Pristupačnost
NAZIV PROJEKTA / PROJECT TITLE: Mikroorganizmi kao izvor novih klasa antibiotika – Od totalne sinteze do novog kemijskog prostora i metodologije / Microorganisms as source of new antibiotics - From total synthesis to new chemical space and methodology
Trajanje / Duration: 01.06.2025. – 31.05.2028.
Financiranje / Funding: Hrvatska zaklada za znanost / Croatian Science Foundation
VODITELJ PROJEKTA / PRINCIPAL INVESTIGATOR: izv. prof. dr. sc. Nikola Cindro
INSTITUCIJE KOJE SUDJELUJU U PROJEKTU / INSTITUTIONS:
Prirodoslovno-matematički fakultet Sveučilišta u Zagrebu / Faculty of Science at University of Zagreb (UniZg)
Sveučilište u Rijeci, Fakultet biotehnologije i razvoja lijekova, Hrvatska / University of Rijeka, Faculty of Biotechnology and Drug Development, Croatia (UniRi)
Institut Ruđer Bošković / Ruđer Bošković Institute
SAŽETAK:
Antimikrobna rezistencija predstavlja značajan problem u globalnom zdravstvenom sustavu. Jedno od rješenja je razvoj novih sintetskih analoga već postojećih klasa antibiotika, međutim bakterije puno lakše modificiraju svoje mehanizme rezistencije na takvim spojevima. Dugoročnije rješenje ovoga problema nalazimo u razvoju novih klasa antimikrobnih spojeva.
U sklopu ovog projekta bit će po prvi puta sintetizirani predstavnici triju klasa spojeva koji su prethodno izolirani iz prirodnog materijala, strukturno okarakterizirani, te im je in vitro određena značajna antimikrobna aktivnost, pogotovo za neke rezistentne bakterijske sojeve. Na sintetiziranim spojevima provest će se antimikrobna ispitivanja kako bi se potvrdila njihova aktivnost na širem bakterijskom panelu. Tri klase nedavno otkrivenih spojeva koje će biti obuhvaćene ovim projektom su:a) Enceleamicinib) Modificirani Cihunamidic) Kalofikolidi i bromofikolidiPrilikom razvoja sintetskih pristupa za pojedine klase spojeva također će se razvijati i nova sintetska metodologija za određeni strukturni motiv te klase, u svrhu razvoja robusnog pristupa problematičnim strukturnim fragmentima. Neke od metodologija koje će se razvijati su dupla Grignardova reakcija bazirana na adiciji različitih organometalnih reagensa i mehanokemijska ciklizacija oligopeptida. Osim toga planira se i sinteza strukturnih analoga u svakoj od navedenih skupina kako bi se provela SAR (Structure-Activity Relationship) istraživanja na navedenim klasama spojeva.
ABSTRACT:
Antimicrobial resistance poses a significant problem in the global healthcare system. One solution is the development of new synthetic analogs of existing classes of antibiotics; however, bacteria can more easily modify their resistance mechanisms to such compounds. A longer-term solution to this problem lies in the development of new classes of antimicrobial compounds.
As part of this project, representatives of three classes of compounds, previously isolated from natural sources, structurally characterized, and showing significant in vitro antimicrobial activity, especially against some resistant bacterial strains, will be synthesized for the first time. Antimicrobial testing will be conducted on the synthesized compounds to confirm their activity on a broader bacterial panel. The three classes of recently discovered compounds to be included in this project are:a) Enceleamycinsb) Modified Cihunamidesc) Callophycoic and Bromophycoic acidsDuring the development of synthetic approaches for individual classes of compounds, new synthetic methodology will also be developed for specific structural motifs of that class, aiming to develop a robust approach to problematic structural fragments. Some of the methodologies to be developed include double Grignard reactions based on the addition of various organometallic reagents to lactones and mechanochemical cyclization reactions of oligopeptides. Additionally, the synthesis of structural analogs in each of the mentioned groups is planned to enable SAR (Structure-Activity Relationship) studies on these classes of compounds.
PROJEKTNI TIM / PROJECT TEAM:
Znanstveni radovi / Publications:
1. Duvnjak, Mirko; Talajić, Gregor; Baranašić, Jurica; Baus Topić, Nea; Čipčić Paljetak, Hana; Cindro, Nikola, Total Synthesis of (+)-Penicyclone A and Evaluation of Biological Activity Including Intermediate Compounds, Int. J. Mol. Sci. 2025, 26(14), 6643, doi: https://doi.org/10.3390/ijms26146643
Sudjelovanje na skupovima / Conference participation:
1. Martin Husinec, Jana Hrnjak, Marija Alešković, Nikola Cindro, Diastereoselective Synthesis of Chiral Tertiary Alcohols via Sequential Grignard Addition to Lactones, 29th Croatian Meeting of Chemists and Chemical Engineers, Split, Croatia, September 2–5, 2025 (poster).
2. Nikolina Vidović, Karla Selar, Rafaela Šilje, Nikola Cindro, Matija Modrušan, Gordan Horvat, and Vladislav Tomišić, Efficient Cyclization of Functionalized Peptides via Chloride Templating, 29th Croatian Meeting of Chemists and Chemical Engineers, Split, Croatia, September 2–5, 2025 (poster).
3. Nikola Cindro, Mirko Duvnjak, Nikolina Vidović, Krunoslav Užarević, Gordan Horvat, Vladislav Tomišić, Giovanna Speranza, Mechanochemical anion-templated synthesis of cyclopeptides, Adriatic NMR Conference, Vodice, Croatia, September 17–20, 2025 (pozvano predavanje).