Priprava i biološka aktivnost novih tienobenzo-triazola

master's thesis

• Title (english): Synthesis and biological activity of thienobenzo-triazoles
• Author: Ida Selec
• Mentor: Irena Škorić (mentor)
• Mentor: Irena Ćaleta (komentor)
• Committee member: Irena Škorić (predsjednik povjerenstva)
• Committee member: Dragana Vuk (član povjerenstva)
• Committee member: Irena Ćaleta (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2023-09-15, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Cilj rada bio je sintetizirati nove tienobenzo-triazole te ispitati njihovu inhibicijsku potenciju prema kolinesterazama. Također je procijenjena selektivnost njihove inhibicije, a rezultati su interpretirani molekularnim modeliranjem. Uspješno je sintetizirano 15 novih spojeva koji se razlikuju po supstituentu pričvršćenom na triazolni prsten ili po aromatičnosti središnjeg prstena. Fotociklizacijskim putem sintetiziran je jedan spoj 1, dok je alternativni put dao širok spektar molekula dihidro-tienobenzo-triazola i aromatiziranih tienobenzo-triazola 2-15.
Većina novih molekula pokazala je bolju inhibicijsku potenciju prema butirilkolinesterazi
(BChE – eng. butyrylcholinesterase). Računalne studije ukazuju na povezivanje
tienobenzo-triazola s kolinesterazama preko vodikovih veza koje uključuju jedan od dušika triazola, smještenih između aromatskih ostataka liganda i aromatskih ostataka aktivnih mjesta kolinesteraza. Također su prisutne i alkilne interakcije. Molekularno pristajanje omogućuje uvid u strukturu dobivenih kompleksa i identifikaciju stabilizirajućih interakcija između enzima i potencijalnog inhibitora kolinesteraze. Novosintetizirani tienobenzo-triazoli pokazali su dobre karakteristike za budući dizajn inhibitora kolinesteraza i traženje terapeutika za liječenje neuroloških poremećaja.

Abstract (english)

The aim of this study was to synthesize new thienobenzo-triazoles and to examine their inhibitory potency towards cholinesterases. The selectivity of their inhibition was also assessed, and the results were interpreted by molecular modeling. 15 new compounds have been successfully synthesized, differing in the substituent attached to the triazole ring or by the aromaticity of the central ring. A single compound 1 was synthesized by photocyclization route, while the alternative pathway gave a wide range of molecules of
dihydro-thienobenzo-triazole and aromatized thienobenzo-triazole 2-15. Most of the new molecules showed better inhibitory potency towards butyrylcholinesterase (BChE). Computational studies suggest that thienobenzo-triazole and cholinesterases are linked via hydrogen bonds involving one of the triazole nitrogen, located between aromatic ligand residues and aromatic residues of the active cholinesterase sited. Alkyl interactions are also present. Molecular docking gives insight into the structure of the obtained complexes and the identification of stabilizing interactions between enzymes and a potential cholinesterase inhibitor. The newly synthesized thienobenzo-triazoles showed good characteristics for the future design of cholinesterase inhibitors and the search for therapeutics for the treatment of neurological disorders.

• Keywords: alternativna sinteza; fotociklizacija; inhibicija; kolinesteraze; tienobenzo-triazoli
• Keywords (english): alternative synthesis; photocyclization; inhibition; cholinesterases; thienobenzo-triazoles
• Language: croatian
• URN:NBN: urn:nbn:hr:149:434231
• Study programme: Title: Applied Chemistry - Graduate study; specializations in: Environmental chemistry and green technologies, Advanced materials and technologies, Applied organic chemistry; Course: Applied organic chemistry; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra primijenjene kemije (magistar/magistra primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-09-21 13:16:11