Triphenylamine-Thiophene Donor-π-Acceptor Chromophores: Synthesis, Photophysical Properties, TD-DFT Analysis, and Anticancer Potential.

The present work reports the synthesis of novel D-π-A chromophores based on the molecular architecture of triphenylamine (donor group), thiophene (conjugated bridge) and aryl-methanimine (acceptor group). The synthetic route for the target chromophores involved the condensation of 2-formyl-5-(4-(diphenylamino)styryl)thiophene (5) with the appropriate acceptor, either 4-cyanoaniline or 4-nitroaniline (TPAT-CN and TPAT-NO2), respectively. The newly synthesized chromophores were characterized by absorption and fluorescence spectroscopy, as well as other spectral data. The absorption and emission spectra of the chromophores were recorded in DMSO and presented a good Stokes' shift ([Formula: see text] = 5505-5593 cm-1). The FMOs patterns and energies, obtained from DFT calculations, for the solvated ground (So) and excited states (S1) have been compared. Moreover, the in vitro cytotoxic activity of the chromophores has been examined against three human cancer cell lines and a human fibroblast line (WI38), using Sorafenib as a reference. The TPAT-CN chromophore displayed strong cytotoxic effectiveness towards HCT-116 and HepG2 cells (IC50 = 6.25 ± 0.36 and 9.44 ± 0.05 µM), while the TPAT-NO₂ analogue exhibited moderate effectiveness across the investigated cancer cells. In addition, the VEGFR-2 kinase inhibition efficacy revealed that both chromophores effectively inhibited VEGFR-2 enzymatic activity in the sub-micromolar range, where TPAT-CN IC50 = 0.53 ± 0.26 µM and TPAT-NO2 IC50 = 0.62 ± 0.11 µM. Finally, the molecular docking study was conducted against the VEGFR-2 receptor (PDB: 3WZE) and revealed promising binding affinity, superior Sorafenib.