Antibacterials

Antibacterials, Medicinal chemistry, Research

Antimicrobial resistance (AMR) represents a serious and growing threat to human health worldwide. It already kills 700 000 people globally every year, and that number could increase to 10 million by 2050. To combat AMR EU launched a new programme ND4BB, which features an unprecedented partnership between industry and academia, and it is supported by public and private funding. To boost early stage of antibiotic discovery (which is the most difficult stage), a new platform ENABLE was created with ND4BB program.
As a member of ENABLE consortium, we are involved in the development and optimization of molecules with the potential to become future antibacterial drug candidates.

Funding

ENABLE “European Gram-Negative Antibacterial Engine” contract 115583, www.nd4bb-enable.eu

Publications

49. Synthesis and Evaluation of Novel 5-O-(4-C-Aminoalkyl-β-D-ribofuranosyl) Apramycin Derivatives for the Inhibition of Gram-Negative Pathogens Carrying the Aminoglycoside Phosphotransferase(3′)-Ia Resistance Determinant

Lubriks, D.; Haldimann, K.; Kiliç, F.; Hartmann, M.; Böttger, E. C.; Hobbie, S. N.; Suna, E.; Crich, D. Helv. Chim. Acta 2023, e202300138
DOI: 10.1002/hlca.202300138.

44. Optimized Synthesis of Indole Carboxylate Metallo-β-Lactamase Inhibitor EBL-3183

Baran, A.; Kuzmins, J.; Kuznecovs, J.; Farley, A., J., M.; Panduwawala, T.; Parkova, A.; Donets, P., A.; Brem, J.; Suna, E.; Schofield, C., J.; Shubin, K. Org. Process Res. Dev. 2023, 27, 692–706. DOI:10.1021/acs.oprd.3c00002

41. Synthesis, Antibacterial and Antiribosomal Activity of the 3C-Aminoalkyl Modification in the Ribofuranosyl Ring of Apralogs (5-O-Ribofuranosyl Apramycins)

Lubriks, D.; Haldimann, K.; Hobbie, S. N.; Vasella A.; Suna E.; Crich D.; Antibiotics 2023, 12, 25–39. DOI: 10.3390/antibiotics12010025

38. Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors

Brem, J.; Panduwawala, T.; Hansen, J. U.; Hewitt, J.; Liepins, E.; Donets, P.; Espina, L.; Farley, A. J. M.; Shubin, K; Campillos, G. G.; Kiuru, P.; Shishodia, S.; Krahn, D.; Leśniak, R. K.; Schmidt (Adrian), J.; Calvopiña, K.; Turrientes, M. C.; Kavanagh, M. E.; Lubriks, D.; Hinchliffe, P.; Langley, G. W.; Aboklaish, A. F.; Eneroth, A.; Backlund, M.; Baran, A. G.; Nielsen, E. I.; Speake, M.; Kuka, J.; Robinson, J.; Grinberga, S.; Robinson, L.; McDonough, M. A.; Rydzik, A. M.; Leissing, T. M.; Jimenez-Castellanos, J. C.; Avison, M. B; Pinto, S. S.; Pannifer, A. D.; Martjuga, M.; Widlake, E.; Priede, M.; Navratilova, I. H.; Gniadkowski, M.; Belfrage, A. K.; Brandt, P.; Yli-Kauhaluoma, j.; Bacque, E.; Page, M. G. P.; Björkling, F.; Tyrrell, J. M.; Spencer, J.; Lang, P. A.; Baranczewski, P.; Cantón, R.; McElroy, S. P.; Jones, P. S.; Baquero, F.; Suna, E.; Morrison, A.; Walsh, T. R.; Schofield, C. J. Nat. Chem 2022, 14, 15-24.

DOI: 10.1038/s41557-021-00831-x

35. Synthesis and Antibacterial Activity of Propylamycin Derivatives Functionalized at the 5′′- and Other Positions with a View to Overcoming Resistance Due to Aminoglycoside Modifying Enzymes

Lubriks, D.; Zogota, R.; Sarpe, V., A.; Matsushita, T.; Sati, G., C.; Haldimann, K.; Gysin, M.; Böttger, E., C.; Vasella, A.; Suna, E.; Hobbie, S., N.; Crich, D. ACS Infect. Dis. 2021, 7, 2413–2424.

DOI: 10.1021/acsinfecdis.1c00158

31. Structure-activity relationship studies on the inhibition of the bacterial translation of novel Odilorhabdins analogues

Loza, E.; Sarciaux, M.; Ikaunieks, M.; Katkevics, M.; Kukosha, T.; Trufilkina, N.; Ryabova, V.; Shubin, K.; Pantel, L.; Serri, M.; Huseby, D. L.; Cao, S.; Yadav, K.; Hjort, K.; Hughes, D.; Gualtieri, M.; Suna, E.; Racine, E. Bioorg. Med. Chem. 2020, 28, 115469.

DOI: 10.1016/j.bmc.2020.115469

24. Mechanistic aspects of maltotriose-conjugate translocation to the Gram-negative bacteria cytoplasm

Dumont, E.; Vergalli, J.; Pajovic, J.; Bhamidimarri, S. P.; Morante, K.; Wang, J.; Lubriks, D.; Suna, E.; Stavenger, R. A.; Winterhalter, M.; Refregiers, M.; Pages, J. M. Life Science Alliance 2019, 2, e201800242.

DOI: 10.26508/lsa.201800242