LABORATORY CYTOTOXICITY AND SIGNAL TRANSDUCTION – The Stephan Angeloff Institute of Microbiology

Characterization of the toxicological profile of compounds, extracts, etc. products with antineoplastic and antibacterial activities by phenotypic and molecular biological methods.
Elucidation of the relationship between bacterial infections and carcinogenesis in malignant diseases localized in tissues and organs in contact with the external environment (neoplasms of the skin, oral cavity, gastrointestinal tract, etc.) – in collaboration with the Laboratory “Bacterial Virulence, Resistance and New Antimicrobial Agents”.
Investigation of mechanisms of bacterial virulence (signal transduction, programmed cell death, etc.) in interactions between bacterial pathogens and host cells – in collaboration with the Laboratory “Bacterial Virulence, Resistance and New Antimicrobial Agents”.
Determination of combined antineoplastic and antimicrobial activities of natural products of plant or microbial origin, biologically active compounds derived thereof; newly synthesized chemical compounds, as well as modulated ones with nano-, metal- and other structures. The antimicrobial activity is studied in collaboration with the Laboratory “Bacterial Virulence, Resistance and New Antimicrobial Agents”.

SELECTED PUBLICATIONS:

Diukendjieva, A*, Zaharieva, MM*, Mori, M, Alov, P, Tsakovska, I, Pencheva, T, Najdenski, H, Kren, V, Felici, C, Bufalieri, F, Di Marcotullio, L, Botta, B, Botta M, Pajeva I. Dual SMO/BRAF Inhibition by Flavonolignans from Silybum marianum. Antioxidants (Basel), 9, 5, MBPI, 2020. ISSN:2076-3921 (Print), 2076-3921 (Electronic), 2076-3921 (Linking), DOI:antiox9050384 [pii], antioxidants-09-00384 [pii], 10.3390/antiox9050384 [doi], 384. JCR-IF (Web of Science): 6.313, Q1 (Scopus), *Shared first place

https://www.mdpi.com/2076-3921/9/5/384

Schuelter, AR, Kroumov, AD, Hinterholz, CL, Fiorini, A, Trigueros, DEG, Vendruscolo, EG, Zaharieva, MM, Modenes, AN. Isolation and identification of new microalgae strains with antibacterial activity on food-borne pathogens. Engineering approach to optimize synthesis of desired metabolites. Biochemical Engineering Journal, 144, Elsevier, 2019, ISSN:1369-703X, DOI:10.1016/j.bej.2019.01.007, 28-39. JCR-IF (Web of Science): 3.475, Q1 (Scopus)

https://www.sciencedirect.com/science/article/pii/S1369703X19300075?via%3Dihub

Gevrenova, R, Zaharieva, MM, Kroumov, AD, Voutquenne-Nazabadioko, L, Zheleva-Dimitrova, D, Balabanova, V, Najdenski, H, Konstantinov, S. Gypsophila saponins enhance the cytotoxicity of etoposide in HD-MY-Z lymphoma cells. Food and Chemical Toxicology, 133, Elsevier, 2019, ISSN:0278-6915, DOI:10.1016/j.fct.2019.110777, 110777. JCR-IF (Web of Science): 4.679, Q1 (Scopus)

https://www.sciencedirect.com/science/article/pii/S0278691519305678?via%3Dihu

Scheufele, FB, Hinterholz, CL, Zaharieva, MM, Najdenski, H, Módenes, AN, Trigueros, DEG, Borba, C, Espinoza-Quiñones, FR, Kroumov, AD. Complex mathematical analysis of photobioreactor system. Engineering in Life Sciences, John Wiley & Sons Ltd., 2019, ISSN:1618-2863, DOI:10.1002/elsc.201800044, 1-14. JCR-IF (Web of Science): 1.934, Q2 (Scopus)

https://onlinelibrary.wiley.com/doi/10.1002/elsc.201800044

Nedialkov, PT, Ilieva Y, Zheleva-Dimitrova D, Kokanova-Nedialkova Z, Momekov G. Three new prenyloxy chromanones from aerial parts of Hypericum aucheri. Fitoterapia, 139, 2019. DOI:https://doi.org/10.1016/j.fitote.2019.104421. ISSN:0367-326X, 104421 JCR-IF (Web of Science): 2.527, Q2 (Scopus)

https://www.sciencedirect.com/science/article/abs/pii/S0367326X19319549

Zaharieva, MM, Kroumov, AD, Dimitrova, L, Tsvetkova, I, Trochopoulos, A, Konstantinov, SM, Berger, MR, Momchilova, M, Yoncheva, K, Najdenski, HM. Micellar curcumin improves the antibacterial activity of the alkylphosphocholines erufosine and miltefosine against pathogenic Staphyloccocus aureus strains. Biotechnology & Biotechnological Equipment, 33, 1, Fransis & Taylor, 2019, ISSN:1310-2818, DOI:10.1080/13102818.2018.1533792, 38-53. JCR-IF (Web of Science): 1.186, Q3 (Scopus)

https://doi.org/10.1080/13102818.2018.1533792

Kaleağasıoğlu, F*, Zaharieva, MM*, Konstantinov, S, Berger, MR. Alkylphospholipids are Signal Transduction Modulators with Potential for Anticancer Therapy. Anti-Cancer Agents in Medicinal Chemistry, 19, 1, Bentham Science Publishers, 2019, ISSN:1389-5575, DOI:10.2174/1871520618666181012093056, 66-91. JCR-IF (Web of Science): 2.049, Q3 (Scopus)

https://www.eurekaselect.com/node/166176/article/alkylphospholipids-are-signal-transduction-modulators-with-potential-for-anticancer-therapy

