3.1.3. Биологичноактивни молекули – дизайн, синтез, екстракция и изследване

Водещ изследовател: Проф. д-р инж. Данчо Даналев, Проф. д-р инж. Петър Тодоров

Тематика: Пептиди и хибридни хетероциклични пептидни молекули с потенциални приложения в медицината; Получаване и пречистване на биологичноактивни вещества от медицински и ароматни растения с помощта на мембранно разделяне.

Научната група включва няколко основни области на проучвания, с конкретни изследователски намерения за период от 4 години /2023-2026/:

• Пептидомиметици и биоконюгати с потенциално приложение в медицината, особено за лечение на заболявания като рак, хронична и остра болка, възпаление, бактериални инфекции:

– дизайн, синтез и изследване на биологичната активност in vitro и in vivo на новосинтезирани пептиди, техните метални комплекси с биогенни метали, хетероциклични съединения и хибридни хетероциклични пептидни молекули с противоракови, антимикробни и някои други важни фармакологични дейности чрез включване на неестествени аминокиселини в тяхната структура, с цел подобряване на фармакодинамиката им, търсене на синергичен ефект между пептидния фрагмент и допълнителния фармакофор;

– изследване на редокс поведението на новосинтезирани N-модифицирани аналози на хеморфин в различни електролитни среди (pH 1.2–12.8) чрез прилагане на волтаметрични техники. Изследване на различни биологични активности на новосинтезирани хеморфинови аналози.

– синтез и изследване на свойствата на нови аминокиселинни био-сърфактанти като носители на биологично-активни агенти.

– изследвания върху разширяване на възможностите за ефективно оползотворяване на отпадъчните продукти при производството на етерични масла от ароматни растения и билки с помощта на наномембранно разделяне. Разработване на обратноосмотични и нанофилтрационни мембрани с повишена устойчивост на запушване от биологичноактивните компоненти на медицински и ароматни растения. Разработване на високо интензивен мембранен модул с подобрени характеристики.

• Получаване и пречистване на биологичноактивни вещества от медицински и ароматни растения с помощта на мембранно разделяне.

Публикации:

