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 1H NMR, 13C 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.
| Published in | Advances in Biochemistry (Volume 9, Issue 4) |
| DOI | 10.11648/j.ab.20210904.12 |
| Page(s) | 98-105 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
Triazole-Pyrimidine, SecA Inhibitor, Small Molecule, Antimicrobial, Target, Drug-resistant
| [1] | Rice LB (2009) The clinical consequences of antimicrobial resistance. Curr Opin Microbiol 12 (5): 476-481. |
| [2] | Smets D, Loos MS, Karamanou S, Economou A (2019) Protein Transport Across the Bacterial Plasma Membrane by the Sec Pathway. Protein J 38 (3): 262-273. |
| [3] | Kusters I, Driessen AJ (2011) SecA, a remarkable nanomachine. Cell Mol life Sci 68: 2053-2066. |
| [4] | Hsieh YH, Zhang H, Lin BR, Cui N, Na B, Yang H, Jiang C, Sui SF, Tai PC (2011) SecA Alone Can Promote Protein Translocation and Ion Channel Activity: SecYEG increases efficiency and signal peptide specificity. J Biol Chem 286: 44702-44709. |
| [5] | Banerjee T, Zheng Z, Abolafia J, Harper S, Oliver D (2017) The SecA protein deeply penetrates into the SecYEG channel during insertion, contacting most channel transmembrane helices and periplasmic regions. J Biol Chem 292: 19693-19707. |
| [6] | Findik BT, Smith VF, Randall LL. (2018) Penetration into membrane of amino-terminal region of SecA when associated with SecYEG in active complexes. Protein Sci 27: 681-691. |
| [7] | Cranford-Smith T, Huber D (2018) The way is the goal: how SecA transports proteins across the cytoplasmic membrane in bacteria. FEMS Microbiol Lett 365. |
| [8] | Ma C, Wu X, Sun D, Park E, Catipovic MA, Rapoport TA, Gao N, Li L (2019) Structure of the substrate-engaged SecA-SecY protein translocation machine. Nat Commun 10: 2872. |
| [9] | Gupta R, Toptygin D, Kaiser CM (2020) The SecA motor generates mechanical force during protein translocation. Nat Commun 11: 3802. |
| [10] | Rao CVS, De Waelheyns E, Economou A, Anné J (2014) Antibiotic targeting of the bacterial secretory pathway. Biochim Biophys Acta 1843 (8): 1762-1783. |
| [11] | Chaudhary AS, Chen W, Jin J, Tai PC, Wang B (2015) SecA: a potential antimicrobial target. Future Med Chem 7 (8): 989-1007. |
| [12] | Jin J, Hsieh YH, Chaudhary AS, Cui J, Houghton JE, Sui SF, Wang B, Tai PC (2018) SecA inhibitors as potential antimicrobial agents: differential actions on SecA-only and SecA-SecYEG protein-conducting channels. FEMS Microbiol Lett 365 (15): fny 145. |
| [13] | Catipovic MA, Bauer BW, Loparo JJ, Rapoport TA (2019) Protein translocation by the SecA ATPase occurs by a power-stroke mechanism. EMBO J 38 (9): e101140. |
| [14] | Chen W, Huang YJ, Gundala SR, Yang H, Li M, Tai PC, Wang B (2010) The first low microM SecA inhibitors. Bioorg Med Chem 18 (4): 1617-1625. |
| [15] | Cui J, Jin J, Hsieh YH, Yang H, Ke B, Damera K, Tai PC, Wang B (2013) Design, Synthesis and Biological Evaluation of Rose Bengal Analogues as SecA Inhibitors. ChemMedChem 8 (8): 1384-1393. |
| [16] | Li M, Huang YJ, Tai PC, Wang B (2008) Discovery of the first SecA inhibitors using structure-based virtual screening. Biochem Biophys Res Commun 368 (4): 839-845. |
| [17] | Chaudhary AS, Jin J, Chen W, Tai PC, Wang B (2015) Design, syntheses and evaluation of 4-oxo-5-cyano thiouracils as SecA inhibitors. Bioorg Med Chem 23: 105-117. |
