Lee, Fong-Kai and Chan, Nathaniel Jia-Yoong and Krishnan, Premanand and Salam, Dayang Sharyati Datu Abdul and Chee, Xavier Wezen and Muhamad, Azira and Low, Yun Yee and Ting, Kang-Nee and Lim, Kuan-Hon (2024) Preparation and Preliminary Structure-Activity Relationship Studies of Schwarzinicine A Analogs as Vasorelaxant Agents. Journal of Natural Products, 87 (4). pp. 675-691. ISSN 0163-3864, DOI https://doi.org/10.1021/acs.jnatprod.3c00707.
Full text not available from this repository.Abstract
Schwarzinicines A-D, a series of alkaloids recently discovered from Ficus schwarzii, exhibit pronounced vasorelaxant activity in rat isolated aorta. Building on this finding, a concise synthesis of schwarzinicines A and B has been reported, allowing further investigations into their biological properties. Herein, a preliminary exploration of the chemical space surrounding the structure of schwarzinicine A (1) was carried out aiming to identify structural features that are essential for vasorelaxant activity. A total of 57 analogs were synthesized and tested for vasorelaxant activity in rat isolated aorta. Both efficacy (E-max) and potency (EC50) of these analogs were compared. In addition to identifying structural features that are required for activity or associated with potency enhancement effect, four analogs showed significant potency improvements of up to 40.2-fold when compared to 1. Molecular dynamics simulation of a tetrameric 44-bound transient receptor potential canonical-6 (TRPC6) protein indicated that 44 could potentially form important interactions with the residues Glu509, Asp530, Lys748, Arg758, and Tyr521. These results may serve as a foundation for guiding further structural optimization of the schwarzinicine A scaffold, aiming to discover even more potent analogs.
| Item Type: | Article |
|---|---|
| Funders: | Malaysia Toray Science Foundation (FRGS/1/2020/STG04/UNIM/02/3); (FRGS/1/2017/SKK10/UNIM/01/1), MOHE Malaysia (TML-CA/17.195(17/G62)), Malaysia Toray Science Foundation |
| Uncontrolled Keywords: | Protein-Structure |
| Subjects: | Q Science > QD Chemistry R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica |
| Divisions: | Faculty of Science > Department of Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 22 Oct 2024 07:45 |
| Last Modified: | 22 Oct 2024 07:45 |
| URI: | http://eprints.um.edu.my/id/eprint/45483 |
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