Design, synthesis, and biological evaluation of pyrimidine analogs as SecA inhibitors

Bamba, Fanté; Jin, Jinshan; Chaudhary, Arpana S.; Tai, Phang C.; Wang, Binghe

doi:10.1007/s00044-021-02717-6

Cited by 5 publications

(3 citation statements)

References 24 publications

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“…Moreover, Biginelli in 1893, synthesized 2-thiopyrimidines [16] which demonstrated several pharmaceutical properties. The 2-thiopyrimidines was found to have excellent antimicrobial [17] [18] [19], antiviral [20], anti-inflammatory [21] and antitumor [22] properties. Therefore, 2-thiopyrimidines gained more attention from worldwide organic chemists [23].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antibacterial Activities of New 2-(Benzylthio)pyrimidines and 2-(Benzimidazolylmethylthio)pyrimidines Derivatives

Achi¹,

Coulibali²,

Zon³

et al. 2021

OJMC

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A series of 2-(benzylthio)pyrimidines (6a-l) and 2-(benzimidazolylmethylthio)pyrimidines derivatives (6m and 6n) analogues of ethyl 2-(benzylthio)-6-methyl-4-phenyl-1,4-dihydropyrimidine-5-carboxylates and ethyl 2-(((1H-benzimidazol-2-yl)methyl)thio)-6-methyl-4-phenyl-1,4-dihydropyri-midine-5-carboxylates were prepared and evaluated for antibacterial activity. These compounds were obtained by condensation of 2-thiopyrimidines (4) with benzyl halides or 2-(chloromethyl)-1H-benzimidazole (5) in the presence of a base. All compounds were characterized by 1 H, 13 C and HRMS spectra. Out of fourteen, only eight compounds were screened against multi-resistant strains of Escherichia coli and Staphylococcus aureus. The results revealed that all of them were found to possess significant antibacterial activity against the germs tested. Compounds 6c, 6d, 6h and 6m were more active on S. aureus and compounds 6h and 6m more active on E. coli.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Antibacterial Activities of New 2-(Benzylthio)pyrimidines and 2-(Benzimidazolylmethylthio)pyrimidines Derivatives

Achi¹,

Coulibali²,

Zon³

et al. 2021

OJMC

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“…[2,11,13] Currently, small organic molecules described in the literature as SecA inhibitors mainly include Rose Bengal, [14] bisthiouracil, [15] bistriazole [16] and their derivatives, [17] thiazolo [4,5-d]pyrimidine derivatives [18] and others. [ [19][20][21][22] In order to nd new SecA inhibitors, it is worthwhile to explore the chemistry space of known inhibitor to increase structural diversity.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Antibacterial Activities of Triazole-pyrimidine Derivatives as SecA Inhibitors

Bamba

Camara

Coulibali

et al. 2021

Preprint

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SecA, a key component of bacterial Sec-dependent secretion pathway, is an attractive target for exploring novel antimicrobials. Along this line, we reported optimization of a hit bistriazole (SCA 21) which has been previously identified as a SecA inhibitor. Herein we describe the synthesis of some novel triazole-pyrimidine derivative by structural modification of SCA 21. Some of them have been evaluated for their antimicrobial activity against against Escherichia coli NR698 (a leaky mutant), Staphylococcus aureus and Bacillus anthracis Sterne.

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“…From this perspective, our goal as scientists became to work in the field of targeting SecA, which is a critical protein secretion machinery indispensable for bacterial survival [2,11,13]. Currently, most of the small organic molecules reported in the literature as SecA inhibitors essentially include bisthiouracil [14], Rose Bengal [15], bistriazole [16] and their derivatives [17], thiazolo [4,5-d]pyrimidine derivatives [18] and others [19][20][21][22]. To go further than what is already known about SecA small molecules, we will explore the chemistry space to increase structural diversity in their scaffold for the development of new SecA inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Antibacterial Activities of Triazole-Pyrimidine Derivatives as SecA Inhibitors

Bamba¹,

Etienne²,

Coulibali³

et al. 2021

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Background: To highlight the magnitude of the important challenge now facing scientists, drug resistance needs exploration of novel antimicrobial agents. The identification of new and vital target in bacteria and then designing their inhibitors can be explored. Thus, targeting SecA, a central component of the bacterial general secretion system, is a promising strategy for the development of novel antimicrobials. Objective: To evaluate new compounds as SecA inhibitors synthesized by structural modification of bistriazole SCA-21. Method: A new compounds were synthesized and evaluated for antibacterial activity against Escherichia coli NR698 (E. coli a leaky mutant), Staphylococcus aureus (S. aureus) and Bacillus anthracis (B. anthracis). Results: Some novel triazole-pyrimidine derivatives by structural modification of known SecA inhibitor SCA 21 were synthesized and their structures were confirmed by 1 H NMR, 13 C NMR and Mass spectral analysis. The synthesized compound showed antimicrobial activity against E. coli NR698 (a leaky mutant), S. aureus and B. anthracis Sterne. Conclusion: Five novel triazole-pyrimidine derivatives were designed, synthesized and evaluated as SecA inhibitors. At the end of this study, compound SCA 259 with azide pentyl group was found as the most potent inhibitor. It expressed better inhibitory activity against SecA ATPase than else known inhibitor SCA 21.

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Design, synthesis, and biological evaluation of pyrimidine analogs as SecA inhibitors

Cited by 5 publications

References 24 publications

Synthesis and Antibacterial Activities of New 2-(Benzylthio)pyrimidines and 2-(Benzimidazolylmethylthio)pyrimidines Derivatives

Synthesis and Antibacterial Activities of New 2-(Benzylthio)pyrimidines and 2-(Benzimidazolylmethylthio)pyrimidines Derivatives

Design, Synthesis and Antibacterial Activities of Triazole-pyrimidine Derivatives as SecA Inhibitors

Design, Synthesis and Antibacterial Activities of Triazole-Pyrimidine Derivatives as SecA Inhibitors

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