New Pyrrole Derivatives as Promising Biological Agents: Design, Synthesis, Characterization, In Silico, and Cytotoxicity Evaluation
Autor: | Beatrice-Cristina Ivan, Stefania-Felicia Barbuceanu, Camelia Mia Hotnog, Adriana Iuliana Anghel, Robert Viorel Ancuceanu, Mirela Antonela Mihaila, Lorelei Irina Brasoveanu, Sergiu Shova, Constantin Draghici, Octavian Tudorel Olaru, George Mihai Nitulescu, Mihaela Dinu, Florea Dumitrascu |
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Rok vydání: | 2022 |
Předmět: |
Molecular Structure
Organic Chemistry Endothelial Cells Antineoplastic Agents General Medicine Catalysis Computer Science Applications Inorganic Chemistry Biological Factors Structure-Activity Relationship pyrroles dipolarophile alkynes [3 + 2] cycloaddition X-ray diffraction cytotoxicity antitumor activity Cell Line Tumor Animals Humans Female Pyrroles Drug Screening Assays Antitumor Physical and Theoretical Chemistry Molecular Biology Spectroscopy Cell Proliferation |
Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 16; Pages: 8854 |
ISSN: | 1422-0067 |
DOI: | 10.3390/ijms23168854 |
Popis: | The current study describes the synthesis, physicochemical characterization and cytotoxicity evaluation of a new series of pyrrole derivatives in order to identify new bioactive molecules. The new pyrroles were obtained by reaction of benzimidazolium bromide derivatives with asymmetrical acetylenes in 1,2-epoxybutane under reflux through the Huisgen [3 + 2] cycloaddition of several ylide intermediates to the corresponding dipolarophiles. The intermediates salts were obtained from corresponding benzimidazole with bromoacetonitrile. The structures of the newly synthesized compounds were confirmed by elemental analysis, spectral techniques (i.e., IR, 1H-NMR and 13C-NMR) and single-crystal X-ray analysis. The cytotoxicity of the synthesized compounds was evaluated on plant cells (i.e., Triticum aestivum L.) and animal cells using aquatic crustaceans (i.e., Artemia franciscana Kellogg and Daphnia magna Straus). The potential antitumor activity of several of the pyrrole derivatives was studied by performing in vitro cytotoxicity assays on human adenocarcinoma-derived cell lines (i.e., LoVo (colon), MCF-7 (breast), and SK-OV-3 (ovary)) and normal human umbilical vein endothelial cells (HUVECs). The obtained results of the cytotoxicity assessment indicated that the tested compounds had nontoxic activity on Triticum aestivum L., while on Artemia franciscana Kellogg nauplii, only compounds 2c and 4c had moderate toxicity. On Daphnia magna, 4b and 4c showed high toxicity; 2a, 2b, and 2c moderate to high toxicity; only 4a and 4d were nontoxic. The compound-mediated cytotoxicity assays showed that several pyrrole compounds demonstrated dose- and time-dependent cytotoxic activity against all tested tumor cell lines, the highest antitumor properties being achieved by 4a and its homologue 4d, especially against LoVo colon cells. |
Databáze: | OpenAIRE |
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