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Sinteza zaviralcev napetostno odvisnega protonskega kanala Hv1 s 5-benziloksifenil-2-aminoimidazolnim skeletom
ID Mlakar, Živa (Author), ID Zidar, Nace (Mentor) More about this mentor... This link opens in a new window, ID Piga, Martina (Comentor)

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Abstract
Rak je eden vodilnih vzrokov smrti po svetu, saj letno povzroči približno 10 milijonov smrti. V tej magistrski nalogi smo raziskovali nove pristope k zdravljenju raka z osredotočanjem na napetostno odvisne protonske kanale Hv1, ki so pogosto prekomerno izraženi v različnih rakavih celicah. Kanali Hv1 sodelujejo pri regulaciji pH, proliferaciji celic, imunskem odzivu ter tvorbi reaktivnih kisikovih zvrsti (ROS). Njihovo zaviranje lahko zmanjša oksidativni stres, zavre metastaziranje in povzroči apoptozo rakavih celic. Na osnovi strukture znane spojine NZ-49 smo zasnovali, sintetizirali in analizirali pet novih derivatov z 5-benziloksifenil-2-aminoimidazolnim skeletom. Strukturo in čistost spojin smo potrdili z uporabo UHPLC, IR, NMR in HRMS metod. Biološko vrednotenje je bilo opravljeno z elektrofiziološko metodo na celicah CHO, ki izražajo človeški Hv1 kanal. Rezultati so pokazali, da večina sintetiziranih spojin učinkoviteje zavira Hv1 kot izhodna spojina NZ-49, kar kaže na njihov potencial kot terapevtska sredstva proti raku.

Language:Slovenian
Keywords:napetostno odvisni protonski kanal Hv1, rak, sinteza, zaviralec
Work type:Master's thesis/paper
Organization:FFA - Faculty of Pharmacy
Year:2025
PID:20.500.12556/RUL-168772 This link opens in a new window
Publication date in RUL:24.04.2025
Views:370
Downloads:197
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Secondary language

Language:English
Title:Synthesis of voltage-gated proton channel Hv1 inhibitors with 5-benzyloxyphenyl-2-aminoimidazole scaffold
Abstract:
Cancer is one of the leading causes of death worldwide, accounting for approximately 10 million deaths annually. In this master's thesis, we explored novel approaches to cancer treatment by focusing on voltage-gated proton channels Hv1, which are often overexpressed in various cancer cells. Hv1 channels play a role in regulating pH, cell proliferation, immune response, and the production of reactive oxygen species (ROS). Inhibition of these channels can reduce oxidative stress, suppress metastasis, and induce apoptosis in cancer cells. Based on the structure of the known compound NZ-49, we designed, synthesized, and analyzed five new derivatives featuring a 5-benzyloxyphenyl-2-aminoimidazole scaffold. The structure and purity of the compounds were confirmed using UHPLC, IR, NMR, and HRMS techniques. Biological evaluation was performed using the patch-clamp electrophysiological method on CHO cells expressing the human Hv1 channel. The results showed that most of the synthesized compounds inhibited Hv1 more effectively than the reference compound NZ-49, indicating their potential as therapeutic agents against cancer.

Keywords:voltage gated proton channel Hv1, cancer, synthesis, inhibitor

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