CHATPRIVACYDONATELOGINREGISTER
DMT-Nexus
FAQWIKIHEALTH & SAFETYARTATTITUDEACTIVE TOPICS
Marine indole alkaloids: potential new drug leads Options
 
entheogenic-gnosis
#1 Posted : 11/27/2016 11:47:41 PM
DMT-Nexus member


Posts: 2889
Joined: 31-Oct-2014
Last visit: 03-Nov-2018
The article "Marine indole alkaloids: potential new drug leads for the control of depression and anxiety by Anna J. Kochanowska-Karamyan and Mark T. Hamann" discusses 5-bromo-N,N-DMT and 5,6-dibromo-DMT (amoung other marine indoles) as potential medications in relation to their serotonin receptor site agonism...

The full article is available in the link.
https://www.ncbi.nlm.nih...mc/articles/PMC2922063/
Quote:

Marine monoindole alkaloids, sharing structure similarities with serotonin, are certain to become useful tools to facilitate the understanding of serotonin receptor function and generate new drug leads for the treatment of depression, anxiety, migraines and other 5HT receptor related disorders https://www.ncbi.nlm.nih...mc/articles/PMC2922063/


Quote:
The structural similarity of indole alkaloids to endogenous amines and neurotransmitters has led researchers to postulate the possible neurological activity of these molecules. Several compounds carrying an indole moiety have been reported to possess affinity towards different serotonin receptors: barettin, 8,9-dihydrobarettin,13 tris-indole alkaloids gelliusine A and B,14 and σ-conotoxin.15 Methylaplysinopsin (1) (Fig. 2) isolated from Aplysinopsis reticulata by Baird-Lambert et al. was reported to inhibit monoamine oxidase (MAO) and to displace serotonin from its receptors.16 Other molecules from this group: 6-bromo-2′-de-N-methylaplysinopsin (2), 6-bromoaplysinopsin (3), and N-3′-ethylaplysinopsin (4) (Fig. 2) isolated from Smenospongia aurea were reported to displace high-affinity antagonist binding for human 5-HT2C and 5-HT2A receptors.17 N-3′-ethylaplysinopsin did not display selectivity to either of these two receptors (Ki of 3.5 μM and 1.7 μM for 5HT2C and 5HT2A receptor, respectively). 6-Bromoaplysinopsin showed only low selectivity towards 5HT2C receptors (Ki 0.33 μM and 2.0 μM for 5HT2C and 5HT2A receptor, respectively); however 6-bromo-2′-de-N-methylaplysinopsin exhibited strong (40 fold) selectivity to 5HT2C receptors (Ki 2.3 μM for 5HT2C and >100 μM for 5HT2A). Besides neurological activity, 6-bromoaplysinopsin also showed significant activity against Plasmodium falciparum.

5,6-dibromo-N,N-dimethyltryptamine (5)18 and 5-bromo-N,N-dimethyltryptamine (6)19 (Fig. 3) exhibited antimicrobial activity as reported by Tymiak.20 The dibrominated compound was significantly more active over the monobromotryptamine. Both of the compounds were also found to possess neurological activity: 5,6-dibromo-N,N-dimethyltryptamine showed antidepressant action in forced swim test and tail suspension test;21,22 5-bromo-N,N-dimethyltryptamine exhibited strong sedative effect in the locomotor activity test https://www.ncbi.nlm.nih...mc/articles/PMC2922063/


-eg
 

Trippy glass for trippy people.
 
entheogenic-gnosis
#2 Posted : 11/27/2016 11:55:13 PM
DMT-Nexus member


Posts: 2889
Joined: 31-Oct-2014
Last visit: 03-Nov-2018
The pharmocological properties of 6-bromo-2′-de-N-methylaplysinopsin and related compounds particularly interest me ...

