Microwave-assisted synthesis of novel mannich base and conazole derivatives containing biologically active pharmacological groups
Letters in Drug Design and Discovery, cilt.18, sa.3, ss.269-283, 2021 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 18 Sayı: 3
- Basım Tarihi: 2021
- Doi Numarası: 10.2174/1570180817999201016154034
- Dergi Adı: Letters in Drug Design and Discovery
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE
- Sayfa Sayıları: ss.269-283
- Anahtar Kelimeler: 1,2,4-triazole, tryptamine, mannich, conazole, antimicrobial activity, antituberculosis activity
- Kırklareli Üniversitesi Adresli: Evet
Özet
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.