Biomedical Chemistry: Research and Methods, 2018, 1(3), e00027
The 40th Anniversary of the Institute of Physiologically Active Compounds of the Russian Academy of Sciences

Effect of the Cycle Size and Spacer Structure in Tacrine and its Cyclopentyl Homologue Conjugates with 5-(4-trifluoromethyl-phenylamino)-1,2,4-thiadiazole on the Spectrum of their Biological Activity

N.V.* Kovaleva, A.N. Proshin, E.V. Rudakova, N.P. Boltneva, I.V.Serkov, G.F. Makhaeva

Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1 Severny proezd, Moscow region, Chernogolovka, 142432 Russia,*e-mail:

Key words: atacrine; 1,2,4-thiadiazoles; acethylcholinesterase; butyrylcholinesterase; antioxidants; Alzheimer’s disease

DOI: 10.18097/BMCRM00027

The whole version of this paper is available in Russian.

The conjugates of tacrine and its cyclopentyl analogue with 5- (4-trifluoromethyl-phenylamino) -1,2,4-thiadiazole, combined with two different spacers, pentylaminopropane and pentylaminopropene, were synthesized. Their esterase profile, the ability to displace propidium from the peripheral anionic site (PAS) of acetylcholinesterase (AChE) and antioxidant activity in the ABTS test were investigated. The compounds obtained effectively inhibit cholinesterases with a predominant effect on butyrylcholinesterase, displace propidium from the PAS of Electrophorus electricus AChE (EeAChE) and exhibit a high radical-scavenging capacity. It is shown that, depending on the spacer structure, particulary, the presence of a propenamine or propanamine fragment, the spectrum of biological activity of the conjugates changes.

Figure 1. Synthesis of the target conjugates 4a,b and 5а,b.

Table 1. Inhibitor activity and selectivity of conjugates 4a (n=1), 4b (n=2), 5a (n=1), 5b (n=2) toward AChE, BChE and CaE.

Table 2. The ability of conjugates 4a,b and 5а,b to displace propidium from the peripheral anionic site of EeAChE and scavenge free radicals in the ABTS test.


This work was performed within the framework of the RFBR grant #17-03-00984-а (synthesis, structure determination, as well as study of the esterase profile of the compounds obtained and molecular modeling ). Displacement of propidium iodide from the PAS of EeAChE and ABTS scavenging activity of conjugates were studied in the framework of the Russian State assignment № 0090-2017- 0019. The equipment of the Center for the collective use of IPAС RAS was used. Molecular modeling was carried out using the equipment of the Center for the collective use of super high-performance computing resources of the Lomonosov Moscow State University.


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