Sinteza novih izoksazolnih i amidoksimskih bioizostera purina s antitripanosomskim djelovanjem

master's thesis

• Title (english): Synthesis of new isoxazole and amidoxime purine bioisosteres with antitrypanosomal activity
• Author: Lorena Damjanović
• 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: 2024-12-17, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U ovom radu opisana je sinteza novog amidoksim-supstituiranog derivata benzotiazola 5 te novih hibrida benzimidazola i izoksazola 19a–e. Derivat 5 dobiven je višestupanjskom sintezom iz 4-aminobenzonitrila. Utvrđeno je da derivat 5 pokazuje antitripanosomsku aktivnost s IC50 vrijednosti od 0.92 μM, uz indeks selektivnosti 18. Zbog izražene biološke aktivnosti i visoke selektivnosti, derivat je korišten kao ligand za sintezu metalnih kompleksa renija(I) i mangana(I). N-propargilirani derivat benzimidazola 12 dobiven je reakcijom alkiliranja dok su odgovarajući oksimi 18a–e, potrebni za sintezu izoksazolnih derivata priređeni reakcijom kloriranja odgovarajućih aldoksima. Ciljani derivati 19a–e priređeni su bazno-kataliziranom 1,3-dipolarnom cikloadicijom iz N-propargiliranog derivata 12 i kloriranih oksima 18a–e. Strukture novosintetiziranih spojeva potvrđene su spektroskopijom 1H i 13C NMR. Naknadno će se provesti antitripanosomska ispitivanja ostalih novosintetiziranih spojeva.

Abstract (english)

In this work, the synthesis of novel amidoxime derivatives of benzothiazole 5 and novel benzimidazole derivatives linked via an isoxazole spacer (19a–e) is described. Derivative 5 was obtained from 4-aminobenzothiazole by a multi-step synthesis. Derivative 5 was evaluated for its antitrypanosomal activity and gave an IC50 value of 0.92 μM against T. brucei, with a selectivity index of 18. Due to its significant biological activity and high selectivity, the derivative was used as a ligand for the synthesis of rhenium(I) and manganese(I) metal complexes. N-Propargylated benzimidazole derivative 12 was prepared by alkylation reaction. The corresponding oximes 18a–e for the synthesis of isoxazole derivatives were synthesized by the chlorination reaction of corresponding aldoximes.
The targer isoxazole derivatives 19a–e were prepared by base-catalyzed 1,3-dipolar cycloaddition of N-propargylated benzimidazole derivative 12 and chlorinated oximes 18a–e. The structures of all compounds were determined by 1H NMR and 13C NMR spectroscopy. Antitrypanosomal evaluations of these compounds will be performed.

• Keywords: benzotiazol; benzimidazol; izoksazol; 1 3-dipolarna cikloadicija; purin; purinski bioizosteri
• Keywords (english): benzothiazole; benzimidazole; isoxazole; 1 3-dipolar cycloaddition; purine; purine bioisoteres
• Language: croatian
• URN:NBN: urn:nbn:hr:149:203445
• Project: Number: IP-2022-10-9420; Title: Novi N‐heterocikli i njihovi kompleksi s antitumorskim i antitripanosomskim djelovanjem; Title: Novel N-heterocycles and their metal complexes with anticancer and antitrypanosomal activity; Acronym: NHet&MetCom Project; Leader: Silvana Raić-Malić; Jurisdiction: Croatia; Funder: Hrvatska zaklada za znanost; Funding stream: Research Projects
• 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: 2026-01-01
• Created on: 2024-12-19 07:55:55