Loading…
New Pyrazole/Pyrimidine-Based Scaffolds as Inhibitors of Heat Shock Protein 90 Endowed with Apoptotic Anti-Breast Cancer Activity
: Supported by a comparative study between conventional, grinding, and microwave techniques, a mild and versatile method based on the [1 + 3] cycloaddition of 2-((3-nitrophenyl)diazenyl)malononitrile to tether pyrazole and pyrimidine derivatives in good yields was used. : The newly synthesized compo...
Saved in:
| Published in: | Pharmaceuticals (Basel, Switzerland) Switzerland), 2024-09, Vol.17 (10), p.1284 |
|---|---|
| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | |
|---|---|
| cites | cdi_FETCH-LOGICAL-c429t-b944ee3296e9e1481b62adb923b04667cf78384d2e51768cac21e1ed961ae99e3 |
| container_end_page | |
| container_issue | 10 |
| container_start_page | 1284 |
| container_title | Pharmaceuticals (Basel, Switzerland) |
| container_volume | 17 |
| creator | Al-Wahaibi, Lamya H Elbastawesy, Mohammed A I Abodya, Nader E Youssif, Bahaa G M Bräse, Stefan Shabaan, Sara N Sayed, Galal H Anwer, Kurls E |
| description | : Supported by a comparative study between conventional, grinding, and microwave techniques, a mild and versatile method based on the [1 + 3] cycloaddition of 2-((3-nitrophenyl)diazenyl)malononitrile to tether pyrazole and pyrimidine derivatives in good yields was used.
: The newly synthesized compounds were analyzed with IR,
C NMR,
H NMR, mass, and elemental analysis methods. The products show interesting precursors for their antiproliferative anti-breast cancer activity.
: Pyrimidine-containing scaffold compounds
and
were the most active, achieving IC
= 26.07 and 4.72 µM against the breast cancer MCF-7 cell line, and 10.64 and 7.64 µM against breast cancer MDA-MB231-tested cell lines, respectively. Also, compounds
and
showed a remarkable inhibitory activity against the Hsp90 protein with IC
values of 2.44 and 7.30 µM, respectively, in comparison to the reference novobiocin (IC
= 1.14 µM). Moreover, there were possible apoptosis and cell cycle arrest in the G1 phase for both tested compounds (supported by CD1, caspase-3,8, BAX, and Bcl-2 studies). Also, the binding interactions of compound
were confirmed through molecular docking, and simulation studies displayed a complete overlay into the Hsp90 protein pocket.
: Compounds
and
may have apoptotic antiproliferative action as Hsp90 inhibitors. |
| doi_str_mv | 10.3390/ph17101284 |
| format | article |
| fullrecord | <record><control><sourceid>gale_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_a34b41b9539946f599f3393d74f5fb0c</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A814405411</galeid><doaj_id>oai_doaj_org_article_a34b41b9539946f599f3393d74f5fb0c</doaj_id><sourcerecordid>A814405411</sourcerecordid><originalsourceid>FETCH-LOGICAL-c429t-b944ee3296e9e1481b62adb923b04667cf78384d2e51768cac21e1ed961ae99e3</originalsourceid><addsrcrecordid>eNptkktvEzEQgFcIREvhwg9AlrggpG392odPaBsVGqmCSoWz5fWOE4eNHWynUbjxz3FIaRuEfLA1_uazZzRF8ZrgU8YEPlvNSUMwoS1_UhwTTnnZUt48fXQ-Kl7EuMC4aggnz4sjJnjVClodF78-wwZdb4P66Uc4ywe7tIN1UJ6rCAO60coYPw4RqYimbm57m3yIyBt0CSqhm7nX39F18AmsQwKjCzf4TU7c2DRH3cqvkk9Wo84lW54HUDGhiXIaAup0src2bV8Wz4waI7y620-Kbx8vvk4uy6svn6aT7qrUnIpU9oJzAEZFDQIIb0lfUzX0grIe87putGla1vKBQkWautVKUwIEBlETBUIAOymme-_g1UKucqEqbKVXVv4J-DCTKuS_jiAV4z0nvaiYELw2lRAmN5oNDTeV6bHOrg9712rdL2HQ4FJQ44H08MbZuZz5W0lIRTBlTTa8uzME_2MNMcmljRrGUTnw6ygZoQTXrG5FRt_-gy78Orjcqx2FG5ZJ_EDNVK7AOuPzw3onlV1LOMcVJyRTp_-h8hpgabV3YGyOHyS83yfo4GMMYO6LJFjupk8-TF-G3zxuyz36d9zYby870ug</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3120732100</pqid></control><display><type>article</type><title>New Pyrazole/Pyrimidine-Based Scaffolds as Inhibitors of Heat Shock Protein 90 Endowed with Apoptotic Anti-Breast Cancer Activity</title><source>Open Access: PubMed Central</source><source>Publicly Available Content Database</source><source>Coronavirus Research Database</source><creator>Al-Wahaibi, Lamya H ; Elbastawesy, Mohammed A I ; Abodya, Nader E ; Youssif, Bahaa G M ; Bräse, Stefan ; Shabaan, Sara N ; Sayed, Galal H ; Anwer, Kurls E</creator><creatorcontrib>Al-Wahaibi, Lamya H ; Elbastawesy, Mohammed A I ; Abodya, Nader E ; Youssif, Bahaa G M ; Bräse, Stefan ; Shabaan, Sara N ; Sayed, Galal H ; Anwer, Kurls E</creatorcontrib><description>: Supported by a comparative study between conventional, grinding, and microwave techniques, a mild and versatile method based on the [1 + 3] cycloaddition of 2-((3-nitrophenyl)diazenyl)malononitrile to tether pyrazole and pyrimidine derivatives in good yields was used.