1. Sirine Jaber, Veronica Nemska, Ivan Iliev, Elena Ivanova, Tsvetelina Foteva, Nelly Georgieva, Ivan Givechev, Dimiter Tanev, Emilia Naydenova, Dancho Danalev, Synthesis, antiproliferative and antimicrobial activities of (KLAKLAK)₂-NH₂ analogue containing nor-Leu and its conjugates with a second pharmacophore, Biotechnology & Biotechnological Equipment, 2023, 151-158, https://doi.org/10.1080/13102818.2022.2162965 (i.f. 1.7, Q4)
2. Dancho Danalev, Ivan Iliev, Stefan Dobrev, Silvia Angelova, Stoiko Petrin, Tatyana Dzimbova, Elena Ivanova, Dessislava Borisova, Emilia Naydenova, Synthesis, antiproliferative effect and in silico logP prediction of BIM-23052 analogs containing Tyr instead of Phe, Pharmaceutics, 2023, https://doi.org/10.3390/pharmaceutics15041123 (i.f. 5.5, Q1)
3. Boryana Borisova, Hristina Nocheva, Stéphane Gérard, Marie Cochard, Stefan Dobrev, Silvia Angelova, Stoyko Petrin, Dancho Danalev, Synthesis, In Silico LogP Study, and In Vivo Analgesic Activity of Analogs of Tetrapeptide FELL, Pharmaceuticals, 2023, 16(8), 1183; https://doi.org/10.3390/ph16081183 (i.f. 4.6, Q1)
4. Todorov, P.; Assenov, B.; Angelov, D.; Dzhambazova, E.; Pechlivanova, D. Behavioral Effects and Analgesic Profile of Hemoglobin-Derived Valorphin and Its Synthetic Analog in Rodents. Biomedicines 2023, 11, 2783. https://doi.org/10.3390/biomedicines11102783, (i.f. 4.1, Q1).
5. Todorov P, Georgieva S, Peneva P, Nikolov S, Rangelov M, Todorova N, Pechlivanova D, Tchekalarova J. Synthesis, molecular docking, electrochemical and fluorimetric analysis of new caffeic and cinnamic acid-conjugated hemorphin derivatives designed as potential anticonvulsant and antinociceptive agents. Bioorg Chem., 2024 Feb; 143:107063. https://doi.org/10.1016/j.bioorg.2023.107063 (i.f. 5.1, Q1)
6. Todorov P, Georgieva S, Tchekalarova J, Peneva P, Mateeva P, Assenov B, Dzhambazova E, Pechlivanova D. Synthesis, characterization and evaluation of anti-hyperalgesia, anticonvulsant and antioxidant activity of novel VV-hemorphin-5 analogs, Archiv der Pharmazie. 2023:e202300267. https://doi.org/10.1002/ardp.202300267 (i.f. 5.1, Q2)
7. Kameliya Anichina, Nikolai Georgiev, Nikolay Lumov, Dimitar Vuchev, Galya Popova-Daskalova, Georgi Momekov, Emiliya Cherneva, Rositsa Mihaylova, Anelia Mavrova, Stela Atanasova-Vladimirova, Iskra Piroeva, Denitsa Yancheva, Fused Triazino-benzimidazoles Bearing Heterocyclic Moiety: Synthesis, Structure Investigations, In silico and In vitro Biological activity, Molecules, 2023, 28, 5034, https://doi.org/10.3390/molecules28135034 (i.f. 4.6, Q2)
8. Boryana Borisova, Stanislava Vladimirova, Hristina Nocheva, Marie Laronze-Cochard, Stéphane Gérard, Stoyko Petrin, Dancho Danalev, Synthesis, Hydrolytic Stability and In Vivo Biological Study of Bioconjugates of the Tetrapeptides FELL Containing Pyrrole Moiety, Biomedicines, 2023, 11(12), 3265, https://doi.org/10.3390/biomedicines11123265 (i.f. 4.9, Q1)
9. K. Anichina, N. Georgiev, Synthesis of 2-Substituted Benzimidazole Derivatives as a Platform for Development of UV Filters and Radical Scavengers in Sunscreens, Organics, 2023, 4 (4), 524-538 https://doi.org/10.3390/org4040036 (i.f. 1.5, Q3).
10. P. Todorov, S. Georgieva, C. Trapella, K. Chakarov, J. Tchekalarova, D. Pechlivanova, D. Cheshmedzhieva, A. Fantinati, D. Illuminati, Synthesis, characterization, and biological study of new synthetic opioid hemorphin-4 peptides containing sterically restricted nonnatural amino acids, Arch. Pharm., 2024, e2400052. https://doi.org/10.1002/ardp.202400052 (i.f. 5.1, Q2)
11. Kameliya Anichina, Nikolay Kaloyanov, Diana Zasheva, Rusi Rusew, Rositsa Nikolova, Denitsa Yancheva, Ventsislav Bakov, Nikolai Georgiev, Self-Assembled Molecular Complexes of 1,10-Phenanthroline and 2-Aminobenzimidazoles: Synthesis, Structure Investigations, and Cytotoxic Properties, Molecules, 2024, 29, 583. https://doi.org/10.3390/molecules29030583 (i.f. 4.6, Q2)
12. Victoria Vitkova, Krassimira Antonova, Ognyan Petkov, Angelina Stoyanova-Ivanova, Sirine Jaber, Vladislava Ivanova, Emilia Naydenova, Dancho Danalev, Interaction of KLAKLAK-NH₂ and Analogs with Biomimetic Membrane Models, Pharmaceutics, 2024, 16, 340, https://doi.org/10.3390/pharmaceutics16030340 (i.f. 5.4, Q1)
13. Dimitrova, D.; Nemska, V.; Foteva, T.; Iliev, I.; Georgieva, N.; Danalev, D., Synthesis and Biological Studies of New Temporin A Analogs Containing Unnatural Amino Acids in Position 7, Pharmaceutics, 2024, 16, 716. https://doi.org/10.3390/pharmaceutics16060716 (i.f. 5.4, Q1)
14. Sirine Jaber, Yana Evstatieva, Veronica Nemska, Dilyana Nikolova, Emilia Naydenova, Nelly Georgieva, Dancho Danalev, Antimicrobial activity of (KLAKLAK)-NH₂ analogs against pathogenic microbial strains, Current Research in Biotechnology, 2024, 8, 100236 https://doi.org/10.1016/j.crbiot.2024.100236 (i.f. 4.0, Q2)
