Novel Bis- and Mono-Pyrrolo[2,3-d]pyrimidine and Purine Derivatives: Synthesis, Computational Analysis and Antiproliferative Evaluation
| Autor: | Mirela Sedić, Krešimir Pavelić, Sandra Kraljević Pavelić, Andrea Bistrovic Popov, Petra Grbčić, Robert Vianelo, Silvana Raić-Malić |
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| Přispěvatelé: | Vianelo, Robert [0000-0003-1779-4524], Grbčić, Petra [0000-0002-5711-6237], Sedić, Mirela [0000-0003-4679-1541], Pavelić, Sandra Kraljević [0000-0003-0491-673X], Pavelić, Krešimir [0000-0001-7706-6858], Raić-Malić, Silvana [0000-0001-5021-8970], Apollo - University of Cambridge Repository |
| Jazyk: | chorvatština |
| Rok vydání: | 2021 |
| Předmět: |
Purine
Pharmaceutical Science DFT calculations 01 natural sciences 7. Clean energy Analytical Chemistry HeLa chemistry.chemical_compound QD241-441 0302 clinical medicine pyrrolo[2 3‐d]pyrimidines purine ultrasound antiproliferative activity pancreatic adenocarcinoma apoptosis Drug Discovery Density Functional Theory Cycloaddition Reaction biology Chemistry Cycloaddition 3. Good health Chemistry (miscellaneous) 030220 oncology & carcinogenesis Molecular Medicine Adenocarcinoma Pyrimidine Cell Survival Stereochemistry Triazole Antineoplastic Agents pyrrolo[2 3-d]pyrimidines Article 03 medical and health sciences Cell Line Tumor Pancreatic cancer medicine Humans Pyrroles Physical and Theoretical Chemistry Cell Proliferation 010405 organic chemistry Organic Chemistry medicine.disease biology.organism_classification 0104 chemical sciences Pyrimidines A549 Cells Drug Screening Assays Antitumor Linker HeLa Cells |
| Zdroj: | Molecules Molecules, Vol 26, Iss 3334, p 3334 (2021) Volume 26 Issue 11 |
| Popis: | Novel symmetrical bis-pyrrolo[2,3-d]pyrimidines and bis-purines and their monomers were synthesized and evaluated for their antiproliferative activity in human lung adenocarcinoma (A549), cervical carcinoma (HeLa), ductal pancreatic adenocarcinoma (CFPAC-1) and metastatic colorectal adenocarcinoma (SW620) cells. The use of ultrasound irradiation as alternative energy input in Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) shortened the reaction time, increased the reaction efficiency and led to the formation of exclusively symmetric bis-heterocycles. DFT calculations showed that triazole formation is exceedingly exergonic and confirmed that the presence of Cu(I) ions is required to overcome high kinetic requirements and allow the reaction to proceed. The influence of various linkers and 6-substituted purine and regioisomeric 7-deazapurine on their cytostatic activity was revealed. Among all the evaluated compounds, the 4-chloropyrrolo[2,3-d]pyrimidine monomer 5f with 4,4′-bis(oxymethylene)biphenyl had the most pronounced, although not selective, growth-inhibitory effect on pancreatic adenocarcinoma (CFPAC-1) cells (IC50 = 0.79 µM). Annexin V assay results revealed that its strong growth inhibitory activity against CFPAC-1 cells could be associated with induction of apoptosis and primary necrosis. Further structural optimization of bis-chloropyrrolo[2,3-d]pyrimidine with aromatic linker is required to develop novel efficient and non-toxic agent against pancreatic cancer. |
| Databáze: | OpenAIRE |
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