Design, synthesis, DNA binding, modeling, anticancer studies and DFT calculations of Schiff bases tethering benzothiazole-1,2,3-triazole conjugates

In an attempt to design and prepare a new library of anticancer candidates, focused thiopropargylated benzothiazole was reacted with ethyl azidoacetate and/or ethyl azidobenzoate to yield newer 1,2,3-triazole-benzothiazole conjugates bearing ester functionality through click chemistry approach. The hydrazinolysis of the obtained ester-based triazoles was also carried out to give the corresponding 1,2,3-triazole acid hydrazide derivatives as precursors for the synthesis of the focused Schiff bases by their condensation with various benzaldehyde derivatives. Spectroscopic study was investigated on the establishment of the structures of all newly synthesized Schiff bases bearing benzothiazole-1,2,3-triazole molecular conjugate. The newly designed hydrazones showed two isomers ( cis-E and trans-E ) with different isomeric distribution as confirmed by NMR spectral data and supported by DFT carried out in gas phase at B3LYP 6-311G (d,p) basis set. The DFT results showed that the cis-E isomer is the lower energy structure and this finding was illustrated in terms of the intermolecular H-bonding. These molecules were screened for anticancer activities with A549 and H1299 lung cancer cell lines. The anticancer activities ranged from 55 to 90%. DNA binding study was also carried out to see the mechanism of action and the DNA binding constants were of good value ranging from of 2.0 x 10(5) and 14.7 x 10(5) M-1; indicating good interactions of the reported molecules with DNA. Finally, the modeling was confirmed and it was found that the results of modeling were in good agreement with the results of anticancer and DNA binding studies. All these finding confirmed that the reported molecules work as anticancer agents by interacting with DNA. (C) 2020 Published by Elsevier B.V.

Automated summary

In an attempt to design and prepare a new library of anticancer candidates, novel 1,2,3-triazole-benzothiazole conjugates were synthesized through click chemistry, and Schiff bases with potential anticancer activity were successfully prepared. The molecules showed good interactions with DNA, as indicated by the DNA binding constants, and exhibited promising anticancer activities against lung cancer cell lines. The modeling results were in agreement with the experimental findings, confirming the potential of the synthesized molecules as effective anticancer agents.