Sinteza, računalno modeliranje i fotokemija novih 1,3-tiazolo-tienostilbena

master's thesis

• Title (english): Synthesis, computational modeling and photochemistry of new 1,3-thiazolo-thienostilbenes
• Author: Ema Đurčević
• Mentor: Irena Škorić (mentor)
• Mentor: Danijela Barić (komentor)
• Committee member: Irena Škorić (predsjednik povjerenstva)
• Committee member: Dragana Vuk (član povjerenstva)
• Committee member: Danijela Barić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2023-09-07, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Inhibitori enzima kolinesteraza prepoznaju se kao jedan od glavnih izbora za smanjenje simptoma Alzheimerove bolesti, četvrte bolesti po redu koja uzrokuje smrt u razvijenim zemljama, zbog toga što uzrokuje da se razina neurotransmitera acetilkolina u kolinergičnim sinapsama povećava. U svrhu pronalaska još učinkovitijih inhibitora kolinesteraza, sintetizirani su u ovom radu novi derivati 1,3-tiazolo-tienostilbena 1-9 i njihovi fotoprodukti 10-16. Spojevi 1-5, 7 i 8 sintetizirani su Wittigovom reakcijom s tiofenskom fosfonijevom soli. Sinteza 1,3-tiazolo-tienostilbena 6 provela se amidacijom spoja 5 uz acetanhidrid, dok se spoj 9 sintetizirao Büchwald-Hartwigovim aminiranjem. Svi derivati 1-9 dobiveni su kao smjese cis- i trans- izomera. Na dobivenim spojevima 1-4 i 6-9 provedene su reakcije elektrociklizacije u fotokemijskom reaktoru Rayonet s 10 UV lampi na 300 nm, čime su se dobili novi derivati tienobenzo-tiazola 10-16. Sintetizirani su i novi derivati tienobenzo-triazola 23-25 nizom od tri reakcije. Svi dobiveni spojevi pročišćeni su kolonskom kromatografijom na silika-gelu. Čisti spojevi okarakterizirani su spektroskopskim metodama i poslani su na ispitivanje biološke aktivnosti. Koristile su se 1H i 13C NMR tehnike, UV-Vis spektroskopija, masena spektrometrija i HRMS analiza. Provelo se i računalno istraživanje kojim su proučavane geometrije i elektronske strukture dobivenih tiazola, te molekulski docking kojim su se identificirale interakcije između enzima i potencijalnog inhibitora s ciljem predviđanja jačine inhibicije.

Abstract (english)

Inhibitors of enzymes cholinesterases are recognized as one of the main choices for reducing symptoms of Alzheimer's disease, the fourth leading cause of death in developed countries, because they cause an increase in the level of acetylcholine neurotransmitter in cholinergic synapses. In order to discover even more effective cholinesterase inhibitors, new derivatives of 1,3-thiazole-thienostilbenes 1-9 and their photoproducts 10-16 were synthesized in this study. Compounds 1-5, 7, and 8 were synthesized through the Wittig reaction with thiophene phosphonium salt. The synthesis of 1,3-thiazole-thienostilbene 6 was carried out by amidation of compound 5 with acetic anhydride, while compound 9 was synthesized by Büchwald-Hartwig amination. All derivatives 1-9 were gained as mixtures of cis- and trans-isomers. The obtained compounds 1-4 and 6-9 underwent electrocyclic reactions in a Rayonet photoreactor equipped with 10 UV lamps at 300 nm, resulting in new derivatives of thienobenzo-thiazoles 10-16. New derivatives of thienobenzo-triazoles 23-25 were also synthesized, through a series of three reactions. All obtained compounds were purified using column chromatography on silica gel. Pure compounds were characterized by spectroscopic methods and sent for biological activity testing. 1H and 13C NMR techniques, UV-Vis spectroscopy, mass spectrometry, and HRMS analyses were used. Computational research was also conducted to study the geometries and electronic structures of the obtained thiazoles, and molecular docking was performed to identify interactions between the enzyme and the potential inhibitor in order to predict the strength of the inhibition.

• Keywords: Alzheimerova bolest; elektrociklizacija; inhibicija kolinesteraze; molekulski docking; 1 3-tiazolo-tienostilbeni; Wittigova reakcija
• Keywords (english): Alzheimer's disease; electrocyclization; inhibition of cholinesterases; molecular docking; 1 3-thaizolo-thienostilbenes; Wittig reaction
• Language: croatian
• URN:NBN: urn:nbn:hr:149:578746
• 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: 2023-09-14 13:02:59