Novi 2-supstituirani derivati benzimidazola kao potencijalni antitumorski agensi: sinteza i strukturna karakterizacija

master's thesis

• Title (english): Novel 2-substituted benzimidazole derivatives as potential antitumor agents: synthesis and structural characterization
• Author: Anja Rakas
• Mentor: Tatjana Gazivoda Kraljević (mentor)
• Committee member: Tatjana Gazivoda Kraljević (predsjednik povjerenstva)
• Committee member: Silvana Raić-Malić (član povjerenstva)
• Committee member: Dragana Mutavdžić Pavlović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2020-09-23, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U ovom radu opisana je sinteza novih derivata benzimidazola i strukturna karakterizacija 1H i 13C-NMR spektroskopijom s ciljem ispitivanja njihovog antitumorskog i antibakterijskog djelovanja. Ključni prekursori 4-O-alkilirani benzaldehidi (1-6) pripravljeni su reakcijom O-alkiliranja 4-hidroksibenzaldehida a odgovarajućim haloalkilirajućim reagensima u acetonitrilu, uz K2CO3 kao bazu. Reakcijom N-klormorfolina s natrijevim azidom priređen je N-azidoetilmorfolin (7). O-alkiliranjem 4-hidroksibenzaldehida s propargil-bromidom u suhom etanolu uz K2CO3 kao bazu sintetizirani su 4-O-propargilbenzaldehidi (8 i 9). Huisgenovom 1,3-dipolarnom ciloadicijom 4-O-propargilbenzaldehida (8 i 9) s N-azidoetilmorfolinom (7) uz Cu(OAc)2 kao katalizator pripavljeni su 1,2,3-triazolni derivati benzaldehida (10 i 11). Reakcijom ciklizacije potpomognutom ultrazvukom O-alkiliranih benzaldehida (1-6) uz K2CO3 kao bazu i Na2S2O5 priređeni su derivati benzimidazola s odgovarajućim arilnim supstituentima u položaju 2 benzimidazolnog prstena (12-14, 16-27, 29-35). Strukture svih pripravljenih spojeva potvrđene su 1H i 13C-NMR spektroskopijom. Farmakološki učinci i moguće biološke mete novopripravljenih spojeva predviđene su in silico analizom (PASS).

Abstract (english)

This paper describe the synthesis of novel benzaldehyde derivatives and structural characterization by 1H and 13C-NMR spectroscopy in order to examine their antitumor and antibacterial activities. Key precursors 4-O-alkylbenzaldehydes (1-6) were prepared by reaction of O-alkylation 4-hydroxybenzaldehyde with corresponding haloalkylating reagents in the presence K2CO3 as base. In reaction of N-chloromorpholine with sodium azide N-azidoethylmorpholine (7) was obtained. O-alkylation reaction of 4-hydroxybenzaldehyde with propargyl bromide in dry ethanol with K2CO3 as a base gave 4-O-alkylbenzaldehydes (8-9). 1,2,3-triazole benzaldehyde derivatives (10 i 11) were synthesized by Huisgen 1,3-dipolar cycloaddition of O-alkylbenzaldehydes (8 i 9) and N-azidoethylmorpholine (7) in the presence of Cu(OAc)2 as catalyst. Benzimidazole derivatives substituted with appropriate aril substituents in position 2 of benzimidaze ring (12-14, 16-27, 29-35) were prepared by cyclization reaction of O-alkylbenzaldehydes (1-6) with K2CO3 as base and Na2S2O5 supported with ultrasound of The structures of all newly prepared compounds were confirmed by 1H and 13C-NMR spectroscopy. Pharmacological effects and possible biological targets of novel compounds are predicted by in silico analysis (PASS).

• Keywords: benzimidazol; 1 2 3-triazol; Huisgenova 1 3-diplarna cikloadicija; reakcije potpomognute ultrazvukom
• Keywords (english): benzimidazole; 1 2 3-triazole; Huisgen 1 3-dipolar cycloaddition; ultrasound assisted reactions
• Language: croatian
• URN:NBN: urn:nbn:hr:149:291119
• 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: Environmental Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka ekoinženjerstva (magistar/magistra inženjer/inženjerka ekoinženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-10-01
• Created on: 2022-04-13 12:52:23