Design, synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitors

New target compounds were designed as inhibitors of tubulin polymerization relying on using two types of ring B models (cyclohexenone and indazole) to replace the central ring in colchicine. Different functional groups (R1) were attached to manipulate their physicochemical properties and/or their bi...

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Main Authors:	Riham I. Ahmed, Essam Eldin A. Osman, Fadi M. Awadallah, Samir M. El-Moghazy
Format:	Article
Language:	English
Published:	Taylor & Francis Group 2017-01-01
Series:	Journal of Enzyme Inhibition and Medicinal Chemistry
Subjects:	Antimitotic agent cell cycle colchicine docking tubulin
Online Access:	http://dx.doi.org/10.1080/14756366.2016.1244532

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spelling	doaj-c2d6dbbe02d64e02b6baa7b47f4a60f32020-11-24T21:47:05ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742017-01-0132117618810.1080/14756366.2016.12445321244532Design, synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitorsRiham I. Ahmed0Essam Eldin A. Osman1Fadi M. Awadallah2Samir M. El-Moghazy3Nahda University in Beni SuefCairo UniversityCairo UniversityCairo UniversityNew target compounds were designed as inhibitors of tubulin polymerization relying on using two types of ring B models (cyclohexenone and indazole) to replace the central ring in colchicine. Different functional groups (R1) were attached to manipulate their physicochemical properties and/or their biological activity. The designed compounds were assessed for their antitumor activity on HCT-116 and MCF-7 cancer cell lines. Compounds 4b, 5e and 5f exhibited comparable or higher potency than colchicine against colon HCT-116 and MCF-7 tumor cells. The mechanism of the antitumor activity was investigated through evaluating the tubulin inhibition potential of the active compounds. Compounds 4b, 5e and 5f showed percentage inhibition of tubulin in both cell line homogenates ranging from 79.72% to 89.31%. Cell cycle analysis of compounds 4b, 5e and 5f revealed cell cycle arrest at G2/M phase. Molecular docking revealed the binding mode of these new compounds into the colchicine binding site of tubulin.http://dx.doi.org/10.1080/14756366.2016.1244532Antimitotic agentcell cyclecolchicinedockingtubulin
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Riham I. Ahmed Essam Eldin A. Osman Fadi M. Awadallah Samir M. El-Moghazy
spellingShingle	Riham I. Ahmed Essam Eldin A. Osman Fadi M. Awadallah Samir M. El-Moghazy Design, synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry Antimitotic agent cell cycle colchicine docking tubulin
author_facet	Riham I. Ahmed Essam Eldin A. Osman Fadi M. Awadallah Samir M. El-Moghazy
author_sort	Riham I. Ahmed
title	Design, synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitors
title_short	Design, synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitors
title_full	Design, synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitors
title_fullStr	Design, synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitors
title_full_unstemmed	Design, synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitors
title_sort	design, synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitors
publisher	Taylor & Francis Group
series	Journal of Enzyme Inhibition and Medicinal Chemistry
issn	1475-6366 1475-6374
publishDate	2017-01-01
description	New target compounds were designed as inhibitors of tubulin polymerization relying on using two types of ring B models (cyclohexenone and indazole) to replace the central ring in colchicine. Different functional groups (R1) were attached to manipulate their physicochemical properties and/or their biological activity. The designed compounds were assessed for their antitumor activity on HCT-116 and MCF-7 cancer cell lines. Compounds 4b, 5e and 5f exhibited comparable or higher potency than colchicine against colon HCT-116 and MCF-7 tumor cells. The mechanism of the antitumor activity was investigated through evaluating the tubulin inhibition potential of the active compounds. Compounds 4b, 5e and 5f showed percentage inhibition of tubulin in both cell line homogenates ranging from 79.72% to 89.31%. Cell cycle analysis of compounds 4b, 5e and 5f revealed cell cycle arrest at G2/M phase. Molecular docking revealed the binding mode of these new compounds into the colchicine binding site of tubulin.
topic	Antimitotic agent cell cycle colchicine docking tubulin
url	http://dx.doi.org/10.1080/14756366.2016.1244532
work_keys_str_mv	AT rihamiahmed designsynthesisandmoleculardockingofnoveldiarylcyclohexenoneanddiarylindazolederivativesastubulinpolymerizationinhibitors AT essameldinaosman designsynthesisandmoleculardockingofnoveldiarylcyclohexenoneanddiarylindazolederivativesastubulinpolymerizationinhibitors AT fadimawadallah designsynthesisandmoleculardockingofnoveldiarylcyclohexenoneanddiarylindazolederivativesastubulinpolymerizationinhibitors AT samirmelmoghazy designsynthesisandmoleculardockingofnoveldiarylcyclohexenoneanddiarylindazolederivativesastubulinpolymerizationinhibitors
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Design, synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitors

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