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Your search keyword '"Možina, Štefan"' showing total 15 results
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15 results on '"Možina, Štefan"'

1. Correction: Gubič et al. Design of New Potent and Selective Thiophene-Based KV1.3 Inhibitors and Their Potential for Anticancer Activity. Cancers 2022, 14, 2595

Author

Gubič, Špela, primary, Hendrickx, Louise Antonia, additional, Shi, Xiaoyi, additional, Toplak, Žan, additional, Možina, Štefan, additional, Theemsche, Kenny M. Van, additional, Pinheiro-Junior, Ernesto Lopes, additional, Peigneur, Steve, additional, Labro, Alain J., additional, Pardo, Luis A., additional, Tytgat, Jan, additional, Tomašič, Tihomir, additional, and Peterlin Mašič, Lucija, additional

Published
2023
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2. New Dual Inhibitors of Bacterial Topoisomerases with Broad-Spectrum Antibacterial Activity and In Vivo Efficacy against Vancomycin-Intermediate Staphylococcus aureus

Author

Durcik, Martina, primary, Cotman, Andrej Emanuel, additional, Toplak, Žan, additional, Možina, Štefan, additional, Skok, Žiga, additional, Szili, Petra Eva, additional, Czikkely, Márton, additional, Maharramov, Elvin, additional, Vu, Thu Hien, additional, Piras, Maria Vittoria, additional, Zidar, Nace, additional, Ilaš, Janez, additional, Zega, Anamarija, additional, Trontelj, Jurij, additional, Pardo, Luis A., additional, Hughes, Diarmaid, additional, Huseby, Douglas, additional, Berruga-Fernández, Tália, additional, Cao, Sha, additional, Simoff, Ivailo, additional, Svensson, Richard, additional, Korol, Sergiy V., additional, Jin, Zhe, additional, Vicente, Francisca, additional, Ramos, Maria C., additional, Mundy, Julia E. A., additional, Maxwell, Anthony, additional, Stevenson, Clare E. M., additional, Lawson, David M., additional, Glinghammar, Björn, additional, Sjöström, Eva, additional, Bohlin, Martin, additional, Oreskär, Joanna, additional, Alvér, Sofie, additional, Janssen, Guido V., additional, Sterk, Geert Jan, additional, Kikelj, Danijel, additional, Pal, Csaba, additional, Tomašič, Tihomir, additional, and Peterlin Mašič, Lucija, additional

Published
2023
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3. Discovery and Hit-to-Lead Optimization of Benzothiazole Scaffold-Based DNA Gyrase Inhibitors with Potent Activity against Acinetobacter baumannii and Pseudomonas aeruginosa

Author

Cotman, Andrej Emanuel, primary, Durcik, Martina, additional, Benedetto Tiz, Davide, additional, Fulgheri, Federica, additional, Secci, Daniela, additional, Sterle, Maša, additional, Možina, Štefan, additional, Skok, Žiga, additional, Zidar, Nace, additional, Zega, Anamarija, additional, Ilaš, Janez, additional, Peterlin Mašič, Lucija, additional, Tomašič, Tihomir, additional, Hughes, Diarmaid, additional, Huseby, Douglas L., additional, Cao, Sha, additional, Garoff, Linnéa, additional, Berruga Fernández, Talía, additional, Giachou, Paraskevi, additional, Crone, Lisa, additional, Simoff, Ivailo, additional, Svensson, Richard, additional, Birnir, Bryndis, additional, Korol, Sergiy V., additional, Jin, Zhe, additional, Vicente, Francisca, additional, Ramos, Maria C., additional, de la Cruz, Mercedes, additional, Glinghammar, Björn, additional, Lenhammar, Lena, additional, Henderson, Sara R., additional, Mundy, Julia E. A., additional, Maxwell, Anthony, additional, Stevenson, Clare E. M., additional, Lawson, David M., additional, Janssen, Guido V., additional, Sterk, Geert Jan, additional, and Kikelj, Danijel, additional

Published
2023
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4. Design of New Potent and Selective Thiophene-Based KV1.3 Inhibitors and Their Potential for Anticancer Activity