http://www.ncbi.nlm.nih....mc/articles/PMC2946983/

Quote:
Abstract
In addition to the sesquiterpene-phenol aureols (1), 6'-chloroaureol (2), and aureol acetate (3), eight indole alkaloids including the new N-3'-ethylaplysinopsin (9) have been isolated from the Jamaican sponge Smenospongia aurea. Makaluvamine O (10), a new member of the pyrroloiminoquinone class, was also isolated. The structures were characterized by spectroscopic methods, and two new derivatives of aureol were prepared to optimize the biological activity. Aureol N,N-dimethyl thiocarbamate (1a) and 6-bromoaplysinopsin (7) exhibit significant antimalarial and antimycobacterial activity in vitro. Compound 6 showed activity against the Plasmodium enzyme plasmepsin II. The 6-bromo-2'-de-N-methylaplysinopsin (6), 6-bromoaplysinopsin (7), and N-3'-ethylaplysinopsin (9) displaced high-affinity [(3)H]antagonist ligands from cloned human serotonin 5-HT(2) receptor subtypes, whereas the other compounds tested did not. Remarkably, the 6-bromo-2'-de-N-methylaplysinopsin (6) showed a > 40-fold selectivity for the 5-HT(2C) subtype over the 5-HT(2A) subtype.
https://www.researchgate...nge_Smenospongia_a_urea


-eg
 
exquisitus
#3 Posted : 11/28/2016 1:37:21 AM
DMT-Nexus member


Posts: 191
Joined: 30-Jul-2012
Last visit: 24-Aug-2020
interesting. thanx for posting
 
entheogenic-gnosis
#4 Posted : 11/29/2016 3:15:17 PM
DMT-Nexus member


Posts: 2889
Joined: 31-Oct-2014
Last visit: 03-Nov-2018
I'm surprised that more people are not as enthusiastic as myself regarding the potential of these marine derived indole and tryptamine compounds....


https://www.ncbi.nlm.nih...2922063/?report=classic
According to the World Health Organization, major depression will become the second leading cause of death by the year 2020 due to the complications arising from cardiovascular system and stress.61 There is a tremendous unmet need for new, safer and more effective antidepressant drugs since currently used antidepressants have significant side effects and about 30% of the population does not respond to these current treatments.62 Marine natural products have been overlooked as potent neurologically active molecules, considered primarily as anticancer and antimicrobial leads.

Marine indole alkaloids represent a rich group of natural compounds and have tremendous potential to become new drug leads for various psychiatric disorders as well as to provide better insights into the understanding of serotonin receptor function. These molecules are reasonable synthetic targets which further enhances their value as possible drug leads, however few if any have been prepared as part of synthetic or medicinal chemistry studies designed to generate optimized leads for depression and anxiety.




Misc. Fun from the article:
https://www.ncbi.nlm.nih...2922063/?report=classic
Research completed by Blair and co-workers43 on thieno[3,2-b]- and thieno[2,3-b] pyrrole bioisosters of N,N-dimethyltryptamine revealed that thiophene cannot serve as a replacement for the phenyl ring in the indole moiety of tryptamines which bind to 5HT2 receptors. However, thiophene can be a suitable bioisostere for compounds possessing activity to 5HT1A receptor. Another paper by Blair et al. reports the effect of ring fluorination on the activity of hallucinogenic tryptamines.44 According to their findings, fluorination of tryptamines in positions 4, 5, 6, and 7 reduces hallucinogenic activity. Introducing fluorine at the 6 position of 5-methoxy-N,N-dimethyltryptamine decreases the 5HT1A receptor binding affinity. For example, compound 73 exhibited a Ki of 84.5 nM, while compound 70 exhibited a Ki of 1.7 nM. In the case of N,N-dimethyltryptamine, fluorination at position 6 caused a 5 fold decrease in affinity towards the 5HT1A receptor (compound 69 versus 75).

Fluorination of 5-methoxy-N,N-dimethyltryptamine at position 4 led to increased affinity towards the 5-HT1A receptor and resulted in potent and selective 4-fluoro-5-methoxy-N,N-dimethyltryptamine (74) with a Ki of 0.23 nM (compared to a Ki of 1.7 nM for compound 70). In the case of 5HT2A and 5HT2C receptors, fluorination at position 6 has only insignificant effects on the affinity to these receptors. Chen et al. described the process of preparation of N-(2-arylethyl)benzamines (compounds 76-82) as antagonists of 5HT6 receptors.45 Authors disclosed the use of these antagonists to treat cognitive dysfunction and any disorders associated with 5HT6 receptors: age-related cognitive disorders, anxiety, schizophrenia, Parkinson's disease, epilepsy, convulsions, migraine, and sleep disorders.

