In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one Candidates

In this study, some of new thiophenyl thienopyrimidinone derivatives 2−15 were prepared and tested as anti-cancer agents by using thiophenyl thieno[2,3-d]pyrimidinone derivative 2 as a starting material, which was prepared from cycli...

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Main Authors:	Abd El-Galil E. Amr, Alhussein A. Ibrahimd, Mohamed F. El-Shehry, Hanaa M. Hosni, Ahmed A. Fayed, Elsayed A. Elsayed
Format:	Article
Language:	English
Published:	MDPI AG 2019-06-01
Series:	Molecules
Subjects:	thiopene thienopyrimidinone thiazolidinone anticancer activity
Online Access:	https://www.mdpi.com/1420-3049/24/12/2255

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spelling	doaj-5c69d36c7ef94e0b9a13de0bb7c2a9e12020-11-25T01:11:16ZengMDPI AGMolecules1420-30492019-06-012412225510.3390/molecules24122255molecules24122255In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one CandidatesAbd El-Galil E. Amr0Alhussein A. Ibrahimd1Mohamed F. El-Shehry2Hanaa M. Hosni3Ahmed A. Fayed4Elsayed A. Elsayed5Pharmaceutical Chemistry Department, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaApplied Organic Chemistry Department, National Research Center, Cairo, Dokki 12622, EgyptPesticide Chemistry Department, National Research Center, Dokki 12622, Cairo, EgyptPesticide Chemistry Department, National Research Center, Dokki 12622, Cairo, EgyptApplied Organic Chemistry Department, National Research Center, Cairo, Dokki 12622, EgyptZoology Department, Bioproducts Research Chair, Faculty of Science, King Saud University, Riyadh 11451, Saudi ArabiaIn this study, some of new thiophenyl thienopyrimidinone derivatives <b>2</b>−<b>15</b> were prepared and tested as anti-cancer agents by using thiophenyl thieno[2,3-d]pyrimidinone derivative <b>2</b> as a starting material, which was prepared from cyclization of ethyl ester derivative <b>1</b> with formamide. Treatment of <b>2</b> with ethyl- chloroacetate gave thienopyrimidinone <i>N</i>-ethylacetate <b>3</b>, which was reacted with hydrazine hydrate or anthranilic acid to afford acetohydrazide <b>4</b> and benzo[d][1,<sup>3</sup>]oxazin-4-one <b>5,</b> respectively. Condensation of <b>4</b> with aromatic aldehydes or phenylisothiocyanate yielded Schiff base derivatives <b>6,7</b>, and thiosemicarbazise <b>10</b>, which were treated with 2-mercaptoacetic acid or chloroacetic acid to give the corresponding thiazolidinones <b>8</b>, <b>9,</b> and phenylimino-thiazolidinone <b>11</b>, respectively. Treatment of <b>4</b> with ethylacetoacetate or acetic acid/acetic anhydride gave pyrazole <b>12</b> and acetyl acetohydrazide <b>13</b> derivatives, respectively. The latter compound <b>13</b> was reacted with ethyl cycno-acetate or malononitrile to give <b>14</b> and <b>15</b>, respectively. In this work, we have studied the anti-cancer activity of the synthesized thienopyrimidinone derivatives against MCF-7 and MCF-10A cancer cells. Furthermore, in vivo experiments showed that the synthesized compounds significantly reduced tumor growth up to the 8<sup>th</sup> day of treatment in comparison to control animal models. Additionally, the synthesized derivatives showed potential inhibitory effects against pim-1 kinase activities.https://www.mdpi.com/1420-3049/24/12/2255thiopenethienopyrimidinonethiazolidinoneanticancer activity
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Abd El-Galil E. Amr Alhussein A. Ibrahimd Mohamed F. El-Shehry Hanaa M. Hosni Ahmed A. Fayed Elsayed A. Elsayed
spellingShingle	Abd El-Galil E. Amr Alhussein A. Ibrahimd Mohamed F. El-Shehry Hanaa M. Hosni Ahmed A. Fayed Elsayed A. Elsayed In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one Candidates Molecules thiopene thienopyrimidinone thiazolidinone anticancer activity
author_facet	Abd El-Galil E. Amr Alhussein A. Ibrahimd Mohamed F. El-Shehry Hanaa M. Hosni Ahmed A. Fayed Elsayed A. Elsayed
author_sort	Abd El-Galil E. Amr
title	In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one Candidates
title_short	In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one Candidates
title_full	In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one Candidates
title_fullStr	In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one Candidates
title_full_unstemmed	In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one Candidates
title_sort	in vitro and in vivo anti-breast cancer activities of some newly synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one candidates
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2019-06-01
description	In this study, some of new thiophenyl thienopyrimidinone derivatives <b>2</b>−<b>15</b> were prepared and tested as anti-cancer agents by using thiophenyl thieno[2,3-d]pyrimidinone derivative <b>2</b> as a starting material, which was prepared from cyclization of ethyl ester derivative <b>1</b> with formamide. Treatment of <b>2</b> with ethyl- chloroacetate gave thienopyrimidinone <i>N</i>-ethylacetate <b>3</b>, which was reacted with hydrazine hydrate or anthranilic acid to afford acetohydrazide <b>4</b> and benzo[d][1,<sup>3</sup>]oxazin-4-one <b>5,</b> respectively. Condensation of <b>4</b> with aromatic aldehydes or phenylisothiocyanate yielded Schiff base derivatives <b>6,7</b>, and thiosemicarbazise <b>10</b>, which were treated with 2-mercaptoacetic acid or chloroacetic acid to give the corresponding thiazolidinones <b>8</b>, <b>9,</b> and phenylimino-thiazolidinone <b>11</b>, respectively. Treatment of <b>4</b> with ethylacetoacetate or acetic acid/acetic anhydride gave pyrazole <b>12</b> and acetyl acetohydrazide <b>13</b> derivatives, respectively. The latter compound <b>13</b> was reacted with ethyl cycno-acetate or malononitrile to give <b>14</b> and <b>15</b>, respectively. In this work, we have studied the anti-cancer activity of the synthesized thienopyrimidinone derivatives against MCF-7 and MCF-10A cancer cells. Furthermore, in vivo experiments showed that the synthesized compounds significantly reduced tumor growth up to the 8<sup>th</sup> day of treatment in comparison to control animal models. Additionally, the synthesized derivatives showed potential inhibitory effects against pim-1 kinase activities.
topic	thiopene thienopyrimidinone thiazolidinone anticancer activity
url	https://www.mdpi.com/1420-3049/24/12/2255
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In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one Candidates

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