Green synthesis, one-pot reaction, biological evaluation, and molecular docking studies of new pyrazolo[3,4-d]tetrazolo[1,5-a]pyrimidine derivatives
摘要
The work represents a synthesized strategy for a range of novel pyrazolotriazole pyrimidine derivatives using a one-pot, three-component reaction involving 5-aminotetrazole, aromatic aldehydes, and 3-methyl-5-pyrazolone. The structure of the synthesized compounds was confirmed by IR, NMR, and mass spectroscopies. Their anticancer properties were assessed against various cell lines using the in vitro MTT method. Among the tested compounds, 4c demonstrated the most potent antitumor activity. Compound 4c showed an IC50 value of 6.8 µM against MDA-MB-231 cells, while 4c exhibited an IC50 value of 4.9 µM against HCT-116 cells. These results were compared to the performance of Vinblastine used as a reference compound. Antimicrobial assays were conducted on all the newly prepared compounds against selected (bacterial & fungal) strains. The results revealed that compounds (4c, 4a, 4d, and 4f) demonstrated the most potent antibacterial and antifungal properties among the studied series. Moreover, antioxidant activity was studied using the DPPH assay, and the hydroxyl-substituted derivative 4f showed the strongest free radical scavenging ability (IC50 = 26.9 ± 1.5 µg/mL), which is attributed to the presence of hydroxyl groups that are known to stabilize radicals through hydrogen donation. Furthermore, the correlation between the compounds’ structures as well as their biological activities was investigated for a better understanding of their mechanisms of action. This work studied a molecular docking evaluation of newly synthesized compounds (4c and 4f), aiming to explore their biological activities, including antibacterial, antifungal, antioxidant, and anticancer influences.