A Structure–Activity Relationship Study of Trypargine and Opacaline β-Carbolines
Abstract
The marine environment represents a rich source of novel antimicrobial compounds. This study investigated the isolation and synthesis of antimicrobial agents from the New Zealand ascidian Pseudodistoma opacum to identify natural products and derivatives with potential pharmacological applications. Screening of a marine natural product library and related synthetic analogues revealed several compounds exhibiting antibiotic-potentiating activity in combination with doxycycline against Pseudomonas aeruginosa. To further explore these findings, the most active natural product, opacaline A (1), was synthesized, and a structure–activity relationship (SAR) study was conducted to identify key structural features required for activity. This work reports the first total synthesis of opacaline A (1) and racemic 7-bromohomotrypargine (3). Biological evaluation demonstrated that the presence of a bromine substituent and a free amine or guanidine group is essential for both intrinsic antimicrobial activity and antibiotic potentiation. Additionally, both oxidation states of the β-carboline ring (aromatic and tetrahydro-) were found to retain activity. These findings provide insight into the structural requirements for activity and support further development of these compounds as antimicrobial adjuvants.
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BibTeX
@article{chen2026structureactivity,
title = {{A Structure–Activity Relationship Study of Trypargine and Opacaline β-Carbolines}},
author = {Dan Chen and Florent Rouvier and Jean Michel Brunel and Brent R Copp and Melissa M Cadelis},
journal = {Marine drugs},
year = {2026},
month = jul,
doi = {10.3390/md24070248},
url = {https://hal.science/hal-05804929v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A Structure–Activity Relationship Study of Trypargine and Opacaline β-Carbolines
AU - Dan Chen
AU - Florent Rouvier
AU - Jean Michel Brunel
AU - Brent R Copp
AU - Melissa M Cadelis
PY - 2026
DA - 2026/07/17
JO - Marine drugs
DO - 10.3390/md24070248
UR - https://hal.science/hal-05804929v1
AB - The marine environment represents a rich source of novel antimicrobial compounds. This study investigated the isolation and synthesis of antimicrobial agents from the New Zealand ascidian Pseudodistoma opacum to identify natural products and derivatives with potential pharmacological applications. Screening of a marine natural product library and related synthetic analogues revealed several compounds exhibiting antibiotic-potentiating activity in combination with doxycycline against Pseudomonas aeruginosa. To further explore these findings, the most active natural product, opacaline A (1), was synthesized, and a structure–activity relationship (SAR) study was conducted to identify key structural features required for activity. This work reports the first total synthesis of opacaline A (1) and racemic 7-bromohomotrypargine (3). Biological evaluation demonstrated that the presence of a bromine substituent and a free amine or guanidine group is essential for both intrinsic antimicrobial activity and antibiotic potentiation. Additionally, both oxidation states of the β-carboline ring (aromatic and tetrahydro-) were found to retain activity. These findings provide insight into the structural requirements for activity and support further development of these compounds as antimicrobial adjuvants.
SN - 1660-3397
SN - 1660-3397
ER -