Chemical Synthesis, Safety and Efficacy of Antihypertensive Candidate Drug 221s (2,9)
Hypertension is the main risk factor of cardiovascular and cerebrovascular diseases. In this paper, a novel compound known as 221s (2,9), which includes tanshinol, borneol and a mother nucleus of ACEI, was synthesized by condensation esterification, deprotection, amidation, deprotection, and amidati...
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MDPI AG
2023-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/13/4975 |
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| author | Bei Qin Lili Yu Rong Wang Yimei Tang Yunmei Chen Nana Wang Yixin Zhang Xiong Tan Kuan Yang Bo Zhang Maofang He Yuzhen Zhang Yaqi Hu |
| author_facet | Bei Qin Lili Yu Rong Wang Yimei Tang Yunmei Chen Nana Wang Yixin Zhang Xiong Tan Kuan Yang Bo Zhang Maofang He Yuzhen Zhang Yaqi Hu |
| author_sort | Bei Qin |
| collection | DOAJ |
| description | Hypertension is the main risk factor of cardiovascular and cerebrovascular diseases. In this paper, a novel compound known as 221s (2,9), which includes tanshinol, borneol and a mother nucleus of ACEI, was synthesized by condensation esterification, deprotection, amidation, deprotection, and amidation, with borneol as the initial raw material, using the strategy of combinatorial molecular chemistry. The structure of the compound was confirmed by <sup>1</sup>H NMR, <sup>13</sup>C NMR, and high-resolution mass spectrometry, with a purity of more than 99.5%. The compound 221s (2,9) can significantly reduce the systolic and diastolic blood pressure of SHR rats by about 50 mmHg and 35 mmHg after 4 weeks of administration. The antihypertensive effect of 221s (2,9) is equivalent to that of captopril. The use of 221s (2,9) can reduce the content of Ren, Ang II and ACE in the serum of SHR rats, inhibit the RAAS and enhance the vascular endothelial function by upregulating the level of NO. Pathological studies in this area have shown that high dosage of 221s (2,9) can notably protect myocardial fibrosis in rats and reduce the degeneration and necrosis of myocardial fibers, inflammatory cell infiltration, and proliferation of fibrous tissue in the heart of rat. Therefore, the existing work provided a foundation for preclinical research and follow-up clinical research of 221s (2,9) as a new drug. |
| first_indexed | 2024-03-11T01:34:32Z |
| format | Article |
| id | doaj.art-c0fa5bed114143dbaa9d52b8e68cba42 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T01:34:32Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c0fa5bed114143dbaa9d52b8e68cba422023-11-18T17:06:23ZengMDPI AGMolecules1420-30492023-06-012813497510.3390/molecules28134975Chemical Synthesis, Safety and Efficacy of Antihypertensive Candidate Drug 221s (2,9)Bei Qin0Lili Yu1Rong Wang2Yimei Tang3Yunmei Chen4Nana Wang5Yixin Zhang6Xiong Tan7Kuan Yang8Bo Zhang9Maofang He10Yuzhen Zhang11Yaqi Hu12Xi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Medical University, Xi’an 710021, ChinaXi’an Key Laboratory of Multi Synergistic Antihypertensive Innovative Drug Development, Xi’an Medical University, Xi’an 710021, ChinaHypertension is the main risk factor of cardiovascular and cerebrovascular diseases. In this paper, a novel compound known as 221s (2,9), which includes tanshinol, borneol and a mother nucleus of ACEI, was synthesized by condensation esterification, deprotection, amidation, deprotection, and amidation, with borneol as the initial raw material, using the strategy of combinatorial molecular chemistry. The structure of the compound was confirmed by <sup>1</sup>H NMR, <sup>13</sup>C NMR, and high-resolution mass spectrometry, with a purity of more than 99.5%. The compound 221s (2,9) can significantly reduce the systolic and diastolic blood pressure of SHR rats by about 50 mmHg and 35 mmHg after 4 weeks of administration. The antihypertensive effect of 221s (2,9) is equivalent to that of captopril. The use of 221s (2,9) can reduce the content of Ren, Ang II and ACE in the serum of SHR rats, inhibit the RAAS and enhance the vascular endothelial function by upregulating the level of NO. Pathological studies in this area have shown that high dosage of 221s (2,9) can notably protect myocardial fibrosis in rats and reduce the degeneration and necrosis of myocardial fibers, inflammatory cell infiltration, and proliferation of fibrous tissue in the heart of rat. Therefore, the existing work provided a foundation for preclinical research and follow-up clinical research of 221s (2,9) as a new drug.https://www.mdpi.com/1420-3049/28/13/4975ACEItanshinolborneolantihypertensiveRAAS |
| spellingShingle | Bei Qin Lili Yu Rong Wang Yimei Tang Yunmei Chen Nana Wang Yixin Zhang Xiong Tan Kuan Yang Bo Zhang Maofang He Yuzhen Zhang Yaqi Hu Chemical Synthesis, Safety and Efficacy of Antihypertensive Candidate Drug 221s (2,9) Molecules ACEI tanshinol borneol antihypertensive RAAS |
| title | Chemical Synthesis, Safety and Efficacy of Antihypertensive Candidate Drug 221s (2,9) |
| title_full | Chemical Synthesis, Safety and Efficacy of Antihypertensive Candidate Drug 221s (2,9) |
| title_fullStr | Chemical Synthesis, Safety and Efficacy of Antihypertensive Candidate Drug 221s (2,9) |
| title_full_unstemmed | Chemical Synthesis, Safety and Efficacy of Antihypertensive Candidate Drug 221s (2,9) |
| title_short | Chemical Synthesis, Safety and Efficacy of Antihypertensive Candidate Drug 221s (2,9) |
| title_sort | chemical synthesis safety and efficacy of antihypertensive candidate drug 221s 2 9 |
| topic | ACEI tanshinol borneol antihypertensive RAAS |
| url | https://www.mdpi.com/1420-3049/28/13/4975 |
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