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

Hamideh Emtiazi; Leila  Amiri‑Zirtol; Hadi  Zare Zardini; Amir Abbas  Mohammadi Hamaneh; Soghra  Khabnadideh; Bebe Zahra Modaresi

doi:10.18502/ijpho.v16i2.21344

Hamideh Emtiazi Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Leila Amiri‑Zirtol Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Hadi Zare Zardini Hematology and Oncology Research Center, Noncommunicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Amir Abbas Mohammadi Hamaneh Department of pharmacology, School of medicine, Tehran University of Medical Sciences, Tehran, Iran
Soghra Khabnadideh Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Bebe Zahra Modaresi Chemical Engineering (Biotecnology), Faculty of Engineering, University of Tehran, Iran

DOI: https://doi.org/10.18502/ijpho.v16i2.21344

Keywords: 3-Aminopyridine, Cancer, Doxorubicin, Graphene oxide

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.