15. Boryana Borisova, Hristina Nocheva, Ivan Iliev, Marie Laronze-Cochard, Stéphane Gérard, Stoyko Petrin, Dancho Danalev, Synthesis and analgesic activity of new analogs of FELL tetrapeptide containing D-Phe in the first position, Current Research in Biotechnology, 2024, 8, 100249, https://doi.org/10.1016/j.crbiot.2024.100249 (i.f. 4.0, Q2)
16. Konstantinos Papadakis, Kadir Bezirci, Boryana Borisova, Stanislava Vladimirova, Dancho Danalev, Teodora Handjieva-Darlenska, Radka Tafradjiiska-Hadjiolova, Hristina Nocheva, Attenuation of 1-chloro-2,4-dinitrobenzene-induced inflammation in atopic dermatitis-like skin lesions in rat by a pyrrole containing FELL-NH₂ bioconjugate: cannabinoid receptor type 1 involvement, Pharmacia, 2024, 71: 1-10. https://doi.org/10.3897/pharmacia.71.e130213 (i.f. 1.0, Q4)
17. S. Georgieva, E. Stefanov, T. Radoykova, Direct ion chromatographic method for speciation micro analysis of arsenic forms in industrial samples with “rich” matrix composition, Journal of Chromatography A, 2024, 465421, https://doi.org/10.1016/j.chroma.2024.465421 (i.f. 3.8, Q1)
18. Hristina Zlatanova-Tenisheva, Stanislava Vladimirova, Pharmacological Evaluation of Novel Hydrazide and Hydrazone Derivatives: Anti-Inflammatory and Analgesic Potential in Preclinical Models, Molecules, 2025, 30, 1472. https://doi.org/10.3390/molecules30071472 (i.f. 5.0, Q2)
19. Dilyana Dimitrova, Veronica Nemska, Ivan Iliev, Stoyko Petrin, Nelly Georgieva, Dancho Danalev, New Temporin A Analogues Modified in Positions 1 and 10 – Synthesis and Biological Studies, Pharmaceutics 2025, 17, 396. https://doi.org/10.3390/Pharmaceutics17040396 (i.f. 5.8, Q1)
20. Y. Stoyanova, N. Lazarova-Zdravkova, D. Peshev, Is Membrane Filtration Applicable for the Recovery of Biologically Active Substances from Spent Lavender? Membranes. 2025, 15, 21. https://doi.org/10.3390/membranes15010021 (i.f. 3.3, Q2)
21. Karadashka, I.; Romanova, P.; Karadjova, V. Glass Transition Temperature and Mean Bond Energy of Chalcogenide Glasses in the As2Se3-GeTe-CdTe System. Inorganics 2025, 13, 160. https://doi.org/10.3390/inorganics13050160 (i.f. 3.0, Q2)
22.  Kameliya Anichina, Galya Popova-Daskalova, Dimitar Vuchev, Maya Guncheva, Denitsa Yancheva, Nikolai Georgiev, Synthesis and In Vitro Biological Studies of Heterocyclic Benzimidazole Derivatives as Potential Therapeutics for Trichinellosis, Sci. 2025, 15, 6758. https://doi.org/10.3390/app15126758 (i.f. 2.5, Q1).
23. Kadir Bezirci, Boryana Borisova, Konstantinos Papadakis, Dancho Danalev, Hristina Nocheva, Drug Administration Before or After Exposure to Low Temperatures – Does It Matter for the Therapeutic Effect? Int. J. Mol. Sci., 2025, 26, 3883. https://doi.org/10.3390/ijms26083883 (i.f. 5.7, Q1)
24. Angelova, N., Iliev, I., Nemska, V., Dzimbova, T., Georgieva, N., Danalev, D., Naydenova, E., Design, Synthesis, and Biological Evaluation of New Analogs of Aurein 1.2 Containing Non-Proteinogenic Amino Acids, Molecules, 30(9), 2050 https://doi.org/10.3390/molecules30092050 (i.f. 5.0, Q2)
25. Neli Vilhelmova-Ilieva, Rayna Nenova, Ana Dobreva, Dimitar Peshev, Ivan Iliev, Anti-Herpes Simplex Virus Type 1 Activity of Rosa damascena Mill Essential Oil and Floral Water in Retinal Infection in Vitro, Int. J. Mol. Sci. 2025, 26, 7521. https://doi.org/10.3390/ijms26157521 (i.f. 5.7, Q1)
26. Simeon Stoyanov, Kameliya Anichina, Borislava Ivanova, Stela Georgieva, Neno Todorov, Bistra Stamboliyska and Denitsa Yancheva, Conversion of 1-alkylated 5(6)-nitro-1H-benzimidazoles into Radical Anions and Characterization of Their Bioreductive Potential, Journal of The Electrochemical Society, 172 (2025), 065501, https://doi.org/10.1149/1945-7111/ade1fc (i.f. 3.3, Q1)
27. B. Borisova, H. Nocheva, H. Zlatanova-Tenisheva, M. Laronze-Cochard, S. Gérard, D. Danalev, Synthesis and biological study of novel FELL analogs containing L- or D-Tyr instead of L-Phe in the N-terminus, Current Research in Biotechnology, 10, 2025, 100332, https://doi.org/10.1016/j.crbiot.2025.100332 (i.f. 4.5, Q2)
28. H. Zlatanova-Tenisheva, S. Vladimirova, Anti-Inflammatory and Immunomodulatory Effects of 2-(3-Acetyl-5-(4-Chlorophenyl)-2-Methyl-1H-Pyrrol-1-yl)-3-Phenylpropanoic Acid, Biomedicines, 2025, 13, 2003, https://doi.org/10.3390/biomedicines13082003 (i.f. 4.2, Q1)
29. Y. Stoyanova, N. Lazarova-Zdravkova, D. Peshev, Valorisation via nanofiltration of the antioxidant residual water from industrial hydrodistillation of rosa damascena mill. petals, J. Chem. Technol. Metall., 60(1), 2025, 3-10, https://doi.org/10.59957/jctm.v60.i1.2025.1 (SJR 0.196, Q3)
30. I. Uzunova-Raycheva, T. Nihtyanova, R. Raycheva, D. Danalev, P. Romanova, A. Belcheva-Krivorova, Infiltration level of CPP-ACFP (MI Varnish™), self-assembling peptide P11-4 (Curodont™ Repair), and newly synthesized fluorinated selfassembling peptides in artificial enamel initial carious lesions on smooth surfaces assessed by laser confocal microscopy – an in vitro study, Folia Med (Plovdiv), 2025;67(3):е151396, https://doi.org/10.3897/folmed.67.e151396 , (SJR 0.21, Q4)

