Design, synthesis and evaluation of a series of 5-methoxy-2,3-naphthalimide derivatives as AcrB inhibitors for the reversal of bacterial resistance
| Autor: | Xinjie Gu, Chaobin Jin, Steven W. Polyak, Natansh D. Modi, Shutao Ma, Rawaf Alenazy, Yinhui Qin, Jin Quan Eugene Tan, Rumana Mowla, Henrietta Venter, Yinhu Wang |
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| Přispěvatelé: | Jin, Chaobin, Alenazy, Rawaf, Wang, Yinhu, Mowla, Rumana, Qin, Yinhui, Tan, Jin Quan Eugene, Modi, Natansh Deepak, Gu, Xinjie, Polyak, Steven W, Venter, Henrietta, Ma, Shutao |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
5-Methoxy-2
3-naphthalimide medicine.drug_class Clinical Biochemistry Antibiotics Pharmaceutical Science medicine.disease_cause 01 natural sciences Biochemistry chemistry.chemical_compound Structure-Activity Relationship Antibiotic resistance synergism Drug Discovery Drug Resistance Bacterial medicine Escherichia coli Inner membrane antimicrobial resistance inhibition of efflux Molecular Biology Molecular Structure 010405 organic chemistry Escherichia coli Proteins Organic Chemistry Nile red Gene Expression Regulation Bacterial AcrB Antimicrobial 0104 chemical sciences Anti-Bacterial Agents 010404 medicinal & biomolecular chemistry Naphthalimides chemistry Molecular Medicine Efflux Multidrug Resistance-Associated Proteins Lead compound Efflux pump inhibitor |
| Popis: | A series of novel 5-methoxy-2,3-naphthalimide derivatives were designed, synthesized and evaluated for their biological activities. In particular, the ability of the compounds to synergize with antimicrobials, to inhibit Nile Red efflux, and to target AcrB was assayed. The results showed that the most of the tested compounds more sensitized the Escherichia coli BW25113 to the antibiotics than the parent compounds 7c and 15, which were able to inhibit Nile Red efflux. Significantly, compound A5 possessed the most potent antibacterial synergizing activity in combination with levofloxacin by 4 times and 16 times at the concentration of 8 and 16 µg/mL, respectively, whilst A5 could effectively abolish Nile Red efflux at 100 μM. Additionally, target effect of A5 was confirmed in the outer- or inner membrane permeabilization assays. Therefore, A5 is an excellent lead compound for further structural optimization. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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