Naziv projekta: Otkriće i razvoj novih biološki aktivnih kvaternih amonijevih spojeva derivata kinuklidina

Trajanje: 1. veljače 2021. – 31. siječnja 2026.

Voditeljica: izv. prof. dr. sc. Matilda Šprung

Sažetak ključnih pokazatelja

Pokazatelj Broj
Znanstveni radovi u časopisima 9 (planirano 4 — premašeno preko dvostruko)
Priopćenja na skupovima 25
— od toga pozvana predavanja 4
— od toga posterske prezentacije 21
Obranjene doktorske disertacije 2
Mentorirani završni radovi 6
Mentorirani diplomski radovi 2
Znanstvene institucije-suradnici 4
Pohađane radionice/škole tima 7

 

1. Znanstveni radovi u časopisima (9)

  1. Crnčević D, Krce L, Mastelić L, Maravić A, Soldo B, Aviani I, Primožić I, Odžak R, Šprung M. The mode of antibacterial action of quaternary N-benzylimidazole salts against emerging opportunistic pathogens. Bioorganic Chemistry. 2021;112:104938. doi: 10.1016/j.bioorg.2021.104938
  2. Crnčević D, Krce L, Cvitković M, Brkljača Z, Sabljić A, Vuko E, Primožić I, Odžak R, Šprung M. New Membrane Active Antibacterial and Antiviral Amphiphiles Derived from Heterocyclic Backbone of Pyridinium-4-Aldoxime. Pharmaceuticals. 2022;15:775. doi: 10.3390/ph15070775
  3. Odžak R, Crnčević D, Sabljić A, Primožić I, Šprung M. Synthesis and Biological Evaluation of 3-Amidoquinuclidine Quaternary Ammonium Compounds as New Soft Antibacterial Agents. Pharmaceuticals. 2023;16:187. doi: 10.3390/ph16020187
  4. Odžak R, Crnčević D, Sabljić A, Krce L, Paladin A, Primožić I, Šprung M. Further Study of the Polar Group’s Influence on the Antibacterial Activity of the 3-Substituted Quinuclidine Salts with Long Alkyl Chains. Antibiotics. 2023;12:1231. doi: 10.3390/antibiotics12081231
  5. Crnčević D, Ramić A, Radman Kastelic A, Odžak R, Krce L, Weber I, Primožić I, Šprung M. Naturally derived 3-aminoquinuclidine salts as new promising therapeutic agents. Scientific Reports. 2024;14:26211. doi: 10.1038/s41598-024-77647-5
  6. Crnčević D, Krce L, Brkljača Z, Cvitković M, Babić Brčić S, Čož-Rakovac R, Odžak R, Šprung M. A dual antibacterial action of soft quaternary ammonium compounds: bacteriostatic effects, membrane integrity, and reduced in vitro and in vivo toxicity. RSC Advances. 2025;15:1490–1506. doi: 10.1039/d4ra07975b
  7. Crnčević D, Odžak R, Šprung M. A Short Review on Quaternary Ammonium Compounds (QACs): From Antibacterial Action to Next-Generation Design. Croatica Chemica Acta. 2025;98(2). doi: 10.5562/cca4169
  8. Sabljić A, Čarija D, Ramić A, Šprung M, Odžak R. Structure–Function Insights into Quinuclidine-3-One BisQACs: Synthesis, Modulation of Bacterial Resistance, Structure–Activity Relationship, and Biological Profiling. Pharmaceuticals. 2025;18:1286. doi: 10.3390/ph18091286
  9. Sabljić A, Čarija D, Begić K, Odžak R, Čož-Rakovac R, Tomaš J, Šprung M. Quinuclidin-3-one-based quaternary ammonium compounds as potent antibacterials against Staphylococcus aureus and Listeria monocytogenes. Biomolecules and Biomedicine. 2026. doi: 10.17305/bb.2026.14037

2. Pozvana predavanja (4)

  1. Čarija, D.; Sabljić, A.; Odžak, R.; Krce, L.; Šprung, M. Quinuclidine-based quaternary ammonium compounds: A natural scaffold for antimicrobial innovation. FEBS3+ Meeting: Advances in Molecular Biosciences. Belgrade, 2025. str. 47.
  2. Šprung, M. New generation of quaternary ammonium compounds: the potent amphiphiles in combating bacterial resistance. Solutions in Chemistry 2024. Zagreb: Hrvatsko kemijsko društvo, 2024. str. 26.
  3. Crnčević, D.; Krce, L.; Odžak, R.; Šprung, M. Probing the membranolytic activity of novel quaternary ammonium compounds using atomic force microscopy. 2nd Croatian Microscopy Symposium. Split, 2023. str. 12–13.
  4. Mastelić, L.; Maravić, A.; Krce, L.; Soldo, B.; Odžak, R.; Bučević Popović, V.; Aviani, I.; Primožič, I.; Šprung, M. New antimicrobial candidates – quaternary ammonium compounds based on natural scaffold quinuclidine. FEBS Open Bio, 11, S1 (2021), str. 101–102.

