Background: :
Thiadiazole not only acts as “hydrogen binding domain” and “two-electron donor
system” but also as constrained pharmacophore.
Methods::
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 involves 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 was 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.
Results: :
The DSC study clearly showed that the compound 4-maleate salt is crystalline in nature. In vitro
antibacterial inhibition and little potential for DNA cleavage of the compound 4 were explored. We extended
our study to explore the inhibition mechanism by conducting molecular docking, ADMET and molecular
dynamics analysis by using Schrödinger. The molecular docking for compound 4 showed better interactions
with target 3IVX with docking score of -8.508 kcal/mol with respect to standard ciprofloxacin (docking
score= -3.879 kcal/mol). TML-Hydroxy was obtained in silico as non-carcinogenic and non-AMES
toxic with good percent human oral absorption profile (69.639%). TML-Hydroxy showed the moderate inhibition
against Mycobacteria tuberculosis with MIC 25.00 μg/mL as well as moderate inhibition against S.
aureus, Bacillus sps, K. Pneumoniae and E. coli species.
Conclusion: :
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.
IN SILICO STUDY OF THE ANTIMICROBIAL PROFILE OF β-CITRONELLOL: POTENTIAL AS AN ANTIFUNGAL