Marine Cyclic Guanidine Alkaloids Monanchomycalin B and Urupocidin A Act as Inhibitors of TRPV1, TRPV2 and TRPV3, but not TRPA1 Receptors.
Marine sponges contain a variety of low-molecular-weight compounds including guanidine alkaloids possessing different biological activities. Monanchomycalin B and urupocidin A were isolated from the marine spongeMonanchora pulchra.We found that they act as inhibitors of the TRPV1, TRPV2, and TRPV3 channels, but are inactive against the TRPA1 receptor. Monanchomycalin B is the most active among all published marine alkaloids (EC506.02, 2.84, and 3.25 μM for TRPV1, TRPV2, and TRPV3, correspondingly). Moreover, monanchomycalin B and urupocidin A are the first samples of marine alkaloids affecting the TRPV2 receptor. Two semi-synthetic urupocidin A derivatives were also obtained and tested against TRP (Transient Receptor Potential) receptors that allowed us to collect some data concerning the structure-activity relationship in this series of compounds. We showed that the removal of one of three side chains or double bonds in the other side chains in urupocidin A led to a decrease of the inhibitory activities. New ligands specific to the TRPV subfamily may be useful for the design of medicines as in the study of TRP channels biology.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia. july@mx.ibch.ru.
Yuliya
Y
Korolkova
G.B. Elyakov Pacific Institute of Bioorganic Chemistry (PIBOC), Russian Academy of Sciences, Prospect 100 let Vladivostoku, 159, Vladivostok 690022, Russia. makarieva@piboc.dvo.ru.
Tatyana
T
Makarieva
G.B. Elyakov Pacific Institute of Bioorganic Chemistry (PIBOC), Russian Academy of Sciences, Prospect 100 let Vladivostoku, 159, Vladivostok 690022, Russia. dark_xen@mail.ru.
Kseniya
K
Tabakmakher
G.B. Elyakov Pacific Institute of Bioorganic Chemistry (PIBOC), Russian Academy of Sciences, Prospect 100 let Vladivostoku, 159, Vladivostok 690022, Russia. shubina@piboc.dvo.ru.
Larisa
L
Shubina
G.B. Elyakov Pacific Institute of Bioorganic Chemistry (PIBOC), Russian Academy of Sciences, Prospect 100 let Vladivostoku, 159, Vladivostok 690022, Russia. catrinog.81@mail.ru.
Ekaterina
E
Kudryashova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia. ay@land.ru.|Sechenov First Moscow State Medical University, Institute of Molecular Medicine, Trubetskaya str.8, bld. 2, Moscow 119991, Russia. ay@land.ru.
Yaroslav
Y
Andreev
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia. mosharova@mail.ru.
Irina
I
Mosharova
Korea Institute of Ocean Science & Technology, Marine Natural Products Laboratory, Ansan 426-744, Korea. hslee@kiost.ac.kr.
Hyi-Seung
HS
Lee
Korea Institute of Ocean Science & Technology, Marine Natural Products Laboratory, Ansan 426-744, Korea. yjlee@kiost.ac.kr.
Yeon-Ju
YJ
Lee
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, Moscow 117997, Russia. serg@ibch.ru.
Sergey
S
Kozlov
D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D059001:Aquatic Organisms / Q000737:chemistry*; D019791:Guanidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D011161:Porifera / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
D000470:Alkaloids; D006146:Guanidines; D050916:TRPV Cation Channels; C000597826:urupocidin A; D019791:Guanidine
Monanchora pulchra; TRPA1; TRPV1; TRPV2; TRPV3; guanidine alkaloids; sponge