Ispitivanje citotoksičnosti derivata itakonske kiseline kao potencijalnih citostatika na THP-1 staničnoj liniji

master's thesis

• Title (english): Cytotoxicity testing of itaconic acid derivatives as potential cytostatics on THP-1 cell line
• Author: Mirela Šalov
• Mentor: Karmela Barišić (mentor)
• Mentor: Mario Matijašić (mentor)
• Committee member: Karmela Barišić (predsjednik povjerenstva)
• Committee member: Donatella Verbanac (član povjerenstva)
• Committee member: Mario Matijašić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2021-09-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Razvoj novoga lijeka dugotrajan je i skup proces. Nakon što se izabere bolest za koju će se razvijati novi lijek i identificira meta na koju će lijek djelovati, različitim biološkim testovima ispituje se farmakološki učinak molekula. Optimiranjem strukture lijeka poboljšavaju se farmakodinamička i farmakokinetička svojstva. Ukoliko lijek prođe pretkliničku i kliničku fazu razvoja, pokreće se postupak registracije lijeka. Tijekom razvoja koriste se brojne in vitro, in vivo i in silico metode. Testovi citotoksičnosti korisni su alati u otkrivanju potencijalnih citostatika. U tu svrhu, zbog jednostavnosti korištenja i lakoće manipuliranja, često se koriste stanične linije. Uslijed velikog broja oboljelih od malignih bolesti i neadekvatne postojeće terapije, postoji stalna potreba za razvojem učinkovitijih i selektivnijih citostatika.
U ovom su radu ispitani derivati itakonske kiseline kao potencijalni citostatici. Ispitivanje je provedeno na stanicama akutne monocitne leukemije THP-1. Nakon što su stanice tretirane otopinom sintetskih spojeva u različitim koncentracijama, određena je vijabilnost stanica pomoću MTS testa. Rezultati su prikazani u obliku IC50 vrijednosti. Svi ispitivani spojevi pokazuju citotoksičnost za stanice, a najučinkovitiji je spoj MI5, konjugat itakonske kiseline i klorokina.

Abstract (english)

The development of a new drug is a time consuming and expensive process. Once the disease for which the new drug will be developed is selected and the target on which the drug will act is identified, the pharmacological effect of the molecules is examined by various biological tests. Optimizing the drug structure improves the pharmacodynamic and pharmacokinetic properties. If the drug passes the preclinical and clinical phase of development, the drug registration procedure is initiated. Numerous in vitro, in vivo and in silico methods are used during development. Cytotoxicity tests are useful tools in detecting potential cytostatics. They use cell lines due to the simplicity and ease of manipulation. Considering the large number of patients with malignant diseases and inadequate existing therapy, there is a constant need to develop more effective and selective cytostatics.
This thesis analyzed itaconic acid derivatives as potential cytostatics. The study was performed on acute monocyte leukemia THP-1 cells. After the cells were treated with a solution of synthetic compounds at different concentrations, cell viability was determined by using the MTS assay. The results are presented in the form of IC50 values. All test compounds were cytotoxic for cells but the most effective compound was MI5 which is a conjugate of itaconic acid and chloroquine.

• Keywords: citotoksičnost; derivati itakonske kiseline; THP-1 stanična linija
• Keywords (english): cytotoxicity; itaconic acid derivates; THP-1 cell line
• Language: croatian
• URN:NBN: urn:nbn:hr:163:412908
• 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: 2022-02-08 14:02:44