In silico appraisal, Synthesis, Antibacterial screening and DNA cleavage for 1,2,5-thiadiazole derivative.

The maleate salt of 2-((2-hydroxy-3-((4-morpholino-1,2,5-thiadiazol-3-yl) oxy) propyl) amino)-2-methylpropan-1-ol (TML-Hydroxy)(4) has been synthesized. This methodology involve preparation of 4-morpholino-1,2,5-thiadiazol-3-ol by hydroxylation of 4-(4-chloro-1,2,5-thiadiazol-3-yl) morpholine followed by condensation with 2-(chloromethyl) oxirane to afford 4-(4-(oxiran-2-ylmethoxy)-1,2,5-thiadiazol-3-yl) morpholine. Oxirane ring of this compound opened by treating with 2-amino-2-methyl propan-1-ol to afford the target compound TML-Hydroxy. Structures of the synthesized compounds have been elucidated by NMR, MASS, FTIR spectroscopy. In vitro antibacterial inhibition and little DNA cleavage potential of the compound explored. We extended our study to explore the inhibition mechanism by conducting molecular docking, ADMET and molecular dynamics analysis by using Schrödinger. TML-Hydroxy showed the moderate inhibition against Mycobacteria tuberculosis with MIC 25.00 μg/mL. In view of the importance of the 1,2,5-thiadiazole moiety involved, this study would pave the way for future development of more effective analogs for applications in medicinal field.