Screening of novel carbohydrate-derived thioureas for antibacterial activity

Samson Lalhmangaihzuala Zathang Laldinpuii P. B. Lalthanpuii Zodinpuia Pachuau Khiangte Vanlaldinpuia Kholhring Lalchhandama   

Open Access   

Published:  Jun 07, 2024

DOI: 10.7324/JAPS.2024.180485

Compounds synthesized from carbohydrate substrates have yielded promising lead molecules for pharmaceutical developments, as many are approved for the clinical management of a wide range of diseases. Among them, thiourea moieties are the gold mines of antibacterial molecules. In view of the lack and need for new antibiotics, a series of 16 D-fructose-based thiourea compounds were synthesized from asymmetric aldol reaction and isopropylidenation. The new compounds were established from nuclear magnetic resonance, Fourier-transform infrared, and electrospray ionization mass spectrometry. Using disk diffusion assay for antibiotic susceptibility, four of the novel compounds were found to have concentration-dependent antibacterial activities. The addition of trifluoromethyl groups at the meta-position on the phenyl ring of the thioureas appeared to promote bacterial inhibitory action. Thiourea 2a exhibited the most potent activity against the Gram-negative species, Klebsiella pneumoniae, Escherichia coli, and Salmonella typhi, as well as the Gram-positive species, Micrococcus luteus; but not against all bacteria tested. Thiourea 2b and 3a had lower efficacy but showed better broad-spectrum activity against most bacteria tested. Thiourea 3b displayed species-specific activity only against K. pneumoniae and S. typhi. Our findings show the benefits and prospects of synthesizing new carbohydrate compounds for therapeutic medication.

Keyword:     Antibacterial activity bacteria carbohydrates synthesis thiourea


Lalhmangaihzuala S, Laldinpuii ZT, Lalthanpuii PB, Pachuau Z, Vanlaldinpuia K, Lalchhandama K. Screening of novel carbohydrate-derived thioureas for antibacterial activity. J Appl Pharm Sci. 2024. Online First.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text


1. Mendelson M, Sharland M, Mpundu M. Antibiotic resistance: calling time on the "silent pandemic". JAC Antimicrob Res. 2022;4(2):dlac016.

2. Lessa FC, Sievert DM. Antibiotic resistance: a global problem and the need to do more. Clin Infect Dis. 2023;77:S1-3.

3. Iskandar K, Murugaiyan J, Hammoudi Halat D, Hage SE, Chibabhai V, Adukkadukkam S, et al. Antibiotic discovery and resistance: the chase and the race. Antibiotics. 2022;11(2):182.

4. Bhattarai K, Bastola R, Baral B. Antibiotic drug discovery: challenges and perspectives in the light of emerging antibiotic resistance. Adv Genet. 2020;105:229-92.

5. Cook MA, Wright GD. The past, present, and future of antibiotics. Science Trans Med. 2022;14:7793.

6. Miethke M, Pieroni M, Weber T, Brönstrup M, Hammann P, Halby L, et al. Towards the sustainable discovery and development of new antibiotics. Nat Rev Chem. 2021;5(10):726-749.

7. Alén R. Carbohydrate chemistry: fundamentals and applications. New Jersey, USA: World Scientific; 2018, pp 1-5.

8. Boysen MMK. Carbohydrates: tools for stereoselective synthesis. Weinhelm, Germany: Wiley-VCH Verlag & Co.; 2012, pp 4-7, 19.

9. Su L, Feng Y, Wei K, Xu X, Liu R, Chen G. Carbohydrate-based macromolecular biomaterials. Chem Rev. 2021;121(18):10950-1029.

10. Sievenpiper JL. Low-carbohydrate diets and cardiometabolic health: the importance of carbohydrate quality over quantity. Nutr Rev. 2020; 78:S69-77.

11. Chandel NS. Carbohydrate metabolism. Cold Spring Harb Perspect Biol. 2021; 13(1):a040568.

12. Mishra N, Tiwari VK, Schmidt RR. Recent trends and challenges on carbohydrate-based molecular scaffolding: general consideration toward impact of carbohydrates in drug discovery and development. Carbohydrates in Drug Discovery and Development. Amsterdam, The Netherlands: Elsevier B.V.; 2020, pp 1-69.

