Synthesis, antiproliferative, and molecular docking of novel donor-π-acceptor benzothiazole conjugates based fluorescent chromophores

Abstract

Four targeting fluorescent 2-(N,N-dimethyl/diphenyl-aminophenyl)-5-substituted-benzothiazole conjugates 3a, 3b, 6a and 6b were synthesized. Insight into the photophysical characteristics of the synthesized conjugates, as well as measurements of absorbance and fluorescence maxima in diverse organic solvents, showed conjugate 3b ranged from 302 to 324 nm, whereas the fluorescence maxima ranged from 312 nm (CH2Cl2) to 465 nm. The conjugates' cytotoxicity was evaluated across anticancer cell lines, and the inhibitory action of these conjugates against VEGFR-2 was assessed using an antiphosphotyrosine antibody, with 3b and 6b conjugates showing potent cytotoxic activity against MCF-7 cells with IC50 values of 7.06 ± 0.29 and 8.82 ± 0.37 μM, respectively. Meanwhile, conjugate 6b had the greatest potency of the conjugates for VEGFR-2 inhibition, with an IC50 of 0.23 ± 0.20 μM. Though the binding’s interactions were stimulated using molecular docking, A higher binding score and a variety of interaction types for conjugate 3b, temporarily, indicated a stronger interaction. Moreover, the ADME study was performed and showed that conjugates 3b and 6b exhibited enhanced lipophilicity and reduced solubility, which may influence their pharmacokinetic behavior.