Project for Young Researchers for 2024-2025
V. Innovative technologies, sustainable energy, digitization
- Dr. Vsevolod POGREBNOI
- Dr. Dmitri BILAN
- Sergiu COJOCARI
- Dr. Cristina GRAJDINAR (Institute of Genetics, Physiology, and Plant Protection of MSU)
- Dr. Lilia Cazacu,
- Daniil Feldman
The project is dedicated to obtaining formulations with antiviral, fungicidal and immunostimulating properties for their use in agriculture. The composition of thetargeted formulations will contain chitosan, a natural compound obtained from local sources - bee colonies, with the addition of different active substances of naturalor synthetic origin. The project will be carried out in 5 main stages and will include the synthesis of bioactive compounds, previously established by the project team(chitosan, spiro[cyclopropane-oxindoles], vinyltriazoles); preparing formulations for treating plants and establishing optimal concentrations of active substances inthem; determining the corelation between the bioactivity and the chemical structure of the compounds, and evaluating the structure of the substance with the highestpotential activity by quantum-chemical methods; synthesis of the compounds modeled by computational methods; establishing the optimal concentration of thesolutions of substances proposed for the treatment of plants. Moreover, in collaboration with the Institute of Genetics, Physiology and Plant Protection of USM,biological testing of the formulations obtained on plants will be carried out. The project will search for new and more effective drug candidates. Two strategies will beapplied to achieve this objective. First of all, formulations will be obtained with the content of the previously developed natural and synthetic products. Second, a newlibrary of mimetic derivatives will be obtained by computational prediction of the activity of new derivatives and their synthesis. Both strategies will use advancedapproaches to generate new bioactive formulations that deliver economic and social benefits. In the final stage of the announced project, the components of theformulations will be optimized to obtain the most promising ones and laboratory regulations will be developed to expand production for their use in agriculture for theprotection of plants against phytopathogens.
Summary of the activity and results obtained in 2024
The main objective of the 2024 stage of the project was to develop bioactive formulations with fungicidal and immunostimulatory properties for use in agriculture, focusing on protecting tomatoes from diseases. Specific objectives included the synthesis of triazolic and spiro[cyclopropan-oxindole] compounds, obtaining chitosan from natural sources, developing formulations with different compositions, and studying the fungicidal and growth-stimulating properties of the tested substances.
Natural sources such as champignon mushrooms and dead bees were used to obtain chitosan. Additionally, a synthetic chitosan solution was prepared for comparison. The process involved specific hydrolysis conditions in the presence of hydrochloric acid.
For the targeted synthesis of compounds with fungicidal activity, six new substances from the triazole series were synthesized and characterized using physico-chemical methods, along with four compounds from the spiro[cyclopropan-oxindole] series with antiviral potential. Four triazolic compounds with patented fungicidal properties were also sourced from the laboratory's stock for biological testing on tomatoes.
A total of 30 preparative formulations with varying concentrations and compositions of active substances were developed. These formulations included simple solutions, mixtures with chitosan, and solutions stabilized with surfactants.
Biological tests on fungicidal properties demonstrated that the tested substances were effective against Fusarium spp., with efficiency comparable to commercial preparations such as Topaz and Fitosporin. The activity was validated through qPCR analysis of the pathogen DNA.
The effects on tomato growth were also studied. It was observed that the tested substances had a stimulatory effect on root and stem growth, particularly under biotic stress conditions.
Among the most notable results obtained were: -four previously patented substances for activity against wheat fungi showed promising results against tomato fungi; -the newly synthesized substances demonstrated significant biological activity, offering prospects for their use in agricultural treatments; -both natural and synthetic chitosan exhibited fungicidal effects and proved useful in the tested formulations, including combinations with active substances; -in vitro tests confirmed the antimicrobial activity of the preparations against several species of bacteria and fungi.
The scientific impact of the project lies in the generation of new knowledge about the structure-activity relationship of bioactive compounds, contributing to the development of advanced synthesis and evaluation methodologies. The social impact involves the potential reduction of agricultural losses through the use of eco-friendly alternatives to conventional fungicides, supporting sustainability. The developed formulations provide opportunities for producing innovative commercial products, reducing treatment costs and losses caused by pathogens.
Challenges encountered included delays in reagent delivery, which limited the variation possibilities of the synthesized substances.
Summary of the activity and results obtained in 2025
The project “Development of formulations against tomato phytopathogens based on autochthonous natural substances and their derivatives” aimed to design effective and environmentally friendly bioactive formulations for the protection of tomato plants against phytopathogens, with a particular focus on fungal agents of the genus Fusarium, using natural chitosan and synthetic derivatives with proven biological activity. Within the framework of the project, new compounds from the spiro[cyclopropane-oxindole] series with antiviral potential and triazole derivatives with antifungal activity were synthesized and structurally characterized.
Quantum-chemical studies enabled the establishment of structure–biological activity relationships, and the obtained results were further used for the rational design and targetedsynthesis of new compounds with enhanced efficacy. In total, more than 30 triazole derivatives were synthesized, several of which are novel and previously unreported in the literature. Over 100 preparative formulations were developed, containing different concentrations of the active
substances, both alone and in combination with chitosan. In vitro biological evaluations demonstrated that the majority of the tested formulations stimulate root system development and exhibit significant antifungal activity against Fusarium spp. Several compounds showed efficacy comparable to or exceeding that of commercial reference products (Topaz and Fitosporin), even at very low active substance concentrations (0.01% and 0.0002%). A synergistic effect between certain triazole derivatives and chitosan was observed, and it was established that the chemical structure of the compounds has a more pronounced impact on plant metabolism than either concentration or the presence of chitosan.
