Microwave-assisted Synthesis of Novel Mannich Base and Conazole Derivatives Containing Biologically Active Pharmacological Groups

Author(s): Yıldız Uygun Cebeci*, Sule Ceylan, Neslihan Demirbas, Şengül Alpay Karaoğlu

Journal Name: Letters in Drug Design & Discovery

Volume 18 , Issue 3 , 2021


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Abstract:

Background: The aim of this study was to synthesize new mannich bases and conazol derivatives with biological activity by the microwave-assisted method.

Introduction: 1,2,4-Triazole-3-one (3) acquired from tryptamine was transformed to the corresponding carbox(thio)amides (6a-c) via several steps. Compounds 6a-c were refluxed with sodium hydroxide to yield 1,2,4-triazole derivatives (7a-c). Compounds 3 and 7a-c on treatment with different heterocyclic secondary amines in an ambiance with formaldehyde afforded the mannich bases 8-15 having diverse pharmacophore units with biologically active sites. The reaction of compound 3 and 2-bromo-1-(4-chlorophenyl) ethanone in the presence of sodium ethoxide gave the corresponding product 2-substituted-1,2,4-triazole-3-one, 16, which was reduced to 1,2,4-triazoles (17). Synthesis of compounds 18, 19, and 20 was carried out starting from compounds 17 with 4-chlorobenzyl chloride (for 18), 2,4-dichlorobenzyl chloride (for 19), and 2,6-dichlorobenzyl chloride (for 20).

Methods: The conventional technique was utilized for the synthesis of compounds, 3-7, and microwave- assisted technique for the compounds, 8-20. That is, green chemistry techniques were applied during these reactions. The structures of molecules were elucidated on the foundation of 1H NMR, 13C NMR, FT-IR, EI-MS methods, and elemental analysis. Novel synthesized molecules were investigated for their antimicrobial activity using MIC (minimum inhibitory concentration) method.

Results: Aminoalkylation of triazole derivatives 3 and 7a-c with fluoroquinolones such as ciprofloxacin and norfloxacin provided an enhancement to the bioactivity of mannich bases 8-11 against the tested microorganisms. The MIC values ranged between <0.24 and 3.9 μg/mL. Moreover, molecules 10 and 11 exhibited more effects on M. smegmatis than the other compounds by the MIC values of <1 μg/mL. They have shown very good antituberculosis activity.

Conclusion: Most of the synthesized structures were observed to have excellent antimicrobial activity against most microorganisms taken into account. These molecules have better activity than the standard drug ampicillin and streptomycin.

Keywords: 1, 2, 4-triazole, tryptamine, mannich, conazole, antimicrobial activity, antituberculosis activity.

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Article Details

VOLUME: 18
ISSUE: 3
Year: 2021
Published on: 19 April, 2021
Page: [269 - 283]
Pages: 15
DOI: 10.2174/1570180817999201016154034
Price: $65

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