One-pot synthesis and antiproliferative activity of novel 2,4-diaminopyrimidine derivatives bearing piperidine and piperazine moieties
A series of novel 2,4-diaminopyrimidines containing piperidine and piperazine moieties were synthesized via an efficient one-pot methodology. The bioassay tests demonstrated that compounds 27 and 28 displayed much stronger antitumor activities against four human cancer cell lines (HepG2, A549, MDA-M...
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| Veröffentlicht in: | European journal of medicinal chemistry 2014-09, Vol.84, p.127-134 |
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| container_title | European journal of medicinal chemistry |
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| creator | Ma, Wei-Feng Yang, Hai-Kui Hu, Meng-Jin Li, Qian Ma, Tian-Zhu Zhou, Zhong-Zhen Liu, Rui-Yuan You, Wen-Wei Zhao, Pei-Liang |
| description | A series of novel 2,4-diaminopyrimidines containing piperidine and piperazine moieties were synthesized via an efficient one-pot methodology. The bioassay tests demonstrated that compounds 27 and 28 displayed much stronger antitumor activities against four human cancer cell lines (HepG2, A549, MDA-MB-231 and MCF-7) than positive control fluorouracil. Particularly, compound 28 showed a two-fold improvement compared to fluorouracil in inhibiting MDA-MB-231 and A549 cell proliferation with IC50 values of 7.46 and 12.78 μM, respectively. Further flow-activated cell sorting analysis revealed that the most promising compound 28 displayed a significant effect on G2/M cell-cycle arrest in a dose-dependent manner in MDA-MB-231 cells.
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•24 novel 2,4-diaminopyrimidines were synthesized via a one-pot reaction.•Antiproliferative activity of these compounds was evaluated.•Two compounds displayed much stronger antitumor activity than Fluorouracil.•Compound 28 displayed a significant effect on G2/M cell-cycle arrest in MDA-MB-231. |
| doi_str_mv | 10.1016/j.ejmech.2014.07.017 |
| format | Article |
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[Display omitted]
•24 novel 2,4-diaminopyrimidines were synthesized via a one-pot reaction.•Antiproliferative activity of these compounds was evaluated.•Two compounds displayed much stronger antitumor activity than Fluorouracil.•Compound 28 displayed a significant effect on G2/M cell-cycle arrest in MDA-MB-231.</description><identifier>ISSN: 0223-5234</identifier><identifier>EISSN: 1768-3254</identifier><identifier>DOI: 10.1016/j.ejmech.2014.07.017</identifier><identifier>PMID: 25016234</identifier><language>eng</language><publisher>France: Elsevier Masson SAS</publisher><subject>2,4-Diaminopyrimidines ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - isolation & purification ; Antineoplastic Agents - pharmacology ; Antiproliferative activity ; Cell Cycle - drug effects ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Hep G2 Cells ; Humans ; MCF-7 Cells ; Molecular Structure ; One-pot synthesis ; Piperazine ; Piperazines - chemistry ; Piperidine ; Piperidines - chemistry ; Pyrimidines - chemical synthesis ; Pyrimidines - chemistry ; Pyrimidines - pharmacology ; Structure-Activity Relationship</subject><ispartof>European journal of medicinal chemistry, 2014-09, Vol.84, p.127-134</ispartof><rights>2014 Elsevier Masson SAS</rights><rights>Copyright © 2014 Elsevier Masson SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-b32053e70afeecf6eb0cc9673d791a525cfa73f3d6c66bdf1bb53c8fd5ed0fbf3</citedby><cites>FETCH-LOGICAL-c428t-b32053e70afeecf6eb0cc9673d791a525cfa73f3d6c66bdf1bb53c8fd5ed0fbf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejmech.2014.07.017$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25016234$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Wei-Feng</creatorcontrib><creatorcontrib>Yang, Hai-Kui</creatorcontrib><creatorcontrib>Hu, Meng-Jin</creatorcontrib><creatorcontrib>Li, Qian</creatorcontrib><creatorcontrib>Ma, Tian-Zhu</creatorcontrib><creatorcontrib>Zhou, Zhong-Zhen</creatorcontrib><creatorcontrib>Liu, Rui-Yuan</creatorcontrib><creatorcontrib>You, Wen-Wei</creatorcontrib><creatorcontrib>Zhao, Pei-Liang</creatorcontrib><title>One-pot synthesis and antiproliferative activity of novel 2,4-diaminopyrimidine derivatives bearing piperidine and piperazine moieties</title><title>European journal of medicinal chemistry</title><addtitle>Eur J Med Chem</addtitle><description>A series of novel 2,4-diaminopyrimidines containing piperidine and piperazine moieties were synthesized via an efficient one-pot methodology. The bioassay tests demonstrated that compounds 27 and 28 displayed much stronger antitumor activities against four human cancer cell lines (HepG2, A549, MDA-MB-231 and MCF-7) than positive control fluorouracil. Particularly, compound 28 showed a two-fold improvement compared to fluorouracil in inhibiting MDA-MB-231 and A549 cell proliferation with IC50 values of 7.46 and 12.78 μM, respectively. Further flow-activated cell sorting analysis revealed that the most promising compound 28 displayed a significant effect on G2/M cell-cycle arrest in a dose-dependent manner in MDA-MB-231 cells.
