Dizajn i sinteza novih malih molekula kao inhibitora Chikungunya virusa

master's thesis

• Title (english): Design and synthesis of new small molecules as Chikungunya virus inhibitors
• Author: Tajana Iva Pejaković
• Mentor: Mirza Bojić (mentor)
• Committee member: Mirza Bojić (predsjednik povjerenstva)
• Committee member: Željan Maleš (član povjerenstva)
• Committee member: Mirela Matić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medicinal chemistry); Zagreb
• Defense date and country: 2018-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

The worldwide impact of Chikungunya virus (CHIKV) and the emergence of new transmission strains in Europe and Americas shows that arthritogenic Alphaviruses infections pose a serious public health issue. There are no vaccines or antivirals available for the prevention or treatment of CHIKV infection, and most of the treatment regimens are symptomatic and based on the clinical manifestations. The purpose of this thesis was to synthesize new carbonyl compounds that could act as CHIKV inhibitors. Compound 4 was prepared by nitration with concentrated sulfuric acid using the commercially available 4'-chloroacetophenone. Compound 3 was prepared using Suzuki-Miyaura cross coupling reaction, while compound 2 was prepared using PPh3-mediated reductive cyclization. Both of the compounds 1a and 1b were prepared with base catalyzed aldol reaction, using the previously synthesized compound 2 and commercially available benzaldehyde and 3-bromo-4-methoxybenzaldehyde. The structures of the compounds were confirmed by usual analytical and spectroscopic methods (IR and 1H NMR spectroscopy).

Abstract (croatian)

Utjecaj Chikungunya virusa (CHIKV) širom svijeta te pojavljivanje novih prijenosnih sojeva u Europi i Americi pokazuje koliko ozbiljni javnozdravstveni problem predstavljaju infekcije artritogenim Alphavirus-ima. Ne postoji cjepivo niti antivirotik na tržištu koji bi se koristio u prevenciji ili liječenju CHIKV infekcije, a većina terapije je simptomatska i temelji se na kliničkim manifestacijama. Cilj ovog rada je bio sintetizirati nove derivate karbonila koji bi mogli djelovati kao CHIKV inhibitori. Spoj 4 je pripremljen nitracijom komercijalno dostupnog 4'-kloracetofenona koristeći koncentriranu sumpornu kiselinu. Spoj 3 pripremljen je Suzuki-Miyaura reakcijskim mehanizmom, dok je spoj 2 pripremljen uz PPh3-potpomognutu reduktivnu ciklizaciju. Spojevi 1a i 1b su sintetizirani bazičnom aldolnom kondenzacijom, koristeći prethodno pripremljeni spoj 2 i komercijalno dostupni benzaldehid i 3-bromo-4-metoksibenzaldehid. Strukture svih sintetiziranih spojeva potvrđene su uobičajenim spektroskopskim metodama (IR, 1H NMR).

• Keywords: Chikungunya virus; carbonyl; inhibitor; synthesis
• Keywords (croatian): Chikungunya virus; karbonil; inhibitor; sinteza
• Language: english
• URN:NBN: urn:nbn:hr:163:459130
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-04-22 11:43:58