3. Posterske prezentacije (21)

  1. Čarija, D.; Odžak, R.; Šprung, M. Quinuclidine-based soft quaternary ammonium compounds: toward safer and environmentally conscious antimicrobial agents. EFMC-ASMC 2025. Porto, 2025. str. 366.
  2. Krce, L.; Čarija, D.; Šprung, M. Elucidating the antibacterial mode of action of soft amidoquinuclidine-based QACs through AFM and biophysical analysis. EFMC-ASMC 2025. Porto, 2025. str. 190.
  3. Čarija, D.; Sabljić, A.; Odžak, R.; Krce, L.; Šprung, M. Quinuclidine-based quaternary ammonium compounds: A natural scaffold for antimicrobial innovation. FEBS3+ Meeting: Exploring Molecular Frontiers. Zagreb: HDBMB, 2024. str. 47.
  4. Odžak, R.; Sabljić, A.; Šprung, M. Quinuclidine BisQACs: structure–activity relationship analysis with focus on antimicrobial resistance. 29th Croatian Meeting of Chemists and Chemical Engineers / 7th Symposium Vladimir Prelog. Split, 2025. str. 165.
  5. Sabljić, A.; Šprung, M.; Odžak, R. Design and synthesis of soft quaternary ammonium salts based on 3-aminoquinuclidine with amide-linked alkyl chains. 29th Croatian Meeting of Chemists and Chemical Engineers / 7th Symposium Vladimir Prelog. Split, 2025. str. 181.
  6. Crnčević, D.; Odžak, R.; Šprung, M. Exploring enzymatic pathways for degradation of eco-friendly 3-amidoquinuclidine QACs. Solutions in Chemistry 2024. Zagreb, 2024. str. 59.
  7. Crnčević, D.; Krce, L.; Odžak, R.; Šprung, M. New perspective 3-amidoquinuclidine QACs: Bacteriostatic mode of action and inhibition of protein synthesis pathways. EFMC-ISMC. Rim, 2024. str. 275.
  8. Odžak, R.; Crnčević, D.; Šprung, M. New monoquaternary ammonium surfactants and their permeability through modeled biomembrane. Solutions in Chemistry 2024. Zagreb, 2024. str. 89.
  9. Crnčević, D.; Primožič, I.; Krce, L.; Šprung, M.; Odžak, R. 3-aminoquinuclidine quaternary salts – new generation of potent antibacterial agents. EFMC-ISMC. 2024. str. 359.
  10. Odžak, R.; Sabljić, A.; Šprung, M. Quaternary 3-Quinuclidinone Compounds: Potent Antibacterial Agents Against Staphylococcus aureus and Listeria monocytogenes. 27th Congress of SCTM. Skoplje, 2024. str. 141.
  11. Sabljić, A.; Šprung, M.; Odžak, R. Natural Derived Mono- and bisQACs from Quinuclidine Backbone as an Alternative to Commercial Disinfectants. 2nd Workshop on Mass Spectrometry in Life Sciences. Zagreb, 2024. str. 42.
  12. Sabljić, A.; Crnčević, D.; Šprung, M.; Odžak, R. The influence of amide group addition on the bioactivity of new soft 3-amidoquinuclidine QACs. 28th Croatian Meeting of Chemists and Chemical Engineers. Zagreb, 2023. str. 122.
  13. Šprung, M.; Crnčević, D.; Sabljić, A.; Odžak, R. New insights into quaternary ammonium compounds: from structure-activity optimization to antibacterial mode of action. IX EFMC-ASMC. Louvain-la-Neuve, 2023. str. 313.
  14. Crnčević, D.; Sabljić, A.; Odžak, R.; Šprung, M. Biological activity of novel environmentally compatible 3-amidoquinuclidine quaternary ammonium compounds. IX EFMC-ASMC. Louvain-la-Neuve, 2023. str. 140.
  15. Sabljić, A.; Crnčević, D.; Šprung, M.; Odžak, R. Biological evaluation of 3-aminoquinuclidine QACs with long alkyl chains as new potent antimicrobial agents. IX EFMC-ASMC. Louvain-la-Neuve, 2023. str. 298.
  16. Crnčević, D.; Sabljić, A.; Krce, L.; Primožič, I.; Odžak, R.; Šprung, M. Amidoquinuclidine salts with potent activity against Listeria monocytogenes. EFMC-ISMC 2022. Nica, 2022. str. 219.
  17. Sabljić, A.; Crnčević, D.; Šprung, M.; Odžak, R. Synthesis and antibacterial activity of 3-aminoquinuclidine quaternary ammonium salts. 6th Mini Symposium of Section of Medicinal and Pharmaceutical Chemistry. Zagreb, 2022. str. 5.
  18. Crnčević, D.; Krce, L.; Cvitković, M.; Sabljić, A.; Primožič, I.; Odžak, R.; Šprung, M. New membrane active antimicrobial amphiphiles derived from heterocyclic backbone of pyridinium-4-aldoxime. EFMC-ISMC 2022. Nica, 2022. str. 220.
  19. Bilandžić, K.; Odžak, R.; Šprung, M. Biological activity of 3-aminoquinuclidine quaternary salt. Zagreb: HKD, 2022. str. 85.
  20. Crnčević, D.; Odžak, R.; Šprung, M. Amido-quinuclidine based QACs as a new soft antimicrobial agents susceptible to protease degradation. 2021. str. 420.
  21. Crnčević, D.; Sabljić, A.; Odžak, R.; Šprung, M. Synthesis and antibacterial activities of new amidoquinuclidines and their quaternary salts. 2021. str. 11.

