Synthesis of Novel Donor-π-Acceptor Benzothiazole-Thiazolidinone Fluorescent Chromophores With Enhanced Biological Activity

Abstract

Four benzothiazole-thiazolidine-4-one derivatives 6 and 7a–c were prepared, and their chemical constructions were proved by IR, NMR, UV–Vis absorption, and emission spectra. The absorption spectra of the synthesized derivatives showed that extending the conjugated system through the insertion of a substituted benzylidene group led to a red shift of λ_max, where the nitro derivative 7c displayed the longer wavelength. Likewise, the emission spectra presented the same effect, where the Stock shift displayed a reversed order in which the parent 6 has the highest value. The synthesized derivatives exhibited cytotoxic effectiveness against several tumor cell lines, where compound 7b displayed significant cytotoxicity towards MCF-7 cells (IC₅₀ = 8.73 ± 0.41 μM). The in vitro VEGFR-2 kinase inhibitory activity of synthetic benzothiazole-thiazolidin-4-one derivatives has been assessed, where derivative 7c had the strongest inhibition (IC₅₀ = 0.20 ± 0.10 μM), followed by derivatives 7b and 7a, respectively. However, the molecular docking showed that derivatives 7b and 7c have higher binding affinity than Sorafenib due to unique molecular interactions with target residues. Moreover, the pharmacokinetic parameters of the newly synthesized derivatives showed that derivative 7b revealed moderate lipophilicity and a lack of Lipinski violations, making it a viable lead contender.