Synthesis, Antiproliferative Effect and In Silico LogP Prediction of BIM-23052 Analogs Containing Tyr Instead of Phe

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creativework.keywordsantiproliferative effect, BIM-23052 analogs, cytotoxicity, lipophilicity, somatostatin
creativework.publisherMultidisciplinary Digital Publishing Institute (MDPI)en
dc.contributor.authorDanalev D.
dc.contributor.authorIliev I.
dc.contributor.authorDobrev S.
dc.contributor.authorAngelova S.
dc.contributor.authorPetrin S.
dc.contributor.authorDzimbova T.
dc.contributor.authorIvanova E.
dc.contributor.authorBorisova D.
dc.contributor.authorNaydenova E.
dc.date.accessioned2024-07-10T14:27:05Z
dc.date.accessioned2024-07-10T14:50:39Z
dc.date.available2024-07-10T14:27:05Z
dc.date.available2024-07-10T14:50:39Z
dc.date.issued2023-04-01
dc.description.abstract(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.
dc.identifier.doi10.3390/pharmaceutics15041123
dc.identifier.issn1999-4923
dc.identifier.scopusSCOPUS_ID:85154613846en
dc.identifier.urihttps://rlib.uctm.edu/handle/123456789/827
dc.language.isoen
dc.source.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85154613846&origin=inward
dc.titleSynthesis, Antiproliferative Effect and In Silico LogP Prediction of BIM-23052 Analogs Containing Tyr Instead of Phe
dc.typeArticle
oaire.citation.issue4
oaire.citation.volume15
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