Synthesis and Antitumor Activity of a Series of Novel 1-Oxa-4-azaspiro[4,5]deca-6,9-diene-3,8-dione Derivatives
A series of novel 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-diones were designed and synthesized by using 4-aminophenol and α-glycolic acid or lactic acid as starting materials in three or four steps. The key step is the metal-catalyzed oxidative cyclization of the amide to 1-oxa-4-azaspiro[...
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MDPI AG
2019-03-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/24/5/936 |
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| author | Ze Yang Qiu Zhong Shilong Zheng Guangdi Wang Ling He |
| author_facet | Ze Yang Qiu Zhong Shilong Zheng Guangdi Wang Ling He |
| author_sort | Ze Yang |
| collection | DOAJ |
| description | A series of novel 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-diones were designed and synthesized by using 4-aminophenol and α-glycolic acid or lactic acid as starting materials in three or four steps. The key step is the metal-catalyzed oxidative cyclization of the amide to 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-diones (10a and 10b), the reaction conditions of which are investigated and optimized. The anticancer activity of 17 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-dione derivatives was evaluated. Preliminary results showed that 15 compounds have moderate to potent activity against human lung cancer A549, human breast cancer MDA-MB-231, and human cervical cancer HeLa cancer cell lines. Among them, compounds 11b and 11h were the most potent against A549 cell line with 0.18 and 0.19 µM of IC50, respectively; compounds 11d, 11h, and 11k showed the most potent cytotoxicity against MDA-MB-231 cell line with 0.08, 0.08, and 0.09 µM of IC50, respectively, while the activities of 11h, 11k, and 12c against HeLa cell line were the most potent with 0.15, 0.14, and 0.14 µM of IC50, respectively. Compound 11h is a promising candidate for further development, which emerged as the most effective compound overall against the three tested cancer cell lines. |
| first_indexed | 2024-04-13T02:52:20Z |
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| id | doaj.art-77ae821f0d204691b2051fce90bd2cbb |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T02:52:20Z |
| publishDate | 2019-03-01 |
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| series | Molecules |
| spelling | doaj.art-77ae821f0d204691b2051fce90bd2cbb2022-12-22T03:05:49ZengMDPI AGMolecules1420-30492019-03-0124593610.3390/molecules24050936molecules24050936Synthesis and Antitumor Activity of a Series of Novel 1-Oxa-4-azaspiro[4,5]deca-6,9-diene-3,8-dione DerivativesZe Yang0Qiu Zhong1Shilong Zheng2Guangdi Wang3Ling He4Key Laboratory of Drug–Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, Sichuan, ChinaDepartment of Chemistry, RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USADepartment of Chemistry, RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USADepartment of Chemistry, RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USAKey Laboratory of Drug–Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, Sichuan, ChinaA series of novel 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-diones were designed and synthesized by using 4-aminophenol and α-glycolic acid or lactic acid as starting materials in three or four steps. The key step is the metal-catalyzed oxidative cyclization of the amide to 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-diones (10a and 10b), the reaction conditions of which are investigated and optimized. The anticancer activity of 17 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-dione derivatives was evaluated. Preliminary results showed that 15 compounds have moderate to potent activity against human lung cancer A549, human breast cancer MDA-MB-231, and human cervical cancer HeLa cancer cell lines. Among them, compounds 11b and 11h were the most potent against A549 cell line with 0.18 and 0.19 µM of IC50, respectively; compounds 11d, 11h, and 11k showed the most potent cytotoxicity against MDA-MB-231 cell line with 0.08, 0.08, and 0.09 µM of IC50, respectively, while the activities of 11h, 11k, and 12c against HeLa cell line were the most potent with 0.15, 0.14, and 0.14 µM of IC50, respectively. Compound 11h is a promising candidate for further development, which emerged as the most effective compound overall against the three tested cancer cell lines.http://www.mdpi.com/1420-3049/24/5/9361-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-dioneintramolecular oxidationantitumor activity |
| spellingShingle | Ze Yang Qiu Zhong Shilong Zheng Guangdi Wang Ling He Synthesis and Antitumor Activity of a Series of Novel 1-Oxa-4-azaspiro[4,5]deca-6,9-diene-3,8-dione Derivatives Molecules 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-dione intramolecular oxidation antitumor activity |
| title | Synthesis and Antitumor Activity of a Series of Novel 1-Oxa-4-azaspiro[4,5]deca-6,9-diene-3,8-dione Derivatives |
| title_full | Synthesis and Antitumor Activity of a Series of Novel 1-Oxa-4-azaspiro[4,5]deca-6,9-diene-3,8-dione Derivatives |
| title_fullStr | Synthesis and Antitumor Activity of a Series of Novel 1-Oxa-4-azaspiro[4,5]deca-6,9-diene-3,8-dione Derivatives |
| title_full_unstemmed | Synthesis and Antitumor Activity of a Series of Novel 1-Oxa-4-azaspiro[4,5]deca-6,9-diene-3,8-dione Derivatives |
| title_short | Synthesis and Antitumor Activity of a Series of Novel 1-Oxa-4-azaspiro[4,5]deca-6,9-diene-3,8-dione Derivatives |
| title_sort | synthesis and antitumor activity of a series of novel 1 oxa 4 azaspiro 4 5 deca 6 9 diene 3 8 dione derivatives |
| topic | 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-dione intramolecular oxidation antitumor activity |
| url | http://www.mdpi.com/1420-3049/24/5/936 |
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