Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents

Background and purpose: In this study, some new cytotoxic hybrid structures were synthesized by combining pyrazolinone and imidazolinone rings with quinazoline pharmacophores. Experimental approach: The benzoxazinone, pyrazolo-quinazoline fused ring, and imidazolinone anchored quinazoline derivative...

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Autores principales:	Mahla Malekzadeh, Shadi Dadkhah, Ghadam Ali Khodarahmi, Parvin Asadi, Farshid Hassanzadeh, Mahboubeh Rostami
Formato:	article
Lenguaje:	EN
Publicado:	Wolters Kluwer Medknow Publications 2022
Materias:	anticancer activity; molecular docking; oxazolone; pyrazoline; quinizolinone. Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/28a388f9912349bfafe810bf3a70327d
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spelling	oai:doaj.org-article:28a388f9912349bfafe810bf3a70327d2021-11-19T12:17:03ZSome novel hybrid quinazoline-based heterocycles as potent cytotoxic agents1735-53621735-941410.4103/1735-5362.329923https://doaj.org/article/28a388f9912349bfafe810bf3a70327d2022-01-01T00:00:00Zhttp://www.rpsjournal.net/article.asp?issn=1735-5362;year=2022;volume=17;issue=1;spage=22;epage=34;aulast=Malekzadehhttps://doaj.org/toc/1735-5362https://doaj.org/toc/1735-9414Background and purpose: In this study, some new cytotoxic hybrid structures were synthesized by combining pyrazolinone and imidazolinone rings with quinazoline pharmacophores. Experimental approach: The benzoxazinone, pyrazolo-quinazoline fused ring, and imidazolinone anchored quinazoline derivatives were synthesized by simple ring-opening, ring expansion, and ring closure strategies from oxazolones. The molecular docking studies of the final derivatives were accomplished on the epidermal growth factor receptor enzyme. The cytotoxic effect of the final compounds on the MCF-7 cell line was evaluated by MTT assay. Findings/Results: The docking results confirmed the optimized electrostatic, H-bonding, and hydrophobic interactions of structures with the key residues of the active site (ΔGbin < -9Kcal/mol). The derivatives have been obtained in good yield and purity, and their structures were confirmed by different methods (FT-IR, 1H-NMR, 13C-NMR, and CHNS analysis). The IC50s of all final derivatives against the MCF-7 cell line were lower than 10 μM, and between all, the IXa from pyrazolo-quinazolinone class (IC50: 6.43 μM) with chlorine substitute was the most potent. Furthermore, all derivatives showed negligible cytotoxicity on HUVEC normal cell line which would be a great achievement for a novel cytotoxic agent. Conclusion and implications: Based on the obtained results, pyrazolo[1,5-c] quinazolin-2-one series were more cytotoxic than imidazolinone methyl quinazoline-4(3H)-ones against MCF-7 cells. Chlorine substitute in the para position of the aromatic ring improved the cytotoxicity effect in both classes. It could be related to the polarizability of a chlorine atom and making better intermolecular interactions. Further pre-clinical evaluations are required for the promising synthesized cytotoxic compounds.Mahla MalekzadehShadi DadkhahGhadam Ali KhodarahmiParvin AsadiFarshid HassanzadehMahboubeh RostamiWolters Kluwer Medknow Publicationsarticleanticancer activity; molecular docking; oxazolone; pyrazoline; quinizolinone.Pharmacy and materia medicaRS1-441ENResearch in Pharmaceutical Sciences, Vol 17, Iss 1, Pp 22-34 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	anticancer activity; molecular docking; oxazolone; pyrazoline; quinizolinone. Pharmacy and materia medica RS1-441
spellingShingle	anticancer activity; molecular docking; oxazolone; pyrazoline; quinizolinone. Pharmacy and materia medica RS1-441 Mahla Malekzadeh Shadi Dadkhah Ghadam Ali Khodarahmi Parvin Asadi Farshid Hassanzadeh Mahboubeh Rostami Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents
description	Background and purpose: In this study, some new cytotoxic hybrid structures were synthesized by combining pyrazolinone and imidazolinone rings with quinazoline pharmacophores. Experimental approach: The benzoxazinone, pyrazolo-quinazoline fused ring, and imidazolinone anchored quinazoline derivatives were synthesized by simple ring-opening, ring expansion, and ring closure strategies from oxazolones. The molecular docking studies of the final derivatives were accomplished on the epidermal growth factor receptor enzyme. The cytotoxic effect of the final compounds on the MCF-7 cell line was evaluated by MTT assay. Findings/Results: The docking results confirmed the optimized electrostatic, H-bonding, and hydrophobic interactions of structures with the key residues of the active site (ΔGbin < -9Kcal/mol). The derivatives have been obtained in good yield and purity, and their structures were confirmed by different methods (FT-IR, 1H-NMR, 13C-NMR, and CHNS analysis). The IC50s of all final derivatives against the MCF-7 cell line were lower than 10 μM, and between all, the IXa from pyrazolo-quinazolinone class (IC50: 6.43 μM) with chlorine substitute was the most potent. Furthermore, all derivatives showed negligible cytotoxicity on HUVEC normal cell line which would be a great achievement for a novel cytotoxic agent. Conclusion and implications: Based on the obtained results, pyrazolo[1,5-c] quinazolin-2-one series were more cytotoxic than imidazolinone methyl quinazoline-4(3H)-ones against MCF-7 cells. Chlorine substitute in the para position of the aromatic ring improved the cytotoxicity effect in both classes. It could be related to the polarizability of a chlorine atom and making better intermolecular interactions. Further pre-clinical evaluations are required for the promising synthesized cytotoxic compounds.
format	article
author	Mahla Malekzadeh Shadi Dadkhah Ghadam Ali Khodarahmi Parvin Asadi Farshid Hassanzadeh Mahboubeh Rostami
author_facet	Mahla Malekzadeh Shadi Dadkhah Ghadam Ali Khodarahmi Parvin Asadi Farshid Hassanzadeh Mahboubeh Rostami
author_sort	Mahla Malekzadeh
title	Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents
title_short	Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents
title_full	Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents
title_fullStr	Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents
title_full_unstemmed	Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents
title_sort	some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents
publisher	Wolters Kluwer Medknow Publications
publishDate	2022
url	https://doaj.org/article/28a388f9912349bfafe810bf3a70327d
work_keys_str_mv	AT mahlamalekzadeh somenovelhybridquinazolinebasedheterocyclesaspotentcytotoxicagents AT shadidadkhah somenovelhybridquinazolinebasedheterocyclesaspotentcytotoxicagents AT ghadamalikhodarahmi somenovelhybridquinazolinebasedheterocyclesaspotentcytotoxicagents AT parvinasadi somenovelhybridquinazolinebasedheterocyclesaspotentcytotoxicagents AT farshidhassanzadeh somenovelhybridquinazolinebasedheterocyclesaspotentcytotoxicagents AT mahboubehrostami somenovelhybridquinazolinebasedheterocyclesaspotentcytotoxicagents
_version_	1718420060377186304

Some novel hybrid quinazoline-based heterocycles as potent cytotoxic agents

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