Browsing by Author "Ivanova E."

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    POLYPHENOLS OF GRAPE POMACE FROM LOCAL BULGARIAN VARIETY MAVRUD. ANTIOXIDANT AND ANTITUMOR EFFECT AGAINST BREAST CANCER
    (2022-01-01) Radoeva R.; Yankova I.; Enchev B.; Karsheva M.; Ivanova E.; Iliev I.
    Grape pomace is the main by-product of winemaking, a valuable source of polyphenols with antimicrobial, antioxidant and anti-cancer effect. Grape seeds and marcs extracts are of strategic importance for the development of new therapeutic approaches against certain cancer diseases, including breast cancer. In this study the antioxidant and antitumor potential of the polyphenolic fraction of grape pomace obtained from the vinification of the local Bulgarian grape variety Mavrud is reported. After Soxhlet extraction with 50 % water solution of ethanol, the total polyphenol content of the extracts by the Folin-Ciocalteu colorimetric method was determined. The obtained extracts were characterized by HPLC-DAD and their antioxidant activity was studied with DPPH assay. The cytotoxic effect was tested on 3T3 cell line, while MCF-7 and MDA-MB-231 breast cancer cell lines were selected to determine antitumor activity. The results showed higher total polyphenol content in the marc compared to the seed extracts and prevalence of gallic acid, catechin and epigallocatechin. A correlation between antioxidant activity and total polyphenol content was established. The studied extracts had a low cytotoxic effect, as the seed extracts showed a stronger antitumor activity compared to the extracts of marcs and potential for treatment of luminal breast cancer.
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    Rules based autotuning approach of conventional smith predictor
    (2004-01-01) Hadjiski M.; Ivanova E.
    The problem of automation of the system with large time delay take wide place in a series of contemporary researches. The main interest takes the situation when the value of system time delay considerable changes in time. In the present research is presented Smith predictor based retuning approach, as an algorithm for control of plants with large time delay, namely by such a system changes.
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    Synthesis and biological studies on (KLAKLAK)2-NH2 analog containing unnatural amino acid β-ala and conjugates with second pharmacophore
    (2021-12-01) Jaber S.; Nemska V.; Iliev I.; Ivanova E.; Foteva T.; Georgieva N.; Givechev I.; Naydenova E.; Karadjova V.; Danalev D.
    (1) Background: Peptides are good candidates for anticancer drugs due to their natural existence in the body and lack of secondary effects. (KLAKLAK)2 is an antimicrobial peptide that also shows good anticancer properties. (2) Methods: The Solid Phase Peptide Synthesis (Fmoc-strategy) was used for the synthesis of target molecules, analogs of (KLAKLAK)2-NH2. The purity of all compounds was monitored by HPLC, and their structures were proven using mass spectrometry. Cytotoxicity and antiproliferative effects were studied using 3T3 NRU and MTT tests, respectively. For determination of antimicrobial activity, the disc-diffusion method was used. Hydrolytic stability at three pH values, which mimic the physiological pH in the body, was investigated by means of the HPLC technique. (3) Results: A good selective index against MCF-7 tumor cell lines, combined with good cytotoxicity and antiproliferative properties, was revealed for conjugates NphtG-(KLAKLAK)2-NH2 and Caf-(KLAKLAK)2-NH2. The same compounds showed very good antifungal properties and complete hydrolytic stability for 72 h. The compound Caf-(KLβ-AKLβ-AK)2-NH2 containing β-Ala in its structures exhibited good antimicrobial activity against Escherichia coli K12 407 and Bacillus subtilis 3562, in combination with very good antiproliferative and cytotoxic properties, as well as hydrolytic stability. (4) Conclusions: The obtained results reveal that all synthesized conjugates could be useful for medical practice as anticancer or antimicrobial agents.
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    Synthesis, antiproliferative and antimicrobial activities of (KLAKLAK)2-NH2 analogue containing nor-Leu and its conjugates with a second pharmacophore
    (2023-01-01) Jaber S.; Nemska V.; Iliev I.; Ivanova E.; Foteva T.; Georgieva N.; Givechev I.; Tanev D.; Naydenova E.; Danalev D.
    Peptides are a promising alternative of conventional medical drugs for the treatment of different diseases because they have no or have very few side effects owing to the natural mechanisms for their elimination. There are a lot of examples of drugs on the pharmaceutical market based on modified amino acids and peptides. Herein, we report the synthesis and studies on the antimicrobial peptide (KLAKLAK)2-NH2 where Leu is replaced by the unnatural amino acid nor-Leu. In addition, a second pharmacophore with well proven anticancer properties is introduced to the peptide moiety. All structures were synthesized by conventional solid phase peptide synthesis. The antiproliferative and antimicrobial activities were studied using MTT-dye reduction assay and disk-diffusion test, respectively. Biological activity assays showed that the introduction of nor-Leu in the primary structure of the parent compound does not lead to an increase in the antiproliferative activity. However, the combination with the second pharmacophore 1,8-naphtalimide in a hybrid structure 1,8-NphtG-(KNleAKNleAK)2-NH2 leads to a significant increase in the antiproliferative properties. The antimicrobial tests showed that all tested compounds exhibit antimicrobial activity. The peptide and the second pharmacophore had a synergistic effect. In combination with complete hydrolytic stability for 72 h in model systems, the compound 1,8-NphtG-(KNleAKNleAK)2-NH2 is the best candidate for a medical drug in the treatment of mammary gland type A adenocarcinoma (MCF-7) in combination with antimicrobial properties.
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    Synthesis, Antiproliferative Effect and In Silico LogP Prediction of BIM-23052 Analogs Containing Tyr Instead of Phe
    (2023-04-01) Danalev D.; Iliev I.; Dobrev S.; Angelova S.; Petrin S.; Dzimbova T.; Ivanova E.; Borisova D.; Naydenova E.
    (1) Background: Hydrophobicity (or lipophilicity) is a limiting factor in the ability of molecules to pass through cell membranes and to perform their function. The ability to efficiently access cytosol is especially important when a synthetic compound has the potential to become a drug substance. D-Phe-Phe-Phe-D-Trp-Lys-Thr-Phe-Thr-NH2 (BIM-23052) is a linear analog of somatostatin with established in vitro GH-inhibitory activity in nanomolar (nm) concentrations and high affinity to different somatostatin receptors. (2) Methods: Series of analogs of BIM-23052 were synthesized where Phe residue(s) in the BIM-23052 molecule were replaced with Tyr using standard SPPS, Fmoc/t-Bu strategy. Analyses of target compounds were performed using HPLC/MS technique. Toxicity and antiproliferative activity were studied using in vitro NRU and MTT assays. The values of logP (partition coefficient in octanol/water) for BIM-23052 and its analogs were calculated. (3) Results: The obtained data show the best antiproliferative effect against studied cancer cells for compound D-Phe-Phe-Phe-D-Trp-Lys-Thr-Tyr7-Thr-NH2 (DD8), the most lipophilic compound according to the predicted logP values. (4) Conclusions: Multiple analyses of the obtained data reveal that compound D-Phe-Phe-Phe-D-Trp-Lys-Thr-Tyr7-Thr-NH2 (DD8) where one Phe is replaced by Tyr has the best combination of cytotoxicity, antiproliferative effect and hydrolytic stability.