One-pot three-component synthesis of novel pyrano[3,2-e]pyrazolo[1,5-a]pyrimidines and investigation of their biological activities

• Published in: Journal of molecular structure 2023-07, Vol.1284, p.135446, Article 135446
• Main Authors: Vahedi, Mohammad Mehdi, Asghari, Sakineh, Tajbakhsh, Mahmood, Mohseni, Mojtaba, Khalilpour, Asieh
• Format: Article
• Language: English
• Subjects: Antibacterial; Antioxidant; Cytotoxicity; Pyrano[3,2-e]pyrazolo[1,5-a]pyrimidine; Three-component reaction
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.135446

•Sixteen novel polyheterocyclic compounds were created in high yields (>80%) via three-component reaction.•The synthesized compounds showed good to high cytotoxicity against MCF-7 cancer cell line.•The products demonstrated high to excellent anti-oxidant activities.•These compounds exhibited moderate antibacterial properties only against Gram-positive bacteria. In this study, pyrano[3,2-e]pyrazaolo[1,5-a]pyrimidine derivatives were produced in high yields (80–89%), at room temperature, by three-component reactions involving alkyl isocyanides, dialkyl acetylenedicarboxylates, and 7‑hydroxy pyrazolo[1,5-a]pyrimidines. Using FT-IR, 1H and 13C NMR, and mass spectral data, the structure of the synthesized compounds was identified. The created molecules were tested against cancer, bacteria, and free radicals to evaluate how effective they could be. It was determined whether or not the tested substances had any cytotoxic effects on the MCF-7 (breast cancer) and the MCF-10 (breast epithelial) cell lines. Compound 4l, in comparison to other compounds, has shown the most potent anti-cancer activity (IC50=19.70±0.89 µM), which is roughly as excellent as the standard medicine etoposide (IC50= 18.71±1.09 µM). Also, the antioxidant properties of the products were investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The results demonstrated that compound 4 h had the highest free radical scavenging effect (IC50= 12.12±0.40 µM), which was very close to the value for ascorbic acid (IC50= 11.85±0.30 µM), as the antioxidant standard. The Kirby-Bauer disk diffusion technique was applied to examine the bactericidal impact of the synthesized compounds. According to the findings, virtually all the compounds had a modest level of action against Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus). [Display omitted]