Cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitors

A potential microtubule destabilising series of new indolizine derivatives was synthesised and tested for their anticancer activity against a panel of 60 human cancer cell lines. Compounds 11a, 11b, 15a, and 15j showed a broad spectrum of growth inhibitory activity against cancer cell lines represen...

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Main Authors:	Monica-Cornelia Sardaru, Anda Mihaela Craciun, Cristina-Maria Al Matarneh, Isabela Andreea Sandu, Roxana Maria Amarandi, Lacramioara Popovici, Catalina Ionica Ciobanu, Dragos Peptanariu, Mariana Pinteala, Ionel I. Mangalagiu, Ramona Danac
Format:	Article
Language:	English
Published:	Taylor & Francis Group 2020-01-01
Series:	Journal of Enzyme Inhibition and Medicinal Chemistry
Subjects:	indolizine anticancer tubulin polymerisation inhibitors phenstatin pyridyl
Online Access:	http://dx.doi.org/10.1080/14756366.2020.1801671

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spelling	doaj-991624767b6e4e398dd822986eb52e4d2021-07-15T13:10:33ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742020-01-013511581159510.1080/14756366.2020.18016711801671Cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitorsMonica-Cornelia Sardaru0Anda Mihaela Craciun1Cristina-Maria Al Matarneh2Isabela Andreea Sandu3Roxana Maria Amarandi4Lacramioara Popovici5Catalina Ionica Ciobanu6Dragos Peptanariu7Mariana Pinteala8Ionel I. Mangalagiu9Ramona Danac10Department of Chemistry, Faculty of Chemistry, “Al. I. Cuza” University of IasiDepartment of Chemistry, Faculty of Chemistry, “Al. I. Cuza” University of IasiDepartment of Chemistry, Faculty of Chemistry, “Al. I. Cuza” University of Iasi“Petru Poni” Institute of Macromolecular Chemistry of Romanian AcademyDepartment of Chemistry, Faculty of Chemistry, “Al. I. Cuza” University of IasiDepartment of Chemistry, Faculty of Chemistry, “Al. I. Cuza” University of IasiResearch Department, Faculty of Chemistry, “Al. I. Cuza” University of Iasi“Petru Poni” Institute of Macromolecular Chemistry of Romanian Academy“Petru Poni” Institute of Macromolecular Chemistry of Romanian AcademyDepartment of Chemistry, Faculty of Chemistry, “Al. I. Cuza” University of IasiDepartment of Chemistry, Faculty of Chemistry, “Al. I. Cuza” University of IasiA potential microtubule destabilising series of new indolizine derivatives was synthesised and tested for their anticancer activity against a panel of 60 human cancer cell lines. Compounds 11a, 11b, 15a, and 15j showed a broad spectrum of growth inhibitory activity against cancer cell lines representing leukaemia, melanoma and cancer of lung, colon, central nervous system, ovary, kidney, breast, and prostate. Among them, compound 11a was distinguishable by its excellent cytostatic activity, showing GI50 values in the range of 10–100 nM on 43 cell lines. The less potent compounds 15a and 15j in terms of GI50 values showed a high cytotoxic effect against tested colon cancer, CNS cancer, renal cancer and melanoma cell lines and only on few cell lines from other types of cancer. In vitro assaying revealed tubulin polymerisation inhibition by all active compounds. Molecular docking showed good complementarity of active compounds with the colchicine binding site of tubulin.http://dx.doi.org/10.1080/14756366.2020.1801671indolizineanticancertubulin polymerisation inhibitorsphenstatinpyridyl
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Monica-Cornelia Sardaru Anda Mihaela Craciun Cristina-Maria Al Matarneh Isabela Andreea Sandu Roxana Maria Amarandi Lacramioara Popovici Catalina Ionica Ciobanu Dragos Peptanariu Mariana Pinteala Ionel I. Mangalagiu Ramona Danac
spellingShingle	Monica-Cornelia Sardaru Anda Mihaela Craciun Cristina-Maria Al Matarneh Isabela Andreea Sandu Roxana Maria Amarandi Lacramioara Popovici Catalina Ionica Ciobanu Dragos Peptanariu Mariana Pinteala Ionel I. Mangalagiu Ramona Danac Cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry indolizine anticancer tubulin polymerisation inhibitors phenstatin pyridyl
author_facet	Monica-Cornelia Sardaru Anda Mihaela Craciun Cristina-Maria Al Matarneh Isabela Andreea Sandu Roxana Maria Amarandi Lacramioara Popovici Catalina Ionica Ciobanu Dragos Peptanariu Mariana Pinteala Ionel I. Mangalagiu Ramona Danac
author_sort	Monica-Cornelia Sardaru
title	Cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitors
title_short	Cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitors
title_full	Cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitors
title_fullStr	Cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitors
title_full_unstemmed	Cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitors
title_sort	cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitors
publisher	Taylor & Francis Group
series	Journal of Enzyme Inhibition and Medicinal Chemistry
issn	1475-6366 1475-6374
publishDate	2020-01-01
description	A potential microtubule destabilising series of new indolizine derivatives was synthesised and tested for their anticancer activity against a panel of 60 human cancer cell lines. Compounds 11a, 11b, 15a, and 15j showed a broad spectrum of growth inhibitory activity against cancer cell lines representing leukaemia, melanoma and cancer of lung, colon, central nervous system, ovary, kidney, breast, and prostate. Among them, compound 11a was distinguishable by its excellent cytostatic activity, showing GI50 values in the range of 10–100 nM on 43 cell lines. The less potent compounds 15a and 15j in terms of GI50 values showed a high cytotoxic effect against tested colon cancer, CNS cancer, renal cancer and melanoma cell lines and only on few cell lines from other types of cancer. In vitro assaying revealed tubulin polymerisation inhibition by all active compounds. Molecular docking showed good complementarity of active compounds with the colchicine binding site of tubulin.
topic	indolizine anticancer tubulin polymerisation inhibitors phenstatin pyridyl
url	http://dx.doi.org/10.1080/14756366.2020.1801671
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Cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitors

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