Speaker
Description
Laura Pauniņa1, Cristina Durante Cruz2, Marina Madre1, Tania Szal3, Päivi Tammela2, Aigars Jirgensons1, Björn Windshügel3, Jānis Veliks1
1 Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006, Riga, Latvia
2 Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Finland P.O. Box 56 (Viikinkaari 5E), FI-00014, Helsinki, Finland
3 Discovery Research ScreeningPort, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Schnackenburgallee 114, 22525 Hamburg, Germany
e-mail: laura.paunina@osi.lv
Bacterial resistance to the existing classes of antibiotics is one of the most important challenges for the future healthcare system and bacterial cells efflux pumps play an important role for this internal drug resistance. To reduce the ability of the efflux pumps binding to medication substrates, the molecules called efflux pump inhibitors are used to rejuvenate the antibiotics activity by binding to the efflux pump protein [1].
In the framework of the project, it was hypothesized that AcrAB-TolC efflux pump outer membrane protein TolC in Gram-negative E.coli bacteria cells could represent an attractive drug target. Therefore, structure analogs of known clinical candidate compound have been synthesized and identified their structure-activity relationships (SAR) to TolC efflux pump [2].
Acknowledgements
This project was supported under the framework of the JPIAMR – Joint Programming Initiative on Antimicrobial Resistance. B.W. was supported the German Federal Ministry for Education and Research (01KI1827A). A.J. was supported by the state education development agency (1.1.1.5/ERANET/19/03), C.D.C and P.T. were supported by the Academy of Finland (Grant no. 326261).
References:
[1] AlMatar. M., Albarri. O., Makky. E. A., Köksa. F. Pharmacol Rep., 2021, 73, 1-16.
[2] Ott. G. R., Cheng. M., Learn. K. S., Wagner. J., Gingrich. D. E., Lisko. J. G., Dorsey. B. D. Journal of Medicinal Chemistry, 2016, 59(16), 7478-7496.