13. Wang J, Wang D, Zhang Y, Dong J. Synthesis and biopharmaceutical applications of sugar-based polymers: new advances and future prospects. ACS Biomater Sci Eng. 2021;7(3):963-82.

14. Wang N, Kong Y, Li J, Hu Y, Li X, Jiang S, et al. Synthesis and application of phosphorylated saccharides in researching carbohydrate-based drugs. Bioorg Med Chem. 2022; 68:116806.

15. Pan L, Cai C, Liu C, Liu D, Li G, Linhardt RJ, et al. Recent progress and advanced technology in carbohydrate-based drug development. Curr Opin Biotechnol. 2021;69:191-98.

16. Wang PA, Feng JT, Wang XZ, Li MQ. A new class of glucosyl thioureas: synthesis and larvicidal activities. Molecules. 2016;21:925.

17. Zahra U, Saeed A, Fattah TA, Flörke U, Erben MF. Recent trends in chemistry, structure, and various applications of 1-acyl-3-substituted thioureas: a detailed review. RSC Adv. 2022; 12(20):12710-45.

18. Cunha S, MacEdo FC, Costa GAN, Rodrigues MT, Verde RBV, De Souza Neta LC, et al. Antimicrobial activity and structural study of disubstituted thiourea derivatives. Monatsh Chem. 2007;138:511-16.

19. Suresha GP, Suhas R, Kapfo W, Gowda DC. Urea/thiourea derivatives of quinazolinone-lysine conjugates: synthesis and structure-activity

relationships of a new series of antimicrobials. Euro J Med Chem. 2011;46:2530-40.

20. Qiao L, Huang J, Hu W, Zhang Y, Guo J, Cao W, et al. Synthesis, characterization, and in vitro evaluation and in silico molecular docking of thiourea derivatives incorporating 4-(trifluoromethyl) phenyl moiety. J Mol Struct. 2017;1139:149-59.

21. Vanlaldinpuia K, Bora P, Bez G. Monofunctional primary amine: a new class of organocatalyst for asymmetric aldol reaction. J Chem Sci. 2017;129:301-12.

22. Vanlaldinpuia K, Bez G. Useful methods for the synthesis of isopropylidenes and their chemoselective cleavage. Tetrahedron Lett. 2011;52:3759-64.

23. Bauer AW, Kirby WMM, Sherris JC, Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966;45:493-6.

24. CLSI. Performance Standards for Antimicrobial Disk Susceptibility Tests. 13th edition. Pasadena, USA: Clinical and Laboratory Standards Institute; 2018, pp 15-22.

25. Bielenica A, Stefanska J, Stepien K, Napiorkowska A, Augustynowicz-Kopec E, Sanna G, et al. Synthesis, cytotoxicity and antimicrobial activity of thiourea derivatives incorporating 3-(trifluoromethyl)phenyl moiety. Euro J Med Chem. 2015;101:111-25.

26. de Matos AM. Recent advances in the development and synthesis of carbohydrate-based molecules with promising antibacterial activity. Eur J Org Chem. 2023;26(4):e202200919.

27. Khan E, Khan S, Gul Z, Muhammad M. Medicinal importance, coordination chemistry with selected metals (Cu, Ag, Au) and chemosensing of thiourea derivatives. A review. Crit Rev Anal Chem. 2021;51(8):812-834.

28. Vázquez-Laslop N, Mankin AS. How macrolide antibiotics work. Trends Biochem Sci. 2018; 43:668-84.

29. Hutchings M, Truman A, Wilkinson B. Antibiotics: past, present and future. Curr Opin Microbiol. 2019;51:72-80.

30. Roemhild R, Bollenbach T, Andersson DI. The physiology and genetics of bacterial responses to antibiotic combinations. Nat Rev Microbiol. 2022;20(8):478-90.

31. Bonomo MG, Giura T, Salzano G, Longo P, Mariconda A, Catalano A, et al. Bis-thiourea quaternary ammonium salts as potential agents against bacterial strains from food and environmental matrices. Antibiotics. 2021;10(12):1466.

32. Tabor W, Katsogiannou A, Karta D, Andrianopoulou E, Berlicki ?, Vassiliou S, et al. Exploration of thiourea-based scaffolds for the construction of bacterial ureases inhibitors. ACS Omega. 2023;8(31):28783-96.

Article Metrics
115 Views 13 Downloads 128 Total



Related Search

By author names