Group for the synthesis and biological research of organic compounds

– izv.prof. dr.sc. Mirjana Skočibušić
– izv.prof. Ines Primožič, Kemijski odsjek, PMF Zagreb

Research areas:

• Design and synthesis of heterocyclic compounds
• Biochemical analysis
• Determination of antioxidative and antimicrobial activities

Research description:

One of the biggest challenges of today mankind is the incidence of a bacterial antibiotic resistance, which is continually growing. The antibiotic resistance is posing a global threat not only for the health system, but also in the process of food production and safety. Therefore, in our laboratory we aim to design and synthesize the heterocyclic compounds, with a special interest in quaternary ammonium salts which display a wide biological potential and biomedical application (antidotes, acetylcholinesterase inhibitors, surfactants, therapeutics etc.). The synthesized compounds are further characterized by fundamental physical-chemical methods FTIR, NMR and MS, after which antimicrobial activities on different strains of fungi and bacteria (Gram positive and Gram negative pathogen species) are determined. Antioxidative activity of compounds is assessed on healthy cell lines but also by using several in vitro methods (DPPH and ORAC). Cytotoxicity of compounds is measured on healthy and tumor cell lines by MTT method.

Contacts with academic and other institutions:

– PMF Zagreb, Kemijski odsjek
– IRB Zagreb
– Institut za medicinska istraživanja i medicinu rada, Zagreb

Description of the current cooperation:

The group leader was previously engaged in the Ministry of Science, Education and Sport project under the title ‘Synthesis and enzyme transformation of biologically active compounds’ (S. Tomić-Pisarović, group leader) from 2007-2014. where she has worked on design, synthesis and characterization of organic compounds with the aim to explore their biological activity. During the collaboration with the mentioned institutions, the group leader has published several relevant scientific papers from the field of biologically active compound synthesis and their kinetic research in the interaction with enzymes and antimicrobial activity of synthesized surfactants.

Plans for future research:

The basic aim of the future research is synthesis, structural analysis of new class of heterocyclic compounds such as quinuclidinium, imidazolium, benzylimidazolium and oxazolium derivatives, which are often found as a part of compounds with a broad spectrum of biological activity. The main interest would be on the synthesis of quaternary ammonium salts mentioned derivatives which have a vast application as surfactants, antimicrobial agents and distinguished antioxidative properties. These research will be further explored on biological evaluation of all synthesized compounds, and will be performed partly in collaborative institutions with for correlation of structure with biological activity. Biological research will encompass antibacterial, antifungal and antioxidative properties. Also, cytotoxicity of all compounds will be explored because new knowledge to which our research is directed will open up the possibility of discovering new biologically active compounds with application in pharmaceutical and chemical industry, medicine, biotechnology and ecology.

List of selected research papers:

Članak u časopisima
1. Odžak, R.; Skočibušić, M.; Šprung M.; Soldo B.; Gudelj M.; Muić A.; Primožič, I. Quaternary quinuclidinium salts with different substituent at position 3: Synthesis, antimicrobial and antioxidative activities, poslan rad
2. Skočibušić, M.; Odžak, R.; Štefanić, Z.; Križić, I.; Krišto, L.; Jović, O.; Hrenar, T.; Primožič, I.; Jurašin, D. (2016). Structure-Property Relationship of Quinuclidinium Surfactants – Towards Multifunctional Biologically Active Molecules. Colloids and surfaces. B, Biointerfaces, 140 548-559.
3. Odžak, R.; Skočibušić, M.; Maravić, A. (2013). Synthesis and antimicrobial profile of N-substituted imidazolium oximes and their monoquaternary salts against multidrug resistant bacteria, Bioorganic & medicinal chemistry, 21 23; 7499-7506.
4. Odžak, R.; Čalić, M.; Hrenar, T.; Primožič, I.; Kovarik, Z. (2007). Evaluation of monoquaternary pyridinium oximes potency to reactivate tabun-inhibited human acetylcholinesterase, Toxicology, 233 1-3; 85-96.
5. Odžak, R.; Primožič, I.; Tomić, S. (2007). 3-Amidoquinuclidine Derivatives: Synthesis and Interaction with Butyrylcholinesterase, Croatica Chemica Acta, 80 1; 101-107.
6. Odžak, R.; Tomić, S. (2006). 3-Amidoquinuclidine derivatives: synthesis of compounds and inhibition of butyrylcholinesterase, Bioorganic Chemistry, 34 2; 90-98.

znanstveni i stručni rad u zborniku i zbirci radova

1. Odžak, R.; Primožič, I.; Gudelj, M.; Muić, A.; Skočibušić, M. (2016) Quaternary ammonium salts differing in the substituent at position 3 of quinuclidine ring: synthesis and antimicrobial activity. 17th Tetrahedron Symposium Challenges in Biological, Bioorganic, Organic & Medicinal Chemistry, Sitges, Španjolska Elsevier (72).
2. Odžak, R.; Skočibušić, M.; Puizina, J.; Čikeš Čulić, V.; Primožič, I. (2016) Evaluation of inhibitory effects of racemic and enantiomerically pure N-benzyl-3-amidoquinuclidinim salts against extended spectrum β-lactamase-producing pathogens. 17th Tetrahedron Symposium Challenges in Biological, Bioorganic, Organic & Medicinal Chemistry, Sitges, Španjolska Elsevier (21).
3. Primožič, I.; Skočibušić, M.; Hrenar, T.; Odžak, R. (2016) Discovery of novel imidazolium oximes as modulators for extended-spectrum β-lactamases-induced multidrug resistance in Gram-negative bacteria. 17th Tetrahedron Symposium Challenges in Biological, Bioorganic, Organic & Medicinal Chemistry, Sitges, Španjolska Elsevier (83).
4. Skočibušić, M.; Odžak, R.; Primožič, I. (2016) Quinuclidinium surfactants enhance drug activity against diverse fungal pathogens. 17th Tetrahedron Symposium Challenges in Biological, Bioorganic, Organic & Medicinal Chemistry Sitges, Španjolska Elsevier (126).
5. Tomić-Pisarović, S.; Simeon-Rudolf, V.; Odžak, R. (2007) Pyridinium, imidazolium and quinuclidinium compounds: synthesis, interaction with cholinesterases, and potential antidotes of organophosphorus compounds. IUPAC/OPCW International Workshop, The Impact of Advances in Science and Technology on the Chemical Weapons Convention, Zagreb. Book of Abstract / Škare, Danko; Bowman, Katherine; Lekić, Tamara (ur.). Zagreb : Croatian Society of Chemical Engineers (57-59).