Discovery and Structure-Based Optimization of  6-Bromotryptamine Derivatives as Potential 5-HT2A Receptor Antagonists

Ding, Lijian; He, Shan; Wu, Wei; Jin, Haixiao; Zhu, Peng; Zhang, Jinrong; Wang, Tingting; Yuan, Ye; Yan, Xiaojun

doi:10.3390/molecules200917675

Submit to this Journal Review for this Journal Edit a Special Issue

Article Menu

...

Open AccessArticle

Discovery and Structure-Based Optimization of 6-Bromotryptamine Derivatives as Potential 5-HT_2A Receptor Antagonists

^1,2,

^1,3,*

⁴,

¹,

⁴,

¹,

¹,

¹ and

^4,*

Laboratory of Marine Natural Products, School of Marine Sciences, Ningbo University, Ningbo 315211, China

College of Pharmacy, Jinan University, Guangzhou 510632, China

Collaborative Innovation Center for Zhejiang Marine High-efficiency and Healthy Aquaculture, Ningbo 315211, China

⁴

Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo 315211, China

Authors to whom correspondence should be addressed.

Academic Editor: Thomas J. Schmidt

Molecules 2015, 20(9), 17675-17683; https://doi.org/10.3390/molecules200917675

Received: 23 August 2015 / Revised: 17 September 2015 / Accepted: 21 September 2015 / Published: 23 September 2015

(This article belongs to the Section Natural Products Chemistry)

View Full-Text Download PDF

Browse Figures

Citation Export

Abstract

5-Hydroxytryptamine type 2A (5-HT_2A) receptor is an important target for developing innovative antipsychotic agents in neuropsychiatric disorder therapies. To search for 5-HT_2A receptor antagonists, a new indole alkaloid termed 6-bromo-N-propionyltryptamine (1), together with one known homologue 6-bromo-N-acetyltryptamine (2) were isolated and identified from a marine bacterium Pseudoalteromonas rubra QD1-2. Compound 1 with an N-propionyl side chain exhibited stronger 5-HT_2A receptor antagonist activity than that of N-acetyl derivative (2), indicating that 6-bromotryptamine analogues with a longer chain acyl group perhaps displayed a more potent capacity to the target. Therefore, a series of new 6-bromotryptamine analogues (3–7) with different chain length of the acyl group (C4–C8) were prepared and evaluated activity against 5-HT_2A receptor. Remarkably, 6-bromo-N-hexanoyltryptamine (5) displayed the most effective inhibitory activity, which was 5-fold stronger than that of the parent compound 1 and showed 70% efficacy of the positive control (ketanserin tartrate). View Full-Text

Keywords: 6-bromotryptamine; Pseudoalteromonas rubra; 5-HT_2A receptor; antagonist

▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Share and Cite

MDPI and ACS Style

Ding, L.; He, S.; Wu, W.; Jin, H.; Zhu, P.; Zhang, J.; Wang, T.; Yuan, Y.; Yan, X. Discovery and Structure-Based Optimization of 6-Bromotryptamine Derivatives as Potential 5-HT_2A Receptor Antagonists. Molecules 2015, 20, 17675-17683. https://doi.org/10.3390/molecules200917675

AMA Style

Ding L, He S, Wu W, Jin H, Zhu P, Zhang J, Wang T, Yuan Y, Yan X. Discovery and Structure-Based Optimization of 6-Bromotryptamine Derivatives as Potential 5-HT_2A Receptor Antagonists. Molecules. 2015; 20(9):17675-17683. https://doi.org/10.3390/molecules200917675

Chicago/Turabian Style

Ding, Lijian, Shan He, Wei Wu, Haixiao Jin, Peng Zhu, Jinrong Zhang, Tingting Wang, Ye Yuan, and Xiaojun Yan. 2015. "Discovery and Structure-Based Optimization of 6-Bromotryptamine Derivatives as Potential 5-HT_2A Receptor Antagonists" Molecules 20, no. 9: 17675-17683. https://doi.org/10.3390/molecules200917675

Find Other Styles

Article Metrics

Abstract views Pdf views Html views

Article Access Map by Country/Region

Only visits after 24 November 2015 are recorded.

Article Menu

Discovery and Structure-Based Optimization of 6-Bromotryptamine Derivatives as Potential 5-HT_2A Receptor Antagonists

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI