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Registration Number

0225U003533, (0125U002229) , R & D reports

Title

Molecular design, synthesis and biological activity of small heterocyclic molecules based on azolidines with a polypharmacological profile

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Молекулярний дизайн, синтез і біологічна активність малих гетероциклічних молекул на основі азолідинів із поліфармакологічним профілем

Head

Kryshchyshyn-Dylevych Anna P., Доктор фармацевтичних наук

Registration Date

09-07-2025

Organization

Kryshchyshyn-Dylevych Anna P.

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The directed design and synthesis of small heterocyclic molecules – azolidine derivatives as polypharmacological "drug-like molecules" based on the obtained experimental data of in vitro and in silico studies, prediction and evaluation of their pharmacological activity using computer chemistry methods, in silico study of molecular mechanisms of antitumor, antiparasitic and antibacterial activity

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 In the presented study a number of new heterocyclic compounds were designed and synthesized: 5-ylidene-3-(1-arylpyrrolidine-2,5-dione)-rhodanines, 2-cyanoacetamides with thiazolidine fragments, and N-substituted thiopyranothiazoles. Their antimicrobial, antifungal, anticancer, antitrypanosomal, and antiviral activities were studied. According to the results of microbiological screening, compounds with high activity against Staphylococcus aureus and Candida albicans were identified. Pharmacophore screening was performed using protein targets of topoisomerase IV (PDB ID: 4HY1) and sterol 14α-demethylase (PDB ID: 6UEZ) that confirmed potent biological activity of the synthesized molecules. Molecular docking revealed high level of binding of a number of derivatives to the indicated enzymes. Additionally, machine learning methods, namely the K-means and agglomerative hierarchical clustering were applied to classify thiazolidine and pyrazoline derivatives that allowed identifying a group of compounds with dual antitrypanosomal and antiproliferative activity. Pharmacophore modeling based on the BCL-2–venetoclax complex proved potential inhibitors’ high pharmacophore-fit scores to pharmacophore models. Studies of the antiviral activity of a number of thiopyranothiazole derivatives allowed us to identify molecules with high cytopathic effects against influenza A (H1N1), influenza B and SARS-CoV viruses. The obtained results confirm the feasibility of further molecular optimization of these heterocycles as promising antiviral agents.

Product Description

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Kryshchyshyn-Dylevych Anna P.

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2025-07-09