Browsing by Author "Dobrev S."

Now showing 1 - 4 of 4
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    Density Functional Theory Prediction of Laser Dyes–Cucurbit[7]uril Binding Affinities
    (2024-09-01) Petkova V.; Dobrev S.; Kircheva N.; Nazarova D.; Nedelchev L.; Nikolova V.; Dudev T.; Angelova S.
    Among a variety of diverse host molecules distinguished by specific characteristics, the cucurbit[n]uril (CB) family stands out, being widely known for the attractive properties of its representatives along with their increasingly expanding area of applications. The presented herewith density functional theory (DFT)-based study is inspired by some recent studies exploring CBs as a key component in multifunctional hydrogels with applications in materials science, thus considering CB-assisted supramolecular polymeric hydrogels (CB-SPHs), a new class of 3D cross-linked polymer materials. The research systematically investigates the inclusion process between the most applied representative of the cavitand family CB[7] and a series of laser dye molecules as guests, as well as the possible encapsulation of a model side chain from the photoanisotropic polymer PAZO and its sodium-containing salt. The obtained results shed light on the most significant factors that play a key role in the recognition process, such as binding mode, charge, and dielectric constant of the solvent. The observed findings provide valuable insights at a molecular level for the design of dye–CB[7] systems in various environments, with potential applications in intriguing and prosperous fields like photonics and material science.
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    ISOLATION AND CHARACTERIZATION OF PEPTIDES FROM MILK AS NATURAL INHIBITORS OF ACE I AND FOOD ADDITIVES
    (2024-01-01) Yakimova B.; Alexova R.; Dobreva L.; Rainova Y.; Dobrev S.; Danova S.; Angelova S.; Stoineva I.
    Inhibition of Angiotensin-converting enzyme I (ACE I) is a modern therapeutic approach to treatment of hypertension. In recent years, research into natural ACE peptide inhibitors without side effects has become important. The aim of this study is to isolate and characterize novel bioactive peptides from skim and/or whole cow’s milk fermented with selected lactobacillus strains. Several homo/heterofermentative strains of the Lactobacillus species of dairy origin have been pre-selected and different milk fermented samples have been studied. A protocol for analyses was designed and the milk proteins were separated by centrifugation at 4°C at 10000 × g, with molecular mass cut off (MWCO) membranes of 3 and 10 kDa. The samples with molecular mass below 3 kDa were further separated by ultrafiltration by dialysis cell (cut off membrane 1 kDa) by continuous stirring at room temperature. The milk fractions under 1 kDa molecular mass were characterized by UPLC-MS. The ACE-inhibitory activity was determined using the FAPGG (N-[3-(2-Furyl) acryloyl]-L-phenylalanyl-glycyl-glycine) degradation method. All tested samples (1 kDa) exhibit ACE I inhibitory activity with IC50 in a range of 6 - 37 mg mL-1. In silico logP prediction of selected peptides was used to assess whether lipophilicity of the compounds falls within the so-called “therapeutically relevant pharmacokinetic space”.
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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.
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    Synthesis, In Silico Logp Study, and In Vitro Analgesic Activity of Analogs of Tetrapeptide FELL
    (2023-08-01) Borisova B.; Nocheva H.; Gérard S.; Laronze-Cochard M.; Dobrev S.; Angelova S.; Petrin S.; Danalev D.
    Background: The inflammatory process represents a specific response of the organism’s immune system. More often, it is related to the rising pain in the affected area. Independently of its origin, pain represents a complex and multidimensional acute or chronic subjective unpleasant perception. Currently, medical doctors prescribe various analgesics for pain treatment, but unfortunately, many of them have adverse effects or are not strong enough to suppress the pain. Thus, the search for new pain-relieving medical drugs continues. Methods: New tetrapeptide analogs of FELL with a generaanalgesic-Glu-X3-X4-Z, where X = Nle, Ile, or Val and Z = NH2 or COOH, containing different hydrophobic amino acids at positions 3 and 4, were synthesized by means of standard solid-phase peptide synthesis using the Fmoc/OtBu strategy in order to study the influence of structure and hydrophobicity on the analgesic activity. The purity of all compounds was monitored by HPLC, and their structures were proven by ESI-MS. Logp values (partition coefficient in octanol/water) for FELL analogs were calculated. Analgesic activity was examined by the Paw-pressure test (Randall-Selitto test). Results: The obtained results reveal that Leu is the best choice as a hydrophobic amino acid in the FELL structure. Conclusions: The best analgesic activity is found in the parent compound FELL and its C-terminal amide analog.