In Silico Appraisal, Synthesis, Antibacterial Screening and DNA Cleavage for 1,2,5-thiadiazole Derivative

(E-pub Ahead of Print)

Author(s): Suraj N. Mali, Sudhir Sawant, Hemchandra K. Chaudhari*, Mustapha C. Mandewale.

Journal Name: Current Computer-Aided Drug Design

Become EABM
Become Reviewer

Abstract:

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.

Keywords: heterocycle, tuberculosis, DNA cleavage, molecular docking, thiadiazole, antibacterial.

Rights & PermissionsPrintExport Cite as


Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1573409915666190206142756
Price: $95

Article Metrics

PDF: 7