: The newly synthesized compounds were analyzed with IR,
C NMR,
H NMR, mass, and elemental analysis methods. The products show interesting precursors for their antiproliferative anti-breast cancer activity.
: Pyrimidine-containing scaffold compounds
and
were the most active, achieving IC
= 26.07 and 4.72 µM against the breast cancer MCF-7 cell line, and 10.64 and 7.64 µM against breast cancer MDA-MB231-tested cell lines, respectively. Also, compounds
and
showed a remarkable inhibitory activity against the Hsp90 protein with IC
values of 2.44 and 7.30 µM, respectively, in comparison to the reference novobiocin (IC
= 1.14 µM). Moreover, there were possible apoptosis and cell cycle arrest in the G1 phase for both tested compounds (supported by CD1, caspase-3,8, BAX, and Bcl-2 studies). Also, the binding interactions of compound
were confirmed through molecular docking, and simulation studies displayed a complete overlay into the Hsp90 protein pocket.
: Compounds
and
may have apoptotic antiproliferative action as Hsp90 inhibitors.</description><identifier>ISSN: 1424-8247</identifier><identifier>EISSN: 1424-8247</identifier><identifier>DOI: 10.3390/ph17101284</identifier><identifier>PMID: 39458925</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antimitotic agents ; Antineoplastic agents ; Apoptosis ; Breast cancer ; Cancer therapies ; Cell cycle ; Drug therapy ; Ewings sarcoma ; Health aspects ; Heat shock proteins ; Hsp90 ; microwave ; Pharmaceutical research ; pyrazole ; Pyrazoles ; pyrimidine ; Pyrimidines</subject><ispartof>Pharmaceuticals (Basel, Switzerland), 2024-09, Vol.17 (10), p.1284</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 by the authors. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c429t-b944ee3296e9e1481b62adb923b04667cf78384d2e51768cac21e1ed961ae99e3</cites><orcidid>0000-0002-6834-6548 ; 0000-0002-3460-0667 ; 0000-0003-4845-3191 ; 0000-0003-3017-8806</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/3120732100/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3120732100?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,38516,43895,44590,53791,53793,74412,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39458925$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Al-Wahaibi, Lamya H</creatorcontrib><creatorcontrib>Elbastawesy, Mohammed A I</creatorcontrib><creatorcontrib>Abodya, Nader E</creatorcontrib><creatorcontrib>Youssif, Bahaa G M</creatorcontrib><creatorcontrib>Bräse, Stefan</creatorcontrib><creatorcontrib>Shabaan, Sara N</creatorcontrib><creatorcontrib>Sayed, Galal H</creatorcontrib><creatorcontrib>Anwer, Kurls E</creatorcontrib><title>New Pyrazole/Pyrimidine-Based Scaffolds as Inhibitors of Heat Shock Protein 90 Endowed with Apoptotic Anti-Breast Cancer Activity</title><title>Pharmaceuticals (Basel, Switzerland)</title><addtitle>Pharmaceuticals (Basel)</addtitle><description>: Supported by a comparative study between conventional, grinding, and microwave techniques, a mild and versatile method based on the [1 + 3] cycloaddition of 2-((3-nitrophenyl)diazenyl)malononitrile to tether pyrazole and pyrimidine derivatives in good yields was used.
: The newly synthesized compounds were analyzed with IR,
C NMR,
H NMR, mass, and elemental analysis methods. The products show interesting precursors for their antiproliferative anti-breast cancer activity.
