CuAAC Mediated Synthesis of 2‐HBT Linked Bioactive 1,2,3‐Triazole Hybrids: Investigations through Fluorescence, DNA Binding, Molecular Docking, ADME Predictions and DFT Study

• Published in: ChemistrySelect (Weinheim) 2021-01, Vol.6 (4), p.685-694
• Main Authors: Nehra, Nidhi, Kumar Tittal, Ram, Ghule, Vikas D., Kumar, Nikhil, Kumar Paul, Avijit, Lal, Kashmiri, Kumar, Ashwini
• Format: Article
• Language: English
• Subjects: 2-alkoxyphenyl benzothiazole- 1,2,3-triazole; Alkyl spacers; DFT study; DNA recognition; Fluorescence
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202003919

A series of three different classes of benzothiazole linked 1,2,3‐triazole hybrid molecules with varying alkyl spacers (ethyl, propyl, and butyl) between 2‐hydroxyphenyl benzothiazoles and 1,2,3‐triazoles are efficiently synthesized under CuAAC condition. All compounds are satisfactorily characterized by FTIR, 1H‐NMR, 13C‐NMR, ESI‐MS data and structures of some compounds were finally supported by single‐crystal X‐ray diffraction data. Most of the synthesized compounds exhibited good to better DNA binding property (0.28×105 M−1 to 2.91×105 M−1) and well drug‐like properties. Some promising compounds showed good agreement to all experimental and theoretical computed properties (fluorescence study, DNA binding, molecular docking, DFT, and ADME Predictions). A new series of 2‐hydroxyphenyl benzothiazoles (2‐HBT) linked 1,2,3‐triazoles were efficiently synthesized under CuAAC condition and all were fully characterized. The effect of varying alkyl linkers between 2‐HBT and 1,2,3‐triazoles on fluorescence, DNA binding, molecular docking, chemical reactivity, and drug‐like properties were explored. All synthesized compounds exhibited good to high DNA binding property, except one. Three most promising compounds showed good agreement of wet DNA binding experimental with theoretical results of molecular docking and DFT study.