The antifungal activity was further confirmed using modern molecular techniques (qPCR), demonstrating high efficiency and specificity in the quantification of pathogen DNA. Field trials confirmed the practical potential of several formulations, some of which inhibited Fusarium propagation more effectively than the commercial fungicides used as references.
The project results were disseminated through oral presentations and posters at national and international scientific conferences, as well as through participation in invention exhibitions, where gold and silver medals were awarded. Based on the obtained results, four patent applications were submitted to AGEPI, and a bilateral Republic of Moldova–Turkey project (TUBITAK program 2026–2028) was initiated, focusing on the development and application of innovative formulations for crop protection.
Overall, the project demonstrates significant scientific, social, and economic impact, providing a solid foundation for the development of efficient and sustainable alternatives to conventional fungicides, with strong potential for technological transfer and practical implementation in agriculture.
Articles in Web of Science și SCOPUS journals
- SUCMAN, N., BILAN, D., MACAEV, F. Double cross-aldol condensation of isatins with acetone.ChemJMold, 2026, 21(1) submitted (IF 0.5) http://cjm.ichem.md/manuscripts-in-progress
Abstracts
- SUCMAN, N., GORINCIOI, E., POGREBNOI, V., ROTARU, A., MACAEV, F. Antiproliferative and DNA-interacting properties of 6-(2,4-dichlorobenzoyl)-7-(2,4-dichlorophenyl)indolo[3,4-jk]phenanthridin-5(4H)-one. În: Book of abstracts INnovative ThERApeutiC Targets In nOn-canonical Nucleic acids structures Winter InterNational School2025 INTERACTION WINS 2025, 24-28 februarie 2025, Pavia, Italy, p.69
- SUCMAN N., GRAJDIERU C., POGREBNOI V., COJOCARI S., CAZACU L. Investigation of immunostimulatory effects of triazole-based preparative forms on tomato seeds germinated in Fusarium spp.-contaminated soil. În materiale conferinței MEDICINA, ȘTIINȚELE MOLECULARE ȘI DE MEDIU 2025 MedMolMed 2025, 10-15 November 2025, Chișinău, Republica Moldova, p. 70.
- GRAJDIERU Cristina, SUCMAN Natalia, POGREBNOI Vsevolod, COJOCARI Sergiu. Novel trizole derivates and chitosan reveal synergy in suppressing Fusarium spp. In: Simpozionul științific international ”Biotehnologii avansate – relizări și perspective”, Ed. 7, 15-17 septembrie 2025, Editura USM, 2025, pp. 147-148. ISBN 978-9975-62-907-2
- SUCMAN, N., POGREBNOI, V., POGREBNOI, S., COJOCARI, S., GRAJDIERU, K., LUPASCU, L., MACAEV. F. Sinteza și caracterizarea derivaților de triazol cu proprietăți fungicide pentru aplicații în medicină și agricultură. În: Al X-lea congres al farmaciștilor din Republica Moldova cu participare internațională, 22 noiembrie 2024, Rezumate, , p. 69-71.https://drive.google.com/file/d/1QVHD460TGa9zZSH1Q_gu581f6v0mHWZE/view
Patents
- CEABANOVA M., GRAJDIERU C., SUCMAN N., POGREBNOI V., COJOCARI S, MITINA I., MITIN V., POGREBNOI S., MACAEV F. Utilizarea 2-(tert-butyl)-6-chloro-3-(1H-1,2,4-triazol-1-il)-2H-chromen-2-olului ca agent imunostimulator și antifungic împotriva Fusarium spp. în tratamentul semințelor de tomate. Cerere brevet nr. 7502, dată înregistrare 05.05.2025. Nr. depozit: a 2025 0023.
- SUCMAN Natalia, (MD); GRAJDIERU Cristina, (MD); POGREBNOI Vsevolod, (MD); COJOCARI Sergiu, (MD); MITINA Irina, (MD); MITIN Valentin, (MD); POGREBNOI Serghei, (MD); MACAEV Fliur, (MD). Utilizarea 1-((4-propil-2-(p-tolil)-1,3-dioxolan-2-il)metil)-1H-1,2,4-triazolului ca agent imunostimulator și antifungic împotriva Fusarium spp. în tratamentul semințelor de tomate. Cerere brevet nr. 7525, dată înregistrare 19.06.2025. Nr. depozit: a 2025 0032.
- SUCMAN Natalia, MD; GRAJDIERU Cristina, MD; POGREBNOIVsevolod, MD; COJOCARI Sergiu, MD; MITINA Irina, MD; MITIN Valentin, MD; POGREBNOI Serghei, MD; ARÎCU Aculina, MD; MACAEV Fliur, MD. Forma preparativă pe bază de bromură de 4-(2-(4-metoxifenil)-2-oxoetil)-1-(2-oxo-2-(p-tolil)etil)-1H-1,2,4-triazol-4-iu, cu acţiune antifungică împotriva Fusarium spp., destinată tratamentului seminţelor de tomate. Cerere brevet nr. 7554, dată înregistrare 21.08.2025. Nr. depozit: a 2025 0038.
- SUCMAN Natalia, MD; GRAJDIERU Cristina, MD; POGREBNOI Vsevolod, MD; COJOCARI Sergiu, MD; MITINA Irina, MD; MITIN Valentin, MD; POGREBNOI Serghei, MD; ARÎCU Aculina, MD; MACAEV Fliur, MD. Utilizarea clorurei de 1-(2-oxo-2-(ptolil)etil)-1H-1,2,4-triazol-4-iu ca agent imunostimulator şi antifungic împotriva Fusarium spp. în tratamentul seminţelor de tomate. Cerere brevet nr. 7555, dată înregistrare 21.08.2025. Nr. depozit: a 2025 0039.