*Shared first place

Zaharieva, M. M., Trochopoulos, A., Dimitrova, L., Berger, M. R., Najdenski, H., Konstantinov, S., Kroumov, A. D. New Insights in Routine Procedure for Mathematical Evaluation of in vitro Cytotoxicity Data from Cancer Cell Lines. 22, 2, International Journal Bioautomation, 2018, DOI:10.7546/ijba.2018.22.2.87-106, 87-106. SJR (Scopus): 0.231, Q3 (Scopus)

https://www.scopus.com/record/display.uri?eid=2-s2.0-85048438585&origin=resultslist&sort=plf-f&src=s&st1=New+Insights+in+Routine+Procedure+for+Mathematical+Evaluation+of+in+vitro+Cytotoxicity+Data+from+Cancer+Cell+Lines&st2=&sid=0f506fd8b85924ee22a18%22origin=resultslist

Zheleva-Dimitrova, D., Gevrenova, R., Zaharieva, M. M., Najdenski, H., Ruseva, S., Lozanov, Valentin, Balabanova, V., Yagi, S., Momekov, G., Mitev, V.. HPLC-UV and LC–MS Analyses of Acylquinic Acids in Geigeria alata (DC) Oliv. & Hiern. and their Contribution to Antioxidant and Antimicrobial Capacity. Phytochemical analysis, John Wiley & Sons Ltd, 2017, ISSN:1099-1565, DOI:10.1002/pca.2658, n/a-n/a-n/a-n/a. JCR-IF (Web of Science): 2.337, Q1 (Scopus)

http://onlinelibrary.wiley.com/doi/10.1002/pca.2658/pdf

Zaharieva, M.M., Kirilov, M., Chai, M., Berger, S.M., Konstantinov, S., Berger, M.R.. Reduced expression of the retinoblastoma protein shows that the related signaling pathway is essential for mediating the antineoplastic activity of erufosine. PLoS ONE, 9, 7, PLOS, 2014, ISSN:1932-6203, DOI:http://dx.doi.org/10.1371/journal.pone.0100950, e100950. JCR-IF (Web of Science): 3.234, Q1 (Web of Science)

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0100950

Voutquenne-Nazabadioko, L., Gevrenova, R., Borie, N., Harakat, D., Sayagh, C., Weng, A., Thakur, M., Zaharieva, M., Henry, M.. Triterpenoid saponins from the roots of Gypsophila trichotoma Wender. Phytochemistry, 90, ELSEVIER, 2013, ISSN:0031-9422, DOI:10.1016/j.phytochem.2013.03.001, 114-127. JCR-IF (Web of Science): 3.05, Q1 (Scopus)

http://www.sciencedirect.com/science/article/pii/S0031942213000769

Kapoor, V., Zaharieva, M.M., Das, S.N., Berger, M.R. Erufosine simultaneously induces apoptosis and autophagy by modulating the Akt-mTOR signaling pathway in oral squamous cell carcinoma. Cancer Letters, 319, 1, ELSEVIER, 2012, ISSN:03043835, DOI:10.1016/j.canlet.2011.12.032, 39-48. JCR-IF (Web of Science): 4.258, Q1 (Web of Science)

http://www.sciencedirect.com/science/article/pii/S0304383511007919

ACHIEVEMENTS:

The foundations of the Laboratory “Cytotoxicity and Signal Transduction”, funded by a grant for Assoc. Prof. Maya M. Zaharieva donated by the Alexander von Humboldt Foundation under the Program “Equipment Subsidy”, have been laid. The laboratory was officially opened on April 22, 2015 by Mr. Jörg Schenk, Head of the Science Department at the Embassy of the Federal Republic of Germany in Sofia. The duration of the Laboratory development was 5 years, as set out in the grant program. During that period a number of projects related to the above mentioned directions were started and successfully finished. The laboratory takes part in several on-going projects: two national scientific programs, five grants funded from the National Bulgarian Scientific Fund, grants in the frame of collaborations with other scientific institutions. A number of graduate and PhD students conducted their practices and training here.
The antibacterial effect and biofilm-inhibitory activity of the new allylphosphocholine erufosine on methicillin-sensitive and resistant strains of the bacterial pathogen Staphylococcus aureus, which is involved in the carcinogenesis of cutaneous T-cell lymphoma (CTCL), were studied for the first time. Combinations between erufosine and curcumin loaded in nano-delivery system with sustained release were investigated for synergistic interactions on cell lines derived from CTCL. It has been proven for the first time that erufosine and the synergistic combinations with curcumin inhibit the expression of the transcription factor TWIST1, which is a prognostic marker for metastasis in patients with CTCL.
The antineoplastic activity and mechanism of action of combinations between Glucuronide Oleanane-type Triterpenoid Carboxylic Acid 3,28-Bidesmosides derived from Gypsophila trichotoma Wender roots and the cytostatics etoposide, as well as plant extracts and biologically active compounds isolated from Geum urbanum were invstigated for the first time on malignant cell lines of lymphoma and epithelial origin. The toxicological effects of ethyl acetate extract from aerial parts of Geum urbanum L. were evaluated in vitro on a panel of normal transformed cell lines and in vivo on liver, intestinal epithelium and kidney in H albino mice.
The antibacterial effects of Geigeria alata (DC) Oliv. & Hiern., Solanum schimperianum Hochst and Graptopetalum paraguayense E. Walther plant extracts was studied on Gram-positive and Gram-negative pathogenic bacterial species. The antibacterial activity of the plant Geum urbanum L was studied partially.
The cytotoxic effect of a number of medical products was evaluated and described under contracts with companies, which is of direct importance for their production and release on the pharmaceutical market.