In 1998, Audia et al. presented several 8-substituted tetrahydro-beta-carboline compounds and tryptamine-like intermediates possessing high affinity towards all the subtypes of 5HT2 receptors.46 Compounds 83-89 were prepared to serve as molecular tools to develop selective therapeutic 5HT2A and 5HT2C agents, as well as to become effective drugs by themselves. Another patent publication by Audia et al. describes compounds 90-104 with affinity towards 5HT2A, 5HT2B and 5HT2C which could be useful in the treatment of various disorders associated with these receptors, including tachygastria, ichlasia, dyspepsia, schizophrenia, anxiety, depression and migraines.47 Indole derivatives 105, 106 and 107 and their affinity to 5HT2 receptors were the subject of a patent published in 1995 by Audia et al.48 This publication claimed the use of the aforementioned compounds to protect or to treat mammals suffering from 5HT2 receptor related disorders such as hypertension, depression and anxiety. Compounds 108, 109, 110, 112 and 113 were disclosed as inhibitors of angiogenesis, which plays a crucial role in the pathogenesis of cancer, immune and inflammatory disorders.49

Another subtype of serotonin receptors, 5-HT7, has been recently linked to psychiatric disorders like depression and schizophrenia, but their function still remains largely unknown. Vermeulen et al. presented a comprehensive study of inverse agonists of these receptors and determined that tryptamine derivatives like compound 111 without additional aromatic rings exhibit only poor affinity towards these receptors.50

A series of enantiomeric pairs of α-methyltryptamines was investigated by Nichols et al.51 The authors tested tryptamine analogues in 5HT1B and 5HT2 receptor binding assays and showed that enantioselectivity at both binding sites varied depending on the aromatic substituents. At both receptor subtypes, the order of affinity for the α-methyltryptamines was 5-substituted (116) > 4-substituted (115) > unsubstituted (114) > 6-substituted (117). In the case of 5-hydroxy-α-methyltryptamine (119) an S isomer had higher affinity to both receptors over the R isomer. For compounds 115 and 118, the R isomers exhibited higher affinity at the 5HT1B receptor but not at the 5HT2.



-eg
entheogenic-gnosis attached the following image(s):
nihms195524f10.jpg (51kb) downloaded 99 time(s).
nihms195524f3a.jpg (25kb) downloaded 96 time(s).
nihms195524f2.jpg (36kb) downloaded 94 time(s).
 
endlessness
#5 Posted : 11/29/2016 4:34:37 PM

DMT-Nexus member

Moderator

Posts: 13899
Joined: 19-Feb-2008
Last visit: 17-Jun-2021
Location: Jungle
Yes it's definitely very interesting.. We have an older thread about it, has some good discussion and info with sources:

https://www.dmt-nexus.me...aspx?g=posts&t=24054
 
entheogenic-gnosis
#6 Posted : 12/1/2016 1:43:57 PM
DMT-Nexus member


Posts: 2889
Joined: 31-Oct-2014
Last visit: 03-Nov-2018
endlessness wrote:
Yes it's definitely very interesting.. We have an older thread about it, has some good discussion and info with sources:

https://www.dmt-nexus.me...spx?g=posts&t=24054



Thank you for the link, I often overlook or fail to locate older threads which relate to a topic which I'm currently researching.

I'm never sure if it's appropriate to post in these older threads, or once I have started a thread, and then found an older thread already existed, I'm never sure what the proper etiquette is, to add to the existing thread or continue with my own.

Thanks again,

-eg
 
entheogenic-gnosis
#7 Posted : 12/1/2016 1:45:09 PM
DMT-Nexus member


Posts: 2889
Joined: 31-Oct-2014
Last visit: 03-Nov-2018
More related research:

