Synthesis of Dhydropyrano[3,2-C]Chromenes in the Presence of Effective Acid–Base Nano Catalyst (3-Aminopyridin/Go) and Evaluation of Their Toxicity Against Cancer Cells Publisher



Emtiazi H ; Amirizirtol L ; Zardini HZ ; Hamaneh AAM ; Khabnadideh S ; Modaresi BZ
Source: Iranian Journal of Pediatric Hematology and Oncology Published:2026

Abstract

Background: Dihydropyrano[3,2-c]chromenes are oxygen-containing heterocycles with reported anticancer potential, yet green and efficient synthetic methods remain limited. Conventional catalysts often involve harsh conditions or low reusability. This study aimed to develop a sustainable, high-yield synthesis of chromenes via a novel acid–based nanocatalyst (GO/3-aminopyridine), and to evaluate the cytotoxicity of selected derivatives against cancer and normal cells. Materials and Methods: In this in vitro experimental study, we performed a one-pot, three-component reaction of 4-hydroxycoumarin, malononitrile or ethyl cyanoacetate, and aromatic aldehydes in the presence of 3-aminopyridine-functionalized graphene oxide (GO/3-APy) under mild conditions (EtOH/H2O 50 °C). The structure of the catalyst and products were confirmed via FT‑IR, NMR, XRD, FE-SEM, and EDS. MTT assay was used to determine IC50 values for selected compounds against Ovcar3, T47D, CA46, and HFF cell lines. Doxorubicin served as a positive control. Statistical analyses were done by SPSS (Version 22.0). ANOVA test was performed to identify significant differences in IC50 values across all tested compounds and doxorubicin. P-value < 0.05 was considered significant. Results: Compound 4b exhibited potent cytotoxicity against Ovcar3 (IC50 = 14.67 ± 1.15 µg/mL), T47D (26.85 ± 2.10 µg/mL), and CA46 (27.17 ± 1.55 µg/mL) cells, significantly surpassing doxorubicin against CA46 (46.07 ± 2.80 µg/mL; p < 0.05). Compound 4d showed comparable activity (IC50 = 17.99 ± 1.42, 29.50 ± 1.85, and 56.62 ± 2.90 µg/mL, respectively) with high selectivity for cancer cells over normal HFF (IC50 = 239.25 ± 5.50 µg/mL; selectivity index ~13). Compounds 4e, 4g, and 4h demonstrated moderate cytotoxicity (IC50 = 33.50–141.52 µg/mL), while doxorubicin displayed non-selective toxicity toward normal cells (IC50 = 50.45 ± 2.90 µg/mL vs. 239.25 µg/mL for 4d). Conclusion: The results of our research showed that dihydropyrano[3,2-c]chromene derivatives showed anticancer effects that depended on the type of substitution present on the ring in their structure. © (2026), (Shahid Sadoughi University of Medical Sciences). All rights reserved.