Author

Gubič, Špela, primary, Hendrickx, Louise Antonia, additional, Shi, Xiaoyi, additional, Toplak, Žan, additional, Možina, Štefan, additional, Theemsche, Kenny M. Van, additional, Pinheiro-Junior, Ernesto Lopes, additional, Peigneur, Steve, additional, Labro, Alain J., additional, Pardo, Luis A., additional, Tytgat, Jan, additional, Tomašič, Tihomir, additional, and Mašič, Lucija Peterlin, additional

Published
2022
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5. Design of New Potent and Selective Thiophene-Based K V 1.3 Inhibitors and Their Potential for Anticancer Activity.

Author

Gubič, Špela, Hendrickx, Louise Antonia, Shi, Xiaoyi, Toplak, Žan, Možina, Štefan, Theemsche, Kenny M. Van, Pinheiro-Junior, Ernesto Lopes, Peigneur, Steve, Labro, Alain J., Pardo, Luis A., Tytgat, Jan, Tomašič, Tihomir, and Mašič, Lucija Peterlin

Subjects
SULFUR compounds, ANIMAL experimentation, ANTINEOPLASTIC agents, DRUG design, APOPTOSIS, CELL proliferation, TUMORS, MOLECULAR structure, POTASSIUM antagonists, PHARMACODYNAMICS
Abstract

Simple Summary: In this article, we describe the discovery of a new class of potent and selective thiophene-based inhibitors of the voltage-gated potassium channel KV1.3 and their potential to induce apoptosis and inhibit proliferation. The KV1.3 channel has only recently emerged as a molecular target in cancer therapy. The most potent KV1.3 inhibitor 44 had an IC50 KV1.3 value of 470 nM (oocytes) and 950 nM (Ltk− cells) and appropriate selectivity for other KV channels. New KV1.3 inhibitors significantly inhibited proliferation of Panc-1 cells and KV1.3 inhibitor 4 induced significant apoptosis in tumor spheroids of Colo-357 cells. The voltage-gated potassium channel KV1.3 has been recognized as a tumor marker and represents a promising new target for the discovery of new anticancer drugs. We designed a novel structural class of KV1.3 inhibitors through structural optimization of benzamide-based hit compounds and structure-activity relationship studies. The potency and selectivity of the new KV1.3 inhibitors were investigated using whole-cell patch- and voltage-clamp experiments. 2D and 3D cell models were used to determine antiproliferative activity. Structural optimization resulted in the most potent and selective KV1.3 inhibitor 44 in the series with an IC50 value of 470 nM in oocytes and 950 nM in Ltk− cells. KV1.3 inhibitor 4 induced significant apoptosis in Colo-357 spheroids, while 14, 37, 43, and 44 significantly inhibited Panc-1 proliferation. [ABSTRACT FROM AUTHOR]

Published
2022
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6. Practical Synthesis and Application of Halogen-Doped Pyrrole Building Blocks

Author

Cotman, Andrej Emanuel, primary, Guérin, Thomas, additional, Kovačević, Ivana, additional, Benedetto Tiz, Davide, additional, Durcik, Martina, additional, Fulgheri, Federica, additional, Možina, Štefan, additional, Secci, Daniela, additional, Sterle, Maša, additional, Ilaš, Janez, additional, Zega, Anamarija, additional, Zidar, Nace, additional, Mašič, Lucija Peterlin, additional, Tomašič, Tihomir, additional, Leroux, Frédéric R., additional, Hanquet, Gilles, additional, and Kikelj, Danijel, additional

Published
2021
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7. 3D Pharmacophore-Based Discovery of Novel KV10.1 Inhibitors with Antiproliferative Activity

Author

Toplak, Žan, primary, Hendrickx, Louise Antonia, additional, Gubič, Špela, additional, Možina, Štefan, additional, Žegura, Bojana, additional, Štern, Alja, additional, Novak, Matjaž, additional, Shi, Xiaoyi, additional, Peigneur, Steve, additional, Tytgat, Jan, additional, Tomašič, Tihomir, additional, Pardo, Luis A., additional, and Mašič, Lucija Peterlin, additional