Quote:
Cytotoxic bromoindole derivatives and terpenes from the Philippine marine sponge Smenospongia sp.
Tasdemir D1, Bugni TS, Mangalindan GC, Concepción GP, Harper MK, Ireland CM.
Author information
Abstract
A detailed chemical analysis of a Philippine marine sponge Smenospongia sp. has been performed. This study yielded four new metabolites, 5-bromo-L-tryptophan (1), 5-bromoabrine (2), 5,6-dibromoabrine (3) and 5-bromoindole-3-acetic acid (4). The pyrroloiminoquinone alkaloid, makaluvamine O (5) as well as 5,6-dibromotryptamine (6), aureol (7) and furospinulosin 1 (Cool were also isolated. Although 1 and 4 have been synthesized previously, this is the first report on the isolation of these compounds from a natural source. The furanosesterterpene furospinulosin 1 (Cool was obtained for the first time from the genus Smenospongia. The structures of all compounds were established by spectroscopic methods (UV, IR, 1D and 2D NMR, MS, [alpha]D). The cytotoxic potential of 1-8 was evaluated in a panel of isogenic HCT-116 human colon tumor cell lines.
https://www.ncbi.nlm.nih.gov/pubmed/12440734
 
DreaMTripper
#8 Posted : 12/2/2016 12:59:45 AM

DMT-Nexus member


Posts: 1887
Joined: 18-Jan-2008
Last visit: 01-Apr-2021
Thats cool man will have to dig out the research I was keeping an eye on, complicated stuff.
 
Mitakuye Oyasin
#9 Posted : 12/2/2016 2:09:06 AM

DMT-Nexus member


Posts: 815
Joined: 10-Dec-2010
Last visit: 18-Jun-2021
Location: Earth's atmosphere
The most recent Hamilton's Pharmacopia did an episode on this entitled Fish N Trips. It was interesting, but I wish they would have gotten into the chemistry a lot more.
Let us declare nature to be legitimate. All plants should be declared legal, and all animals for that matter. The notion of illegal plants and animals is obnoxious and ridiculous.
— Terence McKenna


All my posts are hypothetical and for educational/entertainment purposes, and are not an endorsement of said activities. SWIM (a fictional character based on other people) either obtained a license for said activity, did said activity where it is legal to do so, or as in most cases the activity is completely fictional.
 
entheogenic-gnosis
#10 Posted : 12/2/2016 1:48:59 PM
DMT-Nexus member


Posts: 2889
Joined: 31-Oct-2014
Last visit: 03-Nov-2018
Mitakuye Oyasin wrote:
The most recent Hamilton's Pharmacopia did an episode on this entitled Fish N Trips. It was interesting, but I wish they would have gotten into the chemistry a lot more.


Yeah, I started a thread when Hamilton's series aired, I've been keeping track of it as it has progressed, though out of being redundant I'll reserve my comments on the matter for that thread...

...however, I did find it fascinating that in that episode the collected Smenospongia sponge stained the water in the collection vessel a purple/blue color...possibly a relation to the indole alkaloids present?

...I also found the human report from that episode regarding 5-br-DMT fascinating.

-eg

 
entheogenic-gnosis
#11 Posted : 12/2/2016 2:22:19 PM
DMT-Nexus member


Posts: 2889
Joined: 31-Oct-2014
Last visit: 03-Nov-2018
In an unrelated thread dreamer directed me to this link:

http://www.vice.com/read...dmt-000481-v20n3/page/0
Sea DMT - Jason wallach and Hamilton Morris (via vice)


It appears the purple staining of the water is of interest:
Quote:
I am very much interested in the possibility that these dark pigments result from the dimerization of bromoindoles into tyrian-purple type pigments. I have personally seen a dram vile containing a small quantity of methanolic Smenospongia extract, and true to the reports, the color was a deep violet tending toward black. Additionally, any experienced tryptamine chemist will testify that synthetic intermediates (particularly crude acid chlorides) quite literally come in all the colors of the rainbow.
http://www.vice.com/read...dmt-000481-v20n3/page/0


Also in the same link I found a letter published by Jason wallach and Hamilton Morris regarding human consumption of 5-br-DMT, which at oral dose was speculated to have antidepressant activity just as the currant research suggests, even more fascinating was the psychoactivity of the compound. (Pictures attached)

-eg

entheogenic-gnosis attached the following image(s):
f855767aa7a99a6cf7461c601b01ab83.jpg (176kb) downloaded 21 time(s).
8fb8a012f0f6604b5641d7a76dcb512f.jpg (227kb) downloaded 21 time(s).
c3d0058d523813933f1d993df6795bae.jpg (187kb) downloaded 21 time(s).
 
 
Users browsing this forum
Guest

DMT-Nexus theme created by The Traveler
This page was generated in 0.039 seconds.