Sinteza i strukturna karakterizacija novih purinskih bioizostera s potencijalnom biološkom aktivnošću

master's thesis

• Title (english): Synthesis and structural characterization of novel purine bioisosteres with potential biological activity
• Author: Leon Sačer
• Mentor: Silvana Raić-Malić (mentor)
• Committee member: Silvana Raić-Malić (predsjednik povjerenstva)
• Committee member: Tatjana Gazivoda Kraljević (član povjerenstva)
• Committee member: Danijela Ašperger (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2023-09-28, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Purini i purinski bioizosteri važni su spojevi u medicinskoj kemiji zbog njihove uloge u različitim staničnim procesima te njihovog značaja u razvoju lijekova. Njihova fizikalno-kemijska svojstva i širok raspon bioloških aktivnosti kao što je antitumorska i antivirusna aktivnost čine ih bitnim farmakoforima za razvoj lijekova. U ovom radu sintetizirani su izoksazolni derivati purina i 7-deazapurina reakcijom bazno katalizirane 1,3-dipolarne cikloadicije N-propargiliranih heterocikličkih derivata i nitrilnih oksida koji su prethodno pripravljeni in situ iz hidroksimoilnih klorida. Sintetizirani spojevi 33−38 u daljnjem su stupnju modificirani na položaju C-6 purinske jezgre kako bi se vidio utjecaj ovakve kemijske transformacije na biološku aktivnost. Za tu su svrhu provedene Suzuki-Miyaurine i Sonogashirine reakcije katalizirane paladijem koje su potpomognute mikrovalnim zračenjem. Piridinski derivati supstituirani na izoksazolnom prstenu nadalje su korišteni kao ligandi za sintezu renij(I) trikarbonilnih metalnih kompleksa. Ovakvo uvođenje metala u strukturu potencijalno biološki aktivnih spojeva može povoljno utjecati na aktivnost te poboljšati fizikalno-kemijska svojstva nastalih metalnih kompleksa. Svi sintetizirani spojevi i metalni kompleksi strukturno su okarakterizirani pomoću spektroskopije 1H i 13C NMR, UV-Vis i IR, a struktura metalnog kompleksa 35a dodatno je potvrđena rendgenskom strukturnom analizom.

Abstract (english)

Due to their crucial function in numerous biological processes and their usefulness in the development of drugs, purines and purine bioisosteres are significant compounds in medicinal chemistry. Their physicochemical properties and wide range of biological activities, such as antitumor and antiviral activity make them essential pharmacophores for the drug development. In this work, various isoxazole derivatives of purine and 7-deazapurine were synthesized. The target compounds were synthesized by a base-catalyzed 1,3-dipolar cycloaddition reaction between N-propargylated heterocycles and nitrile oxides generated in situ from hydroxymoyl chlorides. The synthesized compounds 33−38 were then modified at the C-6 position of the purine in order to improve biological activity. Suzuki-Miyaura and Sonogashira palladium catalyzed cross-coupling reactions were performed under microwave irradiation. Pyridine-substituted isoxazole derivatives were used subsequently as ligands for the synthesis of rhenium(I) tricarbonyl metal complexes. The introduction of metals into the structure of potentially biologically active compounds can favorably influence the activity and improve the physicochemical properties. All synthesized compounds and metal complexes were structurally characterized using 1H and 13C NMR, UV-Vis and IR spectroscopy, while the structure of metal complex 35a was additionally confirmed by X-ray structural analysis.

• Keywords: izoksazol; metalni kompleksi; purin; purinski bioizosteri; trikarbonilrenij(I) kompleksi
• Keywords (english): isoxazole; metal complexes; purine; purine bioisosteres; tricarbonylrhenium(I) complexes
• Language: croatian
• URN:NBN: urn:nbn:hr:149:032149
• Project: Number: IP-2018-01-4682; Title: Novi spojevi temeljeni na bioizosterima purina za ispitivanje njihovih antitumorskih i antipatogenih djelovanja; Acronym: PurBioCaPa; Leader: Silvana Raić-Malić; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• 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: sveučilišni/a magistar/magistra primijenjene kemije (sveučilišni/a magistar/magistra primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-09-01
• Created on: 2023-11-24 09:53:01