31. Petar Todorov, Stela Georgieva, Diana Cheshmedzhieva, Borislav Assenov, Еlena Dzhambazova, Dimo Angelov, and Daniela Pechlivanova, Synthesis and analytical profile of new synthetic analogs of angiotensin 1‐7, the main balancing peptide of the renin–angiotensin system,  Archiv der Pharmazie 358, no. 3 (2025): e2500093; https://doi.org/10.1002/ardp.202500093

32. S. Georgieva, P. Todorov, P. Peneva, L.T.M. Hoa, Dual-Mode Chemosensing of iron ions by new Schiff Bases derived from cinnamyl 5,5′-dimethyl- and diphenylhydantoins, Results in Chemistry – under review (i.f. 4.2, Q2)
33. S. Georgieva, T. Radoykova, P. Todorov, Diana Cheshmedzhieva, Rositca Kukeva, Newly synthesized peptide-based chemosensor bearing azobenzene side chain as dual chemosensor for trace Au detection, Talanta, 2025 – under review (i.f. 3.7, Q1)
34. T. Radoykova, E. Stefanov, S. Nenkova, S. Georgieva, Antioxidant Activity of Phenolic Compounds Derived from Waste Hydrolyzed Lignocellulosic Material: A Comparative Evaluation Using Spectrophotometric and Electrochemical Methods, Cellulose, 2025 – under review (i.f. 5.6, Q1)
35. Ch. Chilev, Y. Stoyanova, N. Lazarova-Zdravkova, S. Petrin, D. Peshev, Experimental optimization of clove oil production, Journal of Essential Oil Research – under review (i.f. 2.1, Q2)
36. Vladimirova, S., Hristova, R., Iliev, I. Design, Synthesis and Biological Evaluation of Novel Methyl-Substituted Pyrrole Hydrazones as Selective Melanoma Agents, Current Research in Biotechnology, 2025 – under review (i.f. 4.0, Q2)