| [18] | Jang MY, De Jonghe S, Segers K, Anné J, Herdewijn P (2011) Synthesis of novel 5-amino-thiazolo[4,5-d]pyrimidines as E. coli and S. aureus SecA inhibitors. Bioorg Med Chem 19 (1): 702-714. |
| [19] | Akula N, Trivedi P, Han FQ, Wang N (2012) Identification of small molecule inhibitors against SecA of Candidatus Liberibacter asiaticus by structure based design. Eur J Med Chem 54: 919-924. |
| [20] | Akula N, Zheng H, Han FQ, Wang N (2011) Discovery of novel SecA inhibitors of Candidatus Liberibacter asiaticus by structure based design. Bioorg Med Chem Lett 21 (14): 4183-4188. |
| [21] | Bamba F, Jin J, Chaudhary AS, Tai PC, Wang B (2021) Design, synthesis, and biological evaluation of pyrimidine analogs as SecA inhibitors. Med Chem Res 30: 1334-1340. |
| [22] | Bamba F, Jin J, Tai PC, Wang B (2020) Synthesis and biological evaluation of novel 4-oxo-5-cyano thiouracil derivatives as SecA inhibitors. Heterocyc Commun 26: 76-83. |
| [23] | Eswaran S, Adhikari AV, Shetty NS (2009) Synthesis and antimicrobial activities of novel quinoline derivatives carrying 1,2,4-triazole moiety. Eur J Med Chem 44: 4637-4647. |
| [24] | Schneider P, Hawser S, Islam K (2003) Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. Bioorg Med Chem Lett 13: 4217-4221. |
| [25] | Barot KP, Manna KS, Ghate MD (2017) Design, synthesis and antimicrobial activities of some novel 1,3,4-thiadiazole, 1,2,4-triazole-5-thione and 1,3-thiazolan-4-one derivatives of benzimidazole. Journal of Saudi Chemical Society 21: S35-S43. |
| [26] | Smith J, Andes D (2008) Therapeutic drug monitoring of antifungals: pharmacokinetic and pharmacodynamic considerations. Therapeutic drug monitoring 30: 167-172. |
| [27] | Afreen F, Chakraborty R, Thakur A (2015) Synthesis of a triazole derivative and evaluation of their antituberculer activity. Int J Pharmaceut Chem 5: 343-349. |
| [28] | Pandey V, Tusi Z, Tusi S, Joshi M (2012) Synthesis and biological evaluation of some novel 5-[(3-aralkyl amido/imidoalkyl) phenyl]-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines as antiviral agents. ISRN Org Chem 2012: 760517. https://doi.org/10.5402/2012/760517. |
| [29] | De Clercq E (2004) Antiviral drugs in current clinical use. J Clin Virol 30: 115-133. |
| [30] | Sharma V, Chitranshi N, Agarwal AK (2014) Significance and biological importance of pyrimidine in the microbial World. Int J Med Chem 2014: 202784. doi: 10.1155/2014/202784. |
| [31] | Kaur P, Chawla A (2017) 1,2,4-triazole: a review of pharmacological activities. Int Res J Pharm 8: 10-29. |
| [32] | Cui J, Jin J, Chaudhary AS, Hsieh YH, Zhang H, Dai C, Damera K, Chen W, Tai PC, Wang B (2016) Design, synthesis and evaluation of triazole-pyrimidine analogues as SecA inhibitors. ChemMedChem. 11 (1): 43-56. doi: 10.1002/cmdc.201500447. |
| [33] | Nakane A, Takamatsu H, Oguro A, Sadaie Y, Nakamura K, Yamane K (1995) Acquisition of azide-resistance by elevated SecA ATPase activity confers azide-resistance upon cell growth and protein translocation in Bacillus subtilis. Microbiology 141: 113-21. |
| [34] | Plech T, Wujec M, Siwek A, Kosikowska U, Malm A (2011) Synthesis and antimicrobial activity of thiosemicarbazides, s-triazoles and their Mannich bases bearing 3-chlorophenyl moiety. Eur J Med Chem 46 (1): 241-248. |
