Purpose: To investigate the antibacterial and α-glucosidase inhibitory activities of hydrazone
derivatives (
8a-h) of ethyl isonipecotate.
Methods: The reaction of ethyl isonipecotate (
2) with 3,5-dichloro-2-hydroxybenzenesulfonyl chloride
(
1) in an aqueous basic medium yielded ethyl 1-[(3,5-dichloro-2-hydroxyphenyl)sulfonyl]piperidin-4-carboxylate (
3). Compound
3 was subsequently converted to ethyl 1-[(3,5-dichloro-2-ethoxyphenyl)sulfonyl]piperidin-4-carboxylate (5) via O-alkylation. Compound
5 on reaction with
hydrated hydrazine yielded 1-[(3,5-dichloro-2-ethoxyphenyl)sulfonyl]piperidin-4-carbohyrazide (
6) in
MeOH. Target compounds
8a-h were synthesized by stirring 6 with different aromatic aldehydes (
7a-h)
in MeOH. All the synthesized compounds were structurally elucidated by proton nuclear magnetic
resonance (1H-NMR), electron impact mass spectrometry (EI-MS) and infrared (IR) spectroscopy. For
antibacterial activity, solutions of the synthesized compounds were mixed with bacterial strains, and the
change in absorbance before and after incubation was determined. For enzyme inhibitory activity,
change in the absorbance of mixtures of synthesized compounds and enzyme before and after
incubation with substrate was determined.
Results: The target compounds were synthesized in appreciable yields and well characterized by
spectral data analysis.
Salmonella typhi
was inhibited by
8e (MIC 8.00 ± 0.54 μM),
Escherichia coli
by
8f
(8.21 ± 0.83 μM),
Bacillus subtilis
by
8c (8.56 ± 0.63 μM) and
Staphylococcus aureus
by
8c (8.86 ± 0.29
μM). Two compounds,
8e and
8d, were very effective inhibitors of α-glucosidase with IC
50 values of
40.62 ± 0.07 and 48.64 ± 0.08 μM, respectively.
Conclusion: Low IC
50 values of the synthesized compounds against α-glucosidase demonstrates their
potential in type-2 diabetes treatment. Furthermore, these compounds exhibit substantial antibacterial
activity against the bacterial strains tested.
