Title:Synthesis, Characterization and Antibacterial Evaluation of some New 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines as Potential Antibacterial Agents
VOLUME: 15 ISSUE: 7
Author(s):Kooi-Mow Sim* and Kah-Cheng Teo
Affiliation:Centre for Biodiversity Research, University Tunku Abdul Rahman, Jalan Universiti, Jalan Barat, Kampar 31900, Perak, Centre for Biodiversity Research, University Tunku Abdul Rahman, Jalan Universiti, Jalan Barat, Kampar 31900, Perak
Keywords:1, 2, 4-Triazole, fusion, indole, triazolothiadiazine, antibacterial, MRSA, MSSA.
Abstract:Background: Indole derivatives and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines are important
heterocyclic compounds in medicinal chemistry. They have displayed broad spectrum of biological
activities such as anticancer, antimicrobial, antioxidant and anti-inflammatory activities.
Objective: The objectives of this research were to synthesize 4-amino-5-mercapto-3-[(5-substituted-
2-methyl-1H-indol-3-yl)methyl]-1,2,4-triazoles and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines incorporating
an indole skeleton and to evaluate their antibacterial activity.
Methods: 4-Amino-5-mercapto-3-[(5-substituted-2-methyl-1H-indol-3-yl)methyl]-1,2,4-triazoles were
synthesized from the fusion reaction of 5-substituted-2-methylindole-3-acetic acids with thiocarbohydrazide.
The reaction of 4-amino-5-mercapto-3-[(5-substituted-2-methyl-1H-indol-3-yl)methyl]-
1,2,4-triazoles with a series of phenacyl bromides produced the corresponding 1,2,4-triazolo[3,4-
b][1,3,4]thiadiazines. The structures of 1,2,4-triazoles and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines
were elucidated by IR, NMR and mass spectral data and were evaluated for their antibacterial activity
using 96-well microbroth dilution assay.
Results: In the current study, two new 4-amino-5-mercapto-3-[(5-substituted-2-methyl-1H-indol-3-
yl)methyl]-1,2,4-triazoles (2b-c) and twenty four new 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines incorporating
an indole skeleton (3a-h, 4a-h and 5a-h) have been synthesized.
Conclusion: Compound 4d bearing chlorinated indole moiety and 4-methylphenyl group at C-6
position of triazolothiadiazine ring showed promising inhibition activity against Bacillus subtilis
subsp. spizizenni, Bacillus cereus and Staphylococcus aureus with MIC value 3.91 µg/ml. Compound
4d also exhibited promising activity against MRSA ATCC 29213 at MIC 7.81 µg/ml.