Published
2021
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9. Synthesis of alpha-Iodoketones from Allylic Alcohols through Aerobic Oxidative Iodination

Author

Sanz-Marco, Amparo, Možina, Štefan, Martinez-Erro, Samuel, Iskra, Jernej, Martín‐Matute, Belén, Sanz-Marco, Amparo, Možina, Štefan, Martinez-Erro, Samuel, Iskra, Jernej, and Martín‐Matute, Belén

Abstract

An efficient method for the synthesis of alpha-iodoketones from allylic alcohols and elemental iodine is reported. We show in this paper that the isomerization of allylic alcohols catalyzed by iridium(III) complexes can be combined with an aerobic oxidative iodination protocol, resulting in a straightforward method for the synthesis of a wide range of alpha-iodoketones as single constitutional isomers and in high yields under mild reaction conditions.

Published
2018
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11. Correction: Gubič et al. Design of New Potent and Selective Thiophene-Based K V 1.3 Inhibitors and Their Potential for Anticancer Activity. Cancers 2022, 14 , 2595.

Author

Gubič, Špela, Hendrickx, Louise Antonia, Shi, Xiaoyi, Toplak, Žan, Možina, Štefan, Theemsche, Kenny M. Van, Pinheiro-Junior, Ernesto Lopes, Peigneur, Steve, Labro, Alain J., Pardo, Luis A., Tytgat, Jan, Tomašič, Tihomir, and Peterlin Mašič, Lucija

Subjects
SULFUR compounds, ANTINEOPLASTIC agents, DRUG design, TUMORS, POTASSIUM antagonists, PHARMACODYNAMICS
Published
2023
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13. Dual Catalysis for the Aerobic Oxidation of Benzyl Alcohols - Nitric Acid and Fluorinated Alcohol.

Author

Možina, Štefan, Stavber, Stojan, and Iskra, Jernej

Subjects
*BENZYL alcohol, *OXIDATION of chemical alcohols, *NITRIC acid, *OXIDATION, *CHEMICAL reactions
Abstract

Benzyl alcohols were oxidized with oxygen to aldehydes in excellent yields with high selectivities at room temperature. Dual catalysis was operative with HNO3 as the oxidant and precursor of the nitrogen oxides and with the use of 1,1,1,3,3,3-hexafluoro-2-propanol as a template catalyst and solvent. Fluorinated alcohols also increased the selectivity by inhibiting further oxidation to benzoic acids. Activation of nitric acid catalyzed aerobic oxidation by the fluorinated solvent made the use of 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) or a metal catalyst superfluous. [ABSTRACT FROM AUTHOR]

Published
2017
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14. Discovery and Hit-to-Lead Optimization of Benzothiazole Scaffold-Based DNA Gyrase Inhibitors with Potent Activity against Acinetobacter baumanniiand Pseudomonas aeruginosa

Author

Cotman, Andrej Emanuel, Durcik, Martina, Benedetto Tiz, Davide, Fulgheri, Federica, Secci, Daniela, Sterle, Maša, Možina, Štefan, Skok, Žiga, Zidar, Nace, Zega, Anamarija, Ilaš, Janez, Peterlin Mašič, Lucija, Tomašič, Tihomir, Hughes, Diarmaid, Huseby, Douglas L., Cao, Sha, Garoff, Linnéa, Berruga Fernández, Talía, Giachou, Paraskevi, Crone, Lisa, Simoff, Ivailo, Svensson, Richard, Birnir, Bryndis, Korol, Sergiy V., Jin, Zhe, Vicente, Francisca, Ramos, Maria C., de la Cruz, Mercedes, Glinghammar, Björn, Lenhammar, Lena, Henderson, Sara R., Mundy, Julia E. A., Maxwell, Anthony, Stevenson, Clare E. M., Lawson, David M., Janssen, Guido V., Sterk, Geert Jan, and Kikelj, Danijel