: Pyrimidine-containing scaffold compounds
and
were the most active, achieving IC
= 26.07 and 4.72 µM against the breast cancer MCF-7 cell line, and 10.64 and 7.64 µM against breast cancer MDA-MB231-tested cell lines, respectively. Also, compounds
and
showed a remarkable inhibitory activity against the Hsp90 protein with IC
values of 2.44 and 7.30 µM, respectively, in comparison to the reference novobiocin (IC
= 1.14 µM). Moreover, there were possible apoptosis and cell cycle arrest in the G1 phase for both tested compounds (supported by CD1, caspase-3,8, BAX, and Bcl-2 studies). Also, the binding interactions of compound
were confirmed through molecular docking, and simulation studies displayed a complete overlay into the Hsp90 protein pocket.
: Compounds
and
may have apoptotic antiproliferative action as Hsp90 inhibitors.</description><subject>Antimitotic agents</subject><subject>Antineoplastic agents</subject><subject>Apoptosis</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Drug therapy</subject><subject>Ewings sarcoma</subject><subject>Health aspects</subject><subject>Heat shock proteins</subject><subject>Hsp90</subject><subject>microwave</subject><subject>Pharmaceutical research</subject><subject>pyrazole</subject><subject>Pyrazoles</subject><subject>pyrimidine</subject><subject>Pyrimidines</subject><issn>1424-8247</issn><issn>1424-8247</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>COVID</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkktvEzEQgFcIREvhwg9AlrggpG392odPaBsVGqmCSoWz5fWOE4eNHWynUbjxz3FIaRuEfLA1_uazZzRF8ZrgU8YEPlvNSUMwoS1_UhwTTnnZUt48fXQ-Kl7EuMC4aggnz4sjJnjVClodF78-wwZdb4P66Uc4ywe7tIN1UJ6rCAO60coYPw4RqYimbm57m3yIyBt0CSqhm7nX39F18AmsQwKjCzf4TU7c2DRH3cqvkk9Wo84lW54HUDGhiXIaAup0src2bV8Wz4waI7y620-Kbx8vvk4uy6svn6aT7qrUnIpU9oJzAEZFDQIIb0lfUzX0grIe87putGla1vKBQkWautVKUwIEBlETBUIAOymme-_g1UKucqEqbKVXVv4J-DCTKuS_jiAV4z0nvaiYELw2lRAmN5oNDTeV6bHOrg9712rdL2HQ4FJQ44H08MbZuZz5W0lIRTBlTTa8uzME_2MNMcmljRrGUTnw6ygZoQTXrG5FRt_-gy78Orjcqx2FG5ZJ_EDNVK7AOuPzw3onlV1LOMcVJyRTp_-h8hpgabV3YGyOHyS83yfo4GMMYO6LJFjupk8-TF-G3zxuyz36d9zYby870ug</recordid><startdate>20240927</startdate><enddate>20240927</enddate><creator>Al-Wahaibi, Lamya H</creator><creator>Elbastawesy, Mohammed A I</creator><creator>Abodya, Nader E</creator><creator>Youssif, Bahaa G M</creator><creator>Bräse, Stefan</creator><creator>Shabaan, Sara N</creator><creator>Sayed, Galal H</creator><creator>Anwer, Kurls E</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7XB</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-6834-6548</orcidid><orcidid>https://orcid.org/0000-0002-3460-0667</orcidid><orcidid>https://orcid.org/0000-0003-4845-3191</orcidid><orcidid>https://orcid.org/0000-0003-3017-8806</orcidid></search><sort><creationdate>20240927</creationdate><title>New Pyrazole/Pyrimidine-Based Scaffolds as Inhibitors of Heat Shock Protein 90 Endowed with Apoptotic Anti-Breast Cancer Activity</title><author>Al-Wahaibi, Lamya H ; Elbastawesy, Mohammed A I ; Abodya, Nader E ; Youssif, Bahaa G M ; Bräse, Stefan ; Shabaan, Sara N ; Sayed, Galal H ; Anwer, Kurls E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-b944ee3296e9e1481b62adb923b04667cf78384d2e51768cac21e1ed961ae99e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Antimitotic agents</topic><topic>Antineoplastic agents</topic><topic>Apoptosis</topic><topic>Breast cancer</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Drug therapy</topic><topic>Ewings sarcoma</topic><topic>Health aspects</topic><topic>Heat shock proteins</topic><topic>Hsp90</topic><topic>microwave</topic><topic>Pharmaceutical research</topic><topic>pyrazole</topic><topic>Pyrazoles</topic><topic>pyrimidine</topic><topic>Pyrimidines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Al-Wahaibi, Lamya H</creatorcontrib><creatorcontrib>Elbastawesy, Mohammed A I</creatorcontrib><creatorcontrib>Abodya, Nader E</creatorcontrib><creatorcontrib>Youssif, Bahaa G M</creatorcontrib><creatorcontrib>Bräse, Stefan</creatorcontrib><creatorcontrib>Shabaan, Sara N</creatorcontrib><creatorcontrib>Sayed, Galal