Design, Synthesis, and Biological Evaluation of Novel Thienopyrimidine Derivatives as PI3Kα Inhibitors
Three series of novel thienopyrimidine derivatives <b>9a</b>−<b>l</b>, <b>15a</b>−<b>l</b>, and <b>18a</b>−<b>h</b> were designed and synthesized, and their IC<sub>50</sub> values agains...
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| Format: | Article |
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MDPI AG
2019-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/19/3422 |
| _version_ | 1811223547055439872 |
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| author | Lide Yu Qinqin Wang Caolin Wang Binliang Zhang Zunhua Yang Yuanying Fang Wufu Zhu Pengwu Zheng |
| author_facet | Lide Yu Qinqin Wang Caolin Wang Binliang Zhang Zunhua Yang Yuanying Fang Wufu Zhu Pengwu Zheng |
| author_sort | Lide Yu |
| collection | DOAJ |
| description | Three series of novel thienopyrimidine derivatives <b>9a</b>−<b>l</b>, <b>15a</b>−<b>l</b>, and <b>18a</b>−<b>h</b> were designed and synthesized, and their IC<sub>50</sub> values against four cancer cell lines HepG-2, A549, PC-3, and MCF-7 were evaluated. Most compounds show moderate cytotoxicity against the tested cancer cell lines. The most promising compound <b>9a</b> showed moderate activity with IC<sub>50</sub> values of 12.32 ± 0.96, 11.30 ± 1.19, 14.69 ± 1.32, and 9.80 ± 0.93 µM, respectively. The inhibitory activities of compounds <b>9a</b> and <b>15a</b> against PI3Kα and mTOR kinase were further evaluated. Compound <b>9a</b> exhibited PI3Kα kinase inhibitory activity with IC<sub>50</sub> of 9.47 ± 0.63 µM. In addition, docking studies of compounds <b>9a</b> and <b>15a</b> were also investigated. |
| first_indexed | 2024-04-12T08:34:28Z |
| format | Article |
| id | doaj.art-cd9a5b279d8547d7ba87fbbd38d36a8e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-12T08:34:28Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-cd9a5b279d8547d7ba87fbbd38d36a8e2022-12-22T03:40:03ZengMDPI AGMolecules1420-30492019-09-012419342210.3390/molecules24193422molecules24193422Design, Synthesis, and Biological Evaluation of Novel Thienopyrimidine Derivatives as PI3Kα InhibitorsLide Yu0Qinqin Wang1Caolin Wang2Binliang Zhang3Zunhua Yang4Yuanying Fang5Wufu Zhu6Pengwu Zheng7Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, Nanchang 330013, ChinaJiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, Nanchang 330013, ChinaJiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, Nanchang 330013, ChinaJiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, Nanchang 330013, ChinaCollege of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, ChinaCollege of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, ChinaJiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, Nanchang 330013, ChinaJiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, Nanchang 330013, ChinaThree series of novel thienopyrimidine derivatives <b>9a</b>−<b>l</b>, <b>15a</b>−<b>l</b>, and <b>18a</b>−<b>h</b> were designed and synthesized, and their IC<sub>50</sub> values against four cancer cell lines HepG-2, A549, PC-3, and MCF-7 were evaluated. Most compounds show moderate cytotoxicity against the tested cancer cell lines. The most promising compound <b>9a</b> showed moderate activity with IC<sub>50</sub> values of 12.32 ± 0.96, 11.30 ± 1.19, 14.69 ± 1.32, and 9.80 ± 0.93 µM, respectively. The inhibitory activities of compounds <b>9a</b> and <b>15a</b> against PI3Kα and mTOR kinase were further evaluated. Compound <b>9a</b> exhibited PI3Kα kinase inhibitory activity with IC<sub>50</sub> of 9.47 ± 0.63 µM. In addition, docking studies of compounds <b>9a</b> and <b>15a</b> were also investigated.https://www.mdpi.com/1420-3049/24/19/3422ThienopyrimidinePyrazolePI3Kα inhibitor |
| spellingShingle | Lide Yu Qinqin Wang Caolin Wang Binliang Zhang Zunhua Yang Yuanying Fang Wufu Zhu Pengwu Zheng Design, Synthesis, and Biological Evaluation of Novel Thienopyrimidine Derivatives as PI3Kα Inhibitors Molecules Thienopyrimidine Pyrazole PI3Kα inhibitor |
| title | Design, Synthesis, and Biological Evaluation of Novel Thienopyrimidine Derivatives as PI3Kα Inhibitors |
| title_full | Design, Synthesis, and Biological Evaluation of Novel Thienopyrimidine Derivatives as PI3Kα Inhibitors |
| title_fullStr | Design, Synthesis, and Biological Evaluation of Novel Thienopyrimidine Derivatives as PI3Kα Inhibitors |
| title_full_unstemmed | Design, Synthesis, and Biological Evaluation of Novel Thienopyrimidine Derivatives as PI3Kα Inhibitors |
| title_short | Design, Synthesis, and Biological Evaluation of Novel Thienopyrimidine Derivatives as PI3Kα Inhibitors |
| title_sort | design synthesis and biological evaluation of novel thienopyrimidine derivatives as pi3kα inhibitors |
| topic | Thienopyrimidine Pyrazole PI3Kα inhibitor |
| url | https://www.mdpi.com/1420-3049/24/19/3422 |
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