Abstract

We have developed compounds with a promising activity against Acinetobacter baumanniiand Pseudomonas aeruginosa, which are both on the WHO priority list of antibiotic-resistant bacteria. Starting from DNA gyrase inhibitor 1, we identified compound 27, featuring a 10-fold improved aqueous solubility, a 10-fold improved inhibition of topoisomerase IV from A. baumanniiand P. aeruginosa, a 10-fold decreased inhibition of human topoisomerase IIα, and no cross-resistance to novobiocin. Cocrystal structures of 1in complex with Escherichia coliGyrB24 and (S)-27in complex with A. baumanniiGyrB23 and P. aeruginosaGyrB24 revealed their binding to the ATP-binding pocket of the GyrB subunit. In further optimization steps, solubility, plasma free fraction, and other ADME properties of 27were improved by fine-tuning of lipophilicity. In particular, analogs of 27with retained anti-Gram-negative activity and improved plasma free fraction were identified. The series was found to be nongenotoxic, nonmutagenic, devoid of mitochondrial toxicity, and possessed no ion channel liabilities.

Published
2023
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15. 3D Pharmacophore-Based Discovery of Novel K V 10.1 Inhibitors with Antiproliferative Activity.

Author

Toplak, Žan, Hendrickx, Louise Antonia, Gubič, Špela, Možina, Štefan, Žegura, Bojana, Štern, Alja, Novak, Matjaž, Shi, Xiaoyi, Peigneur, Steve, Tytgat, Jan, Tomašič, Tihomir, Pardo, Luis A., Mašič, Lucija Peterlin, and Roszik, Jason

Subjects
DRUG discovery, PHARMACOPHORE, STRUCTURAL models, ANTINEOPLASTIC agents, MEDICAL screening, APOPTOSIS, MEMBRANE glycoproteins, GENE expression, MEMBRANE transport proteins, CELL proliferation, MOLECULAR structure, PHARMACEUTICAL chemistry, CELL lines, LIGANDS (Biochemistry), CHEMICAL inhibitors
Abstract

Simple Summary: A novel structural class of inhibitors of the voltage-gated potassium channel KV10.1 was discovered by a ligand-based drug design method using a 3D pharmacophore model. The virtual screening hit compound ZVS-08 inhibited the channel in a voltage-dependent manner consistent with the action of a gating modifier. Structure–activity relationship studies revealed a nanomolar KV10.1 inhibitor that is selective for some KV and NaV channels but exhibits significant inhibition of the hERG channel. KV10.1 inhibitor 1 inhibited the growth of the MCF-7 cell line expressing high levels of KV10.1 and low levels of hERG more potently than the Panc1 cell line (no KV10.1 and high hERG expression). Moreover, the KV10.1 inhibitor 1 induced significant apoptosis in tumour spheroids of Colo-357 cells. This study may provide a basis for the use of computational drug design methods for the discovery of novel KV10.1 inhibitors as new promising anticancer drugs. (1) Background: The voltage-gated potassium channel KV10.1 (Eag1) is considered a near- universal tumour marker and represents a promising new target for the discovery of novel anticancer drugs. (2) Methods: We utilized the ligand-based drug discovery methodology using 3D pharmacophore modelling and medicinal chemistry approaches to prepare a novel structural class of KV10.1 inhibitors. Whole-cell patch clamp experiments were used to investigate potency, selectivity, kinetics and mode of inhibition. Anticancer activity was determined using 2D and 3D cell-based models. (3) Results: The virtual screening hit compound ZVS-08 discovered by 3D pharmacophore modelling exhibited an IC50 value of 3.70 µM against KV10.1 and inhibited the channel in a voltage-dependent manner consistent with the action of a gating modifier. Structural optimization resulted in the most potent KV10.1 inhibitor of the series with an IC50 value of 740 nM, which was potent on the MCF-7 cell line expressing high KV10.1 levels and low hERG levels, induced significant apoptosis in tumour spheroids of Colo-357 cells and was not mutagenic. (4) Conclusions: Computational ligand-based drug design methods can be successful in the discovery of new potent KV10.1 inhibitors. The main problem in the field of KV10.1 inhibitors remains selectivity against the hERG channel, which needs to be addressed in the future also with target-based drug design methods. [ABSTRACT FROM AUTHOR]

Published
2021
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