4. Doktorske disertacije proizašle iz projekta (2)

  1. Doris Čarija (Crnčević) — Struktura, biološka aktivnost i mehanizam djelovanja novosintetiziranih kvaternih amonijevih spojeva (obranjena 14. ožujka 2025.)
  2. Antonio Sabljić — Sinteza i biološka aktivnost mono- i biskvaternih amonijevih spojeva na okosnici 1-azabiciklo[2.2.2]oktana (obranjena 8. prosinca 2025.)

5. Mentorirani ocjenski radovi studenata (8)

Sveučilišni završni radovi (6)

  1. Nakić Terzić, Lara Marie — Toksičnost kvaternih amonijevih spojeva, PMF Split, 2026.
  2. Selak, Branimir — Mehanizmi bakterijske rezistencije prema kvaternim amonijevim spojevima, PMF Split, 2025.
  3. Močić, Matea — Antimikrobna aktivnost kvaternih fosfonijevih spojeva, PMF Split, 2024.
  4. Žilić, Žana — Biološka aktivnost kvaternih amonijevih spojeva, PMF Split, 2024.
  5. Bilandžić, Katijana — Biološka aktivnost kvarterne soli 3-aminokinuklidina, Split, 2022.
  6. Ćurić, Lucijana — Komercijalne kvaterne amonijeve soli – potencijalni supstrati Qac efluks pumpi, PMF Split, 2022.

Sveučilišni diplomski radovi (2)

  1. Vitovski, Mihaela — Oligomerizacijsko stanje transkripcijskog regulatora QacR iz bakterije Staphylococcus aureus, PMF Split, 2023.
  2. Vidaković, Josip — Heterologna ekspresija i pročišćavanje transkripcijskog faktora QacR iz bakterije Escherichia coli, PMF Split, 2021.

6. Znanstvene suradnje

  1. PMF Sveučilišta u Zagrebu – Kemijski odsjek (dr. sc. Ines Primožić, dr. sc. Alma Ramić, dr. sc. Andreja Radman Kastelic) — dizajn, sinteza i NMR/strukturna karakterizacija kinuklidinskih derivata
  2. Institut Ruđer Bošković, Zagreb (dr. sc. Rozelindra Čož-Rakovac, dr. sc. Sanja Babić Brčić, dr. sc. Karolina Begić) — biotehnologija u akvakulturi, kemija materijala
  3. Selvita Ltd., Zagreb (dr. sc. Zlatko Brkljača) — računalne simulacije i molekularna dinamika
  4. Odjel za fiziku, PMF Split (dr. sc. Lucija Krce, dr. sc. Mislav Cvitković) — AFM, SEM, fluorescencijske i računalne analize

7. Usavršavanja članova projektnog tima

  1. Introduction to mass spectrometry in biomedical research — PMF, Split, 2023.
  2. LC/MS analysis of proteins — BIOcentar, Zagreb, 2023.
  3. Monolith User Training — NanoTemper Technologies GmbH, München, 2023.
  4. Flow Cytometry Education: From first principles to polychromatic applications — MEFST, Split, 2022.
  5. MedILS Summer School in Bioinformatics — Mediteranski institut za istraživanje života, Split, 2022.
  6. MedILS Summer School in Science Communication — Mediteranski institut za istraživanje života, Split, 2022.
  7. European School of Medicinal Chemistry — 41st Advanced Course of Medicinal Chemistry and “E. Duranti” Seminar for PhD students — Urbino, Italija, 2022.