| [35] | Leysen D, Defert O, Kaval N, Blom P, Boland S (2011) Heterocyclic amides as rock inhibitors. WO2011107608A1. |
| [36] | Sommer WJ, Weck M (2007) Facile functionalization of gold nanoparticles via microwave-assisted 1,3 dipolar cycloaddition. Langmuir 23 (24): 11991-11995. doi: 10.1021/la7018742. |
| [37] | Patil SS, Jadhav RP, Patil AA, Patil SV, Bobade VD (2010) J Chem Pharm Res 2: 38 – 51. |
| [38] | Fresno N, Macías-González M, Torres-Zaguirre A, Romero-Cuevas M, Sanz-Camacho P, Elguero J, Pavón J, Rodríguez de Fonseca F, Goya P, Pérez-Fernández R (2015) Novel Oxazolidinone-Based Peroxisome Proliferator Activated Receptor Agonists: Molecular Modeling, Synthesis, and Biological Evaluation. J Med. Chem 58 (16): 6639–6652. |
| [39] | Li K, Chen Y, Li S, Nguyen HG, Niu Z, You S, Mello CM, Lu X, Wang Q (2010) Chemical Modification of M13 Bacteriophage and Its Application in Cancer Cell Imaging. Bioconjugate Chem 21 (7): 1369-1377. |
APA Style
Fanté Bamba, Camara Tchambaga Etienne, Coulibali Sioménan, Akpa Sagne Jacques, Coulibaly Souleymane, et al. (2021). Design, Synthesis and Antibacterial Activities of Triazole-Pyrimidine Derivatives as SecA Inhibitors. Advances in Biochemistry, 9(4), 98-105. https://doi.org/10.11648/j.ab.20210904.12
ACS Style
Fanté Bamba; Camara Tchambaga Etienne; Coulibali Sioménan; Akpa Sagne Jacques; Coulibaly Souleymane, et al. Design, Synthesis and Antibacterial Activities of Triazole-Pyrimidine Derivatives as SecA Inhibitors. Adv. Biochem. 2021, 9(4), 98-105. doi: 10.11648/j.ab.20210904.12
AMA Style
Fanté Bamba, Camara Tchambaga Etienne, Coulibali Sioménan, Akpa Sagne Jacques, Coulibaly Souleymane, et al. Design, Synthesis and Antibacterial Activities of Triazole-Pyrimidine Derivatives as SecA Inhibitors. Adv Biochem. 2021;9(4):98-105. doi: 10.11648/j.ab.20210904.12
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Download@article{10.11648/j.ab.20210904.12,
author = {Fanté Bamba and Camara Tchambaga Etienne and Coulibali Sioménan and Akpa Sagne Jacques and Coulibaly Souleymane and Adjou Ané},
title = {Design, Synthesis and Antibacterial Activities of Triazole-Pyrimidine Derivatives as SecA Inhibitors},
journal = {Advances in Biochemistry},
volume = {9},
number = {4},
pages = {98-105},
doi = {10.11648/j.ab.20210904.12},
url = {https://doi.org/10.11648/j.ab.20210904.12},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ab.20210904.12},
abstract = {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 1H NMR, 13C 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.},
year = {2021}
}
TY - JOUR T1 - Design, Synthesis and Antibacterial Activities of Triazole-Pyrimidine Derivatives as SecA Inhibitors AU - Fanté Bamba AU - Camara Tchambaga Etienne AU - Coulibali Sioménan AU - Akpa Sagne Jacques AU - Coulibaly Souleymane AU - Adjou Ané Y1 - 2021/11/23 PY - 2021 N1 - https://doi.org/10.11648/j.ab.20210904.12 DO - 10.11648/j.ab.20210904.12 T2 - Advances in Biochemistry JF - Advances in Biochemistry JO - Advances in Biochemistry SP - 98 EP - 105 PB - Science Publishing Group SN - 2329-0862 UR - https://doi.org/10.11648/j.ab.20210904.12 AB - 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 1H NMR, 13C 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. VL - 9 IS - 4 ER -
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