Browsing by Author "Dzimbova T."
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Item COMPUTER MODELLING OF ALL TYPES OF SOMATOSTATIN RECEPTORS(2020-01-01) Dzimbova T.; Wesselinova D.; Naydenova E.; Milanov P.The somatostatin receptors (SSTRs) are a very important class of receptors that attract the attention of a great number of scientists. The development of effective and selective ligands of each somatostatin receptor type is a time consuming process, which involves the knowledge and the skills of different researchers: chemists, biologists, medics, pharmacologists, etc. A large number of compounds is synthesized, characterized and biologically tested, but just some of them have the desired efficacy and selectivity to a respective somatostatin receptor type. The aims of the present study are: (1) to choose templates, among the recently published crystallographic structures, for homology modelling of all five types of SSTRs; (2) to evaluate the models by different computational tools (Procheck, MolProbity, docking). The structures of SSTRs are modelled using the Chimera software and their characteristics are evaluated on the ground of different methods. The best models are used for docking with recently synthesized and biologically tested somatostatin analogues selective to certain SSTR. The data, especially from docking, shows that the newly generated model of SSTRs could be further used for in silico experiments providing a faster and a better design of selective and effective ligands of SSTRsItem 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.