Microwave versus conventional synthesis, anticancer, DNA binding and docking studies of some 1,2,3-triazoles carrying benzothiazole

Abstract

The present work describes the synthesis of new click products with a 2-mercapto-benzothiazole basic structure supporting the different functionalized side chains linked to the 1,2,3-triazole ring at position N-1 via Cu(I)-mediated click chemistry under both thermal and microwave irradiation (MWI). MWI led to higher yields in much less time than classical methods. The obtained click adducts were fully characterized using different spectroscopic experiments including IR, 1H NMR, 13C NMR and high-resolution mass spectrometry, and assessed for their anticancer activities. The maximum anticancer activities were found to be 90% of the compounds 5d and 5h with A549 and H-1229 lung cancer cell lines. The DNA binding constants of the most active compounds of 5d and 5h were 4.7 × 105 and 10.2 × 105 M−1, respectively; confirming the interactions with DNA. The anticancer mechanism was determined by the modeling studies with DNA and the binding energies of the compounds of 5d and 5h were −5.1 and −5.0 kcal mol−1; confirming the DNA binding experimental results. Finally, it was found that almost all the compounds showed good anticancer activities at 400 µg/mL concentration but the compounds 5d and 5h may be potentially anticancer candidates.

Keywords

• Synthesis of benzothiazole
• 1,2,3-triazole
• Molecular hybridization
• Anticancer activities
• DNA binding
• DNA docking