Analysis of electronic structures of physostigmine analogs
文献类型：期刊论文
| 作者 | Hu, ZJ; Jiang, HL ; Chen, JZ; Chen, KX; Ji, RY
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 1998-07 |
| 卷号 | 19期号:4页码:322-326 |
| 关键词 | cholinesterase inhibitors physostigmine molecular models computer-aided design |
| ISSN号 | 0253-9756 |
| 文献子类 | Article |
| 英文摘要 | AIM: To elucidate the action mechanism and structural prerequisites of 21 physostigmine analogs as acetylcholinesterase inhibitors at the molecular level, and help the rational design of these dihydroindoline inhibitors. METHODS: Initial structures of these compounds were built and minimized by SYBYL 6.2 molecular modeling software, Conformations of those molecules with the highest predictive abilities in the Comparative Molecular Field Analysis model were chosen to the semiempirical quantum chemical calculations. RESULTS: (I) The highest occupied molecular orbital (HOMO) consisted mainly of the orbitals in phenyl group and N-1 atom; the lowest unoccupied molecular orbital (LUMO) of the molecules was contributed from phenyl group and C-11 atom, While the HOMO energies did not show any recognizable relationship with activity, the LUMO energies showed a decreased tendency with increasing activity. The active compounds showed lower LUMO energies, (2) The carbon atom (C-11) had the most positive net atom charge. The most active compound had the most positive charge on this carbon, but had the lower charges on the carbonyl oxygen (O-12) which Tvas the most negative charge atom. (3) The bond order of carbon-oxygen bond (C-11 - O-10) was invariant across the series of the compounds. (4) Compounds with too high or too low total dipole moment had lower activities, while the most active one had a lower molecular polarizability. CONCLUSION: A molecular model was suggested to explain the possible mode of action by which these compounds inhibit acetylcholinesterase. |
| WOS关键词 | BINDING |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000074666500006 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/274820]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Chen, KX |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hu, ZJ,Jiang, HL,Chen, JZ,et al. Analysis of electronic structures of physostigmine analogs[J]. ACTA PHARMACOLOGICA SINICA,1998,19(4):322-326. |
| APA | Hu, ZJ,Jiang, HL,Chen, JZ,Chen, KX,&Ji, RY.(1998).Analysis of electronic structures of physostigmine analogs.ACTA PHARMACOLOGICA SINICA,19(4),322-326. |
| MLA | Hu, ZJ,et al."Analysis of electronic structures of physostigmine analogs".ACTA PHARMACOLOGICA SINICA 19.4(1998):322-326. |
入库方式： OAI收割
来源：上海药物研究所
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