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Synthesis, Characterization and Antibacterial Evaluation of some New 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines as Potential Antibacterial Agents

[ Vol. 15 , Issue. 7 ]

Author(s):

Kooi-Mow Sim* and Kah-Cheng Teo   Pages 733 - 743 ( 11 )

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.

Keywords:

1, 2, 4-Triazole, fusion, indole, triazolothiadiazine, antibacterial, MRSA, MSSA.

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

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