Background:Organoselenium (OSe) agents and Schiff bases have demonstrated
immense potential in the pharmaceutical field due to their broad spectrum of medicinal activities.Methods:We herein report the antitumor activities of bis diselenide-based Schiff bases
(3a-3c) derived from bis(4-aminophenyl)diselenide 2 and organoselenide-based Schiff bases
(5a-c) derived from p-(methylselanyl)phenyl amine (4). The antitumor activity was estimated
against fifteen cancer cell lines. Also, the growth inhibition percentage (GI%) of the
Schiff bases tethered OSe compounds was evaluated against two normal cell lines, namely,
human skin fibroblasts (HSF) and olfactory ensheathing cell line (OEC), to estimate the potential
safety and selectivity. Furthermore, the cytotoxic inhibitory concentration 50 (IC50)
was assessed against the cancer cell lines with the most outstanding GI% using the SRB assay.Results:Compounds 3a, 3b, 3c, and 5a showed the lowest IC50 values compared to those of
doxorubicin (DOX) against HCT116, HEPG2, A549, MDA-MB-468, and FaDu cancer cell
lines, respectively, especially against the HCT116 subtype, assuring their potential anticancer
activity. On the other side, the apoptotic potentials of the most active compounds (3a, 3b, 3c,
and 5a) were also evaluated for apoptosis-related genes (P53, BAX, caspases 3, 6, 8, and 9,
MMP2, MMP9, and BCL-2). Interestingly, compounds 3a, 3b, 3c, and 5a upregulated P53,
BAX, and caspases 3, 6, 8, and 9 by (2.66, 2.26, 2.44, and 2.57)-, (1.62, 1.52, 1.37, and
1.47)-, (1.87, 1.75, 2.02, and 1.75)-, (1.96, 1.74, 2.06, and 2.30)-, (4.25, 3.78, 3.53, and
3.96)-, and (2.04, 1.72, 1.90, and 1.63)-fold change, respectively. Furthermore, MMP2, MMP9,
and BCL-2 were downregulated by (0.39, 0.51, 0.33, and 0.28)-, (0.29, 0.32, 0.37, and
0.41)-, and (0.42, 0.35, 0.29, and 0.38)-fold-change, upon treatment with compounds 3a, 3b,
3c, and 5a, respectively, assuring the apoptotic potentials. Finally, molecular docking also
greatly recommends the potential activity of the examined candidates (especially 3a and 3c)
against the GSTP1 receptor as a recommended mechanism for their antitumor activity.Conclusion:Our findings point to significant anticancer activities of Schiff bases tethered
OSe agents, suggesting their promising potential for development as effective anticancer
drugs.