H</creatorcontrib><creatorcontrib>Anwer, Kurls E</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Pharmaceuticals (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Al-Wahaibi, Lamya H</au><au>Elbastawesy, Mohammed A I</au><au>Abodya, Nader E</au><au>Youssif, Bahaa G M</au><au>Bräse, Stefan</au><au>Shabaan, Sara N</au><au>Sayed, Galal H</au><au>Anwer, Kurls E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New Pyrazole/Pyrimidine-Based Scaffolds as Inhibitors of Heat Shock Protein 90 Endowed with Apoptotic Anti-Breast Cancer Activity</atitle><jtitle>Pharmaceuticals (Basel, Switzerland)</jtitle><addtitle>Pharmaceuticals (Basel)</addtitle><date>2024-09-27</date><risdate>2024</risdate><volume>17</volume><issue>10</issue><spage>1284</spage><pages>1284-</pages><issn>1424-8247</issn><eissn>1424-8247</eissn><abstract>: Supported by a comparative study between conventional, grinding, and microwave techniques, a mild and versatile method based on the [1 + 3] cycloaddition of 2-((3-nitrophenyl)diazenyl)malononitrile to tether pyrazole and pyrimidine derivatives in good yields was used.
: The newly synthesized compounds were analyzed with IR,
C NMR,
H NMR, mass, and elemental analysis methods. The products show interesting precursors for their antiproliferative anti-breast cancer activity.
: Pyrimidine-containing scaffold compounds
and
were the most active, achieving IC
= 26.07 and 4.72 µM against the breast cancer MCF-7 cell line, and 10.64 and 7.64 µM against breast cancer MDA-MB231-tested cell lines, respectively. Also, compounds
and
showed a remarkable inhibitory activity against the Hsp90 protein with IC
values of 2.44 and 7.30 µM, respectively, in comparison to the reference novobiocin (IC
= 1.14 µM). Moreover, there were possible apoptosis and cell cycle arrest in the G1 phase for both tested compounds (supported by CD1, caspase-3,8, BAX, and Bcl-2 studies). Also, the binding interactions of compound
were confirmed through molecular docking, and simulation studies displayed a complete overlay into the Hsp90 protein pocket.
: Compounds
and
may have apoptotic antiproliferative action as Hsp90 inhibitors.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>39458925</pmid><doi>10.3390/ph17101284</doi><orcidid>https://orcid.org/0000-0002-6834-6548</orcidid><orcidid>https://orcid.org/0000-0002-3460-0667</orcidid><orcidid>https://orcid.org/0000-0003-4845-3191</orcidid><orcidid>https://orcid.org/0000-0003-3017-8806</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1424-8247 |
| ispartof | Pharmaceuticals (Basel, Switzerland), 2024-09, Vol.17 (10), p.1284 |
| issn | 1424-8247 1424-8247 |
| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_a34b41b9539946f599f3393d74f5fb0c |
| source | Open Access: PubMed Central; Publicly Available Content Database; Coronavirus Research Database |
| subjects | Antimitotic agents Antineoplastic agents Apoptosis Breast cancer Cancer therapies Cell cycle Drug therapy Ewings sarcoma Health aspects Heat shock proteins Hsp90 microwave Pharmaceutical research pyrazole Pyrazoles pyrimidine Pyrimidines |
| title | New Pyrazole/Pyrimidine-Based Scaffolds as Inhibitors of Heat Shock Protein 90 Endowed with Apoptotic Anti-Breast Cancer Activity |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T19%3A17%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=New%20Pyrazole/Pyrimidine-Based%20Scaffolds%20as%20Inhibitors%20of%20Heat%20Shock%20Protein%2090%20Endowed%20with%20Apoptotic%20Anti-Breast%20Cancer%20Activity&rft.jtitle=Pharmaceuticals%20(Basel,%20Switzerland)&rft.au=Al-Wahaibi,%20Lamya%20H&rft.date=2024-09-27&rft.volume=17&rft.issue=10&rft.spage=1284&rft.pages=1284-&rft.issn=1424-8247&rft.eissn=1424-8247&rft_id=info:doi/10.3390/ph17101284&rft_dat=%3Cgale_doaj_%3EA814405411%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c429t-b944ee3296e9e1481b62adb923b04667cf78384d2e51768cac21e1ed961ae99e3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=3120732100&rft_id=info:pmid/39458925&rft_galeid=A814405411&rfr_iscdi=true |