
Phthalimides Apoptosis Molecular docking Aryl piperazine Cancer cells . Faculdade de Ciências Exatas e da Engenharia Centro de Química da Madeira |
topic |
Phthalimides Apoptosis Molecular docking Aryl piperazine Cancer cells . Faculdade de Ciências Exatas e da Engenharia Centro de Química da Madeira |
description |
Understanding of apoptosis or programmed cell death has provided the basis for novel therapeutics that has resulted in rationally designed anticancer strategies. Recently, inducers of apoptosis have been used in cancer therapy. In this work, we describe the role of chiral phthalimides functionalized with piperazines as potential apoptotic inducers. The listed twenty phthalimides were assessed for their in vitro apoptotic activity against testicular germ cells. All phthalimides showed a significant apoptotic response (∼39 to ∼68%). TUNEL assay and acridine orange fluorescence staining were carried out to investigate the molecular mechanisms responsible for the cell death. Phthalimides exhibited substantial apoptotic induction following the intrinsic pathway mechanism. Studies advocated that the apoptotic induction was mediated through caspase-9, caspase-3, JNK MAP kinase and tumor suppressor p53, which was accompanied by DNA fragmentation and nuclear condensation. Besides, the best five phthalimides regarding apoptotic action were evaluated for in vitro cytotoxic effects against CAL-72 and MCF-7 cancer cell lines. Compounds showed efficient killing of cancer cells. This discovery of functionalized phthalimides as apoptotic inducers would be highly valuable in understanding the mechanism of apoptosis at the molecular level and opens up new possibilities for therapeutic strategies. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016 2016-01-01T00:00:00Z 2019-07-10T11:16:30Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.13/2474 |
url |
http://hdl.handle.net/10400.13/2474 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Singh, A. K., Bhardwaj, J. K., Olival, A., Kumar, Y., Podder, A., Maheshwari, A., ... & Rodrigues, J. (2016). Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: active inducers of testicular germ cell apoptosis. Journal of Chemical Sciences, 128(8), 1245-1263. 0974-3626 10.1007/s12039-016-1122-0 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Indian Academy of Sciences |
publisher.none.fl_str_mv |
Indian Academy of Sciences |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799129923741286400 |