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TRP Modulators Based on Glycine and Mono-, Bicyclic Terpenoids – Synthesis and Pharmacological Properties
* ,
1  Department of Organic and Pharmaceutical Technologies, Odessa National Polytechnic University
2  Department of Pharmaceutical Chemistry, I.I. Mechnikov Odessa National University

Published: 01 November 2016 by MDPI in 2nd International Electronic Conference on Medicinal Chemistry session ECMC-2

Currently, significant interest in drug development is focused on obtaining drugs that simultaneously affect various pharmacological targets and thus exhibiting combined actions. Herein we demonstrate the possibility of development of novel drugs that are able to simultaneously modulate TRP-channels and bind to glycine receptors. For this purpose esters based on mono- and bicyclic terpenoids (menthol, thymol, carvacrol, guaiacol, eugenol, borneol) and an inhibitory amino acid (glycine) were synthesized via Steglich esterification. Their anticonvulsant action was evaluated by a PTZ-induced convulsion model and analgesic effect − by pharmacological models of thermal and chemical stimuli. All studied esters were found to produce antinociceptive effects and attenuate acute pain more than the reference drug benzocaine after topical application. The present findings indicate that glycine esters of abovementioned terpenoids are not classical prodrugs and possess their own pharmacological activity. Prolonged antiseizure action of the esters was revealed at 24 h after oral administration. Moreover, orally co-administered gidazepam (1 mg/kg) and glycine esters produce synergistic seizure prevention effects.

Keywords: TRP channels, terpenoids, terpene, glycine, anticonvulsant activity
Comments on this paper
George Sladkovsky
Very insightful presentation
Interesting approach and the topic is very up-to-date. The most interesting part is the idea of combining the residual terpenes and inhibitory amino acids in one molecule.

Sergiy Lozovsky
A novel approach
Very promising idea. Keep up the good work.

Alex Lypovets
Appealing piece of work
Data obtained in the study of co-administration of synthetic esters with benzodiazepines is promising. This approach provides information about the possible binding sites of terpenoids and their esters.

Dorothy Smith
I like your idea...
I like your idea and demonstration of the possibilities of new drug development... Nice work!

Natalie Lozitsky
Very interesting research
The idea of possibilities of development of new drugs is very appealing. Nice work!

Vernon Nellis
Interesting study
The choice of Terpenoidesters were interesting and may have formed a better Robison Ester with the (PO4) than Benzocaine for reversible phosphorylation of (TRPV) proteins. Great ideas!

Horst Brandauer
Very interesting resurge
It is a verrry interest results of Your resurge and I will gratulate You for this positive effects..
I hope this used methods are basicly usable to finde in future direction more positive
results as you have find it. My gratulation to You Horst!

Aras Najmaddin
So Nice and Attractive
First of all I would like to congratulate u for getting ur published article, and I would greatly appreciate you to select a very important and attractive issue in the field of organic synthesis, and also for the nice conducting.