[Display omitted]
•24 novel 2,4-diaminopyrimidines were synthesized via a one-pot reaction.•Antiproliferative activity of these compounds was evaluated.•Two compounds displayed much stronger antitumor activity than Fluorouracil.•Compound 28 displayed a significant effect on G2/M cell-cycle arrest in MDA-MB-231.</description><subject>2,4-Diaminopyrimidines</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - isolation & purification</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antiproliferative activity</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>MCF-7 Cells</subject><subject>Molecular Structure</subject><subject>One-pot synthesis</subject><subject>Piperazine</subject><subject>Piperazines - chemistry</subject><subject>Piperidine</subject><subject>Piperidines - chemistry</subject><subject>Pyrimidines - chemical synthesis</subject><subject>Pyrimidines - chemistry</subject><subject>Pyrimidines - pharmacology</subject><subject>Structure-Activity Relationship</subject><issn>0223-5234</issn><issn>1768-3254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UctuFDEQtBARWRb-ACEfOTATP8bjzQUJRbykSLnA2fLYbdKrGc9ge1fafEC-O97dwJGD1ep2dZWqi5B3nLWc8f5q28J2AnffCsa7lumWcf2CrLjuN40UqntJVkwI2Sghu0vyOuctY0z1jL0il0JVhjpfkce7CM0yF5oPsdxDxkxt9PUVXNI8YoBkC-6BWlcLlgOdA43zHkYqPnaNRzthnJdDwgk9RqAeEu5PK5kOYBPG33TBpU5P30fyU2sfju00IxSE_IZcBDtmePtc1-TX1y8_b743t3ffftx8vm1cJzalGaRgSoJmNgC40MPAnLvutfT6mlsllAtWyyB97_p-8IEPg5JuE7wCz8IQ5Jp8OPNWc392kIuZMDsYRxth3mXDleo6LXRVWZPuDHVpzjlBMEs1adPBcGaOCZitOSdgjgkYpk1NoK69f1bYDRP4f0t_T14Bn84AqD73CMlkhxAdeEzgivEz_l_hCY56nf4</recordid><startdate>20140912</startdate><enddate>20140912</enddate><creator>Ma, Wei-Feng</creator><creator>Yang, Hai-Kui</creator><creator>Hu, Meng-Jin</creator><creator>Li, Qian</creator><creator>Ma, Tian-Zhu</creator><creator>Zhou, Zhong-Zhen</creator><creator>Liu, Rui-Yuan</creator><creator>You, Wen-Wei</creator><creator>Zhao, Pei-Liang</creator><general>Elsevier Masson SAS</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20140912</creationdate><title>One-pot synthesis and antiproliferative activity of novel 2,4-diaminopyrimidine derivatives bearing piperidine and piperazine moieties</title><author>Ma, Wei-Feng ; Yang, Hai-Kui ; Hu, Meng-Jin ; Li, Qian ; Ma, Tian-Zhu ; Zhou, Zhong-Zhen ; Liu, Rui-Yuan ; You, Wen-Wei ; Zhao, Pei-Liang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-b32053e70afeecf6eb0cc9673d791a525cfa73f3d6c66bdf1bb53c8fd5ed0fbf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>2,4-Diaminopyrimidines</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - isolation & purification</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antiproliferative activity</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Hep G2 Cells</topic><topic>Humans</topic><topic>MCF-7 Cells</topic><topic>Molecular Structure</topic><topic>One-pot synthesis</topic><topic>Piperazine</topic><topic>Piperazines - chemistry</topic><topic>Piperidine</topic><topic>Piperidines - chemistry</topic><topic>Pyrimidines - chemical synthesis</topic><topic>Pyrimidines - chemistry</topic><topic>Pyrimidines - pharmacology</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Wei-Feng</creatorcontrib><creatorcontrib>Yang, Hai-Kui</creatorcontrib><creatorcontrib>Hu, Meng-Jin</creatorcontrib><creatorcontrib>Li, Qian</creatorcontrib><creatorcontrib>Ma, Tian-Zhu</creatorcontrib><creatorcontrib>Zhou, Zhong-Zhen</creatorcontrib><creatorcontrib>Liu, Rui-Yuan</creatorcontrib><creatorcontrib>You, Wen-Wei</creatorcontrib><creatorcontrib>Zhao, Pei-Liang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Wei-Feng</au><au>Yang, Hai-Kui</au><au>Hu, Meng-Jin</au><au>Li, Qian</au><au>Ma, Tian-Zhu</au><au>Zhou, Zhong-Zhen</au><au>Liu, Rui-Yuan</au><au>You, Wen-Wei</au><au>Zhao, Pei-Liang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>One-pot synthesis and antiproliferative activity of novel 2,4-diaminopyrimidine derivatives bearing piperidine and piperazine moieties</atitle><jtitle>European journal of medicinal chemistry</jtitle><addtitle>Eur J Med Chem</addtitle><date>2014-09-12</date><risdate>2014</risdate><volume>84</volume><spage>127</spage><epage>134</epage><pages>127-134</pages><issn>0223-5234</issn><eissn>1768-3254</eissn><abstract>A series of novel 2,4-diaminopyrimidines containing piperidine and piperazine moieties were synthesized via an efficient one-pot methodology. The bioassay tests demonstrated that compounds 27 and 28 displayed much stronger antitumor activities against four human cancer cell lines (HepG2, A549, MDA-MB-231 and MCF-7) than positive control fluorouracil. Particularly, compound 28 showed a two-fold improvement compared to fluorouracil in inhibiting MDA-MB-231 and A549 cell proliferation with IC50 values of 7.46 and 12.78 μM, respectively. Further flow-activated cell sorting analysis revealed that the most promising compound 28 displayed a significant effect on G2/M cell-cycle arrest in a dose-dependent manner in MDA-MB-231 cells.
[Display omitted]
•24 novel 2,4-diaminopyrimidines were synthesized via a one-pot reaction.•Antiproliferative activity of these compounds was evaluated.•Two compounds displayed much stronger antitumor activity than Fluorouracil.•Compound 28 displayed a significant effect on G2/M cell-cycle arrest in MDA-MB-231.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>25016234</pmid><doi>10.1016/j.ejmech.2014.07.017</doi><tpages>8</tpages></addata></record> |
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| subjects | 2,4-Diaminopyrimidines Antineoplastic Agents - chemistry Antineoplastic Agents - isolation & purification Antineoplastic Agents - pharmacology Antiproliferative activity Cell Cycle - drug effects Cell Line, Tumor Cell Proliferation - drug effects Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Hep G2 Cells Humans MCF-7 Cells Molecular Structure One-pot synthesis Piperazine Piperazines - chemistry Piperidine Piperidines - chemistry Pyrimidines - chemical synthesis Pyrimidines - chemistry Pyrimidines - pharmacology Structure-Activity Relationship |
| title | One-pot synthesis and antiproliferative activity of novel 2,4-diaminopyrimidine derivatives bearing piperidine and piperazine moieties |
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