ACTIVITES

1.) LECTURES

  • 5th Mini Symposium of Section of Medicinal and Pharmaceutical Chemistry

Synthesis and antibacterial activities of new amidoquinuclidines and their quaternary salts

Book of abstracts

  • 45th FEBS Congress, Molecules of Life: Towards New horizons, FEBS 2021

New antimicrobial candidates – quaternary ammonium compounds based on natural scaffold quinuclidine

Book of abstracts

  • The Science Festival, Split, 2021

Disinfection agents and SARS-CoV-2 virus

 

  • 6th Mini Symposium of Section of Medicinal and Pharmaceutical Chemistry, 2022 

Synthesis and Antibacterial Activity of 3- Aminoquinuclidine Quaternary Ammonium Salts 

 

  • 2nd Croatian Microscopy Symposium, 2023 

Probing the membranolytic activity of novel quaternary ammonium compounds using atomic force microscopy 

  • Solutions in Chemistry, 2024

New generation of quaternary ammonium compounds: The potent amphiphiles in combating bacterial resistance

2.) CONFERENCES WITH POSTER PRESENTATIONS

  • 27th Croatian Meeting of Chemists and Chemical Engineers

Book of abstracts

  • 26th EFMC International Symposium on Medicinal Chemistry, EFMC-ISMC 2021

Book of abstracts

 

  • 27th EFMC International Symposium on Medicinal Chemistry, EFMC-ISMC 2022

 

  • 28th Croatian Meeting of Chemists and Chemical Engineers 2023

 

  • 9th EFMC International Symposium on Advances in Synthetic and Medicinal Chemistry 202

 

  • 2nd Workshop on Mass Spectrometry in Life Sciences 2024

Book of abstracts (https://msworkshop.chem.pmf.unizg.hr/Book_of_Abstracts_2nd_Workshop_on_MS_in_LS.pdf )

  • Solutions in Chemistry 2024

Book of abstracts (https://solutionsinchemistry.hkd.hr/sic_boa/ )

 

3.) WORKSHOPS

  • European School of Medicinal Chemistry – 41st Advanced Course of Medicinal Chemistry and “E. Duranti” Seminar for PhD students 2022
  • Intenzivni tečaj iz protočne citometrije 2022. – Medicinski Fakultet u Splitu 2022
  • MedILS Summer School in Science Communication 2022
  • MedILS Summer School in Bioinformatics 2022
  • Flow Cytometry Education: From first principles to polychromatic applications 2022
  • Monolith User Training 2023
  • LC/MS analysis of proteins 2023
  • Introduction to mass spectrometry in biomedical research, 2023 – organized within the framework of the QACBioAct project
  • Crnčević, Doris; Krce, Lucija; Mastelić, Linda; Maravić, Ana; Soldo, Barbara; Aviani, Ivica; Primožič, Ines; Odžak, Renata; Šprung, Matilda The mode of antibacterial action of quaternary N- benzylimidazole salts against emerging opportunistic pathogens // Bioorganic chemistry, 112 (2021), 104938, 8 doi:10.1016/j.bioorg.2021.104938
  • Crnčević, Doris; Krce, Lucija; Cvitković, Mislav; Brkljača, Zlatko; Sabljić, Antonio; Vuko, Elma; Primožič, Ines; Odžak, Renata; Šprung, Matilda New membrane-active antibacterial and antiviral amphiphiles derived from heterocyclic backbone of pyridinium-4-aldoxime // Pharmaceuticals, 15 (2022), 7; 775, 21doi:10.3390/ph15070775
  • Odžak, Renata;  Crnčević, Doris;  Sabljić, Antonio,  Primožič, Ines; Šprung, Matilda   Synthesis and biological evaluation of 3-amidoquinuclidine quaternary ammonium compounds as new soft antibacterial agents // Pharmaceuticals, 16 (2023), 2; 187 doi: 10.3390/ph16020187 
  • Odžak, Renata; Crnčević, Doris; Sabljić, Antonio; Krce, Lucija; Paladin, Antonela; Primožič, Ines; Šprung, Matilda  , Further study of the polar group’s influence on the antibacterial activity of the 3-substituted quinuclidine salts with long alkyl chains // Antibiotics, 12 (2023), 8; 1231 doi:10.3390/antibiotics12081231
  • Crnčević, Doris; Ramić, Alma; Radman Kastelic, Andreja; Odžak, Renata; Krce, Lucija; Weber, Ivana; Primožič, Ines; Šprung, Matilda
    Naturally derived 3-aminoquinuclidine salts as new promising therapeutic agents // Scientific reports, 14 (2024), 26211, 18. doi: 10.1038/s41598-024-77647-5
  • Crnčević, Doris; Krce, Lucija, Brkljača, Zlatko; Cvitković, Mislav; Babić Brčić, Sanja; Čož-Rakovac, Rozelindra, Odžak, Renata and Šprung, Matilda A dual antibacterial action of soft quaternary ammonium compounds: Bacteriostatic effects, membrane integrity, and reduced in vitro and in vivo toxicity, RSC Advances, 2025, 15, 1490 – 1506. doi: 10.1039/d4ra07975b

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