Discovery and Development of 8-Substituted Cycloberberine Derivatives As Novel Antibacterial Agents Against MRSA

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2018 May 26

PMID 29795764

Citations 3

Authors

Tianyun Fan

Xinxin Hu

Sheng Tang

Xiaojia Liu

Yanxiang Wang

Hongbin Deng

Xuefu You

Jiandong Jiang

Yinghong Li

Danqing Song

Affiliations

Soon will be listed here.

Abstract

8-Acetoxycycloberberine () with a unique skeleton was first identified to display a potent activity profile against Gram-positive bacteria, especially methicillin-resistant (MRSA) with minimum inhibitory concentration (MIC) values of 1-8 μg/mL, suggesting a possible novel mechanism of action against bacteria. Taking as the lead, 23 new 8-substituted cycloberberine (CBBR) derivatives including ether, amine, and amide were synthesized and evaluated for their antibacterial effect. The structure-activity relationship revealed that the introduction of a suitable substituent at the 8-position could greatly enhance the potency against MRSA. Among them, compounds and demonstrated equally effective anti-MRSA potency as lead , with an advantage of having a more stable pharmacokinetics feature. A preliminary mechanism study indicated that compound acted upon bacteria partly through catalyzing the cleavage of bacterial DNA. Therefore, we consider that 8-substituted CBBR derivatives constitute a promising class of antibacterial agents in the treatment of MRSA infections.

Citing Articles

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References

Li Y, Zhao W, Wang Y, Zhang C, Jiang J, Bi C . Discovery, synthesis and biological evaluation of cycloprotoberberine derivatives as potential antitumor agents. Eur J Med Chem. 2013; 68:463-72. DOI: 10.1016/j.ejmech.2013.07.026. View

Richter M, Drown B, Riley A, Garcia A, Shirai T, Svec R . Predictive compound accumulation rules yield a broad-spectrum antibiotic. Nature. 2017; 545(7654):299-304. PMC: 5737020. DOI: 10.1038/nature22308. View

Ferron G, Jusko W . Species differences in sirolimus stability in humans, rabbits, and rats. Drug Metab Dispos. 1998; 26(1):83-4. View

Chu M, Zhang M, Liu Y, Kang J, Chu Z, Yin K . Role of Berberine in the Treatment of Methicillin-Resistant Staphylococcus aureus Infections. Sci Rep. 2016; 6:24748. PMC: 4840435. DOI: 10.1038/srep24748. View

Liu C, Bayer A, Cosgrove S, Daum R, Fridkin S, Gorwitz R . Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011; 52(3):285-92. DOI: 10.1093/cid/cir034. View

Sharma M, Riederer K, Chase P, Khatib R . High rate of decreasing daptomycin susceptibility during the treatment of persistent Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis. 2008; 27(6):433-7. DOI: 10.1007/s10096-007-0455-5. View

Rybak M, Lomaestro B, Rotschafer J, Moellering Jr R, Craig W, Billeter M . Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2008; 66(1):82-98. DOI: 10.2146/ajhp080434. View

Wang Y, Pang W, Zeng Q, Deng Z, Fan T, Jiang J . Synthesis and biological evaluation of new berberine derivatives as cancer immunotherapy agents through targeting IDO1. Eur J Med Chem. 2017; 143:1858-1868. DOI: 10.1016/j.ejmech.2017.10.078. View

Sashidhara K, Rao K, Kushwaha P, Modukuri R, Singh P, Soni I . Novel Chalcone-Thiazole Hybrids as Potent Inhibitors of Drug Resistant Staphylococcus aureus. ACS Med Chem Lett. 2015; 6(7):809-13. PMC: 4499817. DOI: 10.1021/acsmedchemlett.5b00169. View

10.

Sun N, Du R, Zheng Y, Huang B, Guo Q, Zhang R . Antibacterial activity of N-methylbenzofuro[3,2-b]quinoline and N-methylbenzoindolo[3,2-b]-quinoline derivatives and study of their mode of action. Eur J Med Chem. 2017; 135:1-11. DOI: 10.1016/j.ejmech.2017.04.018. View

11.

Mohammad H, Mayhoub A, Ghafoor A, Soofi M, Alajlouni R, Cushman M . Discovery and characterization of potent thiazoles versus methicillin- and vancomycin-resistant Staphylococcus aureus. J Med Chem. 2014; 57(4):1609-15. PMC: 4353699. DOI: 10.1021/jm401905m. View

12.

Jeyakkumar P, Zhang L, Avula S, Zhou C . Design, synthesis and biological evaluation of berberine-benzimidazole hybrids as new type of potentially DNA-targeting antimicrobial agents. Eur J Med Chem. 2016; 122:205-215. DOI: 10.1016/j.ejmech.2016.06.031. View

13.

Magiera S, Kusa J . Evaluation of a rapid method for the therapeutic drug monitoring of aliskiren, enalapril and its active metabolite in plasma and urine by UHPLC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2015; 980:79-87. DOI: 10.1016/j.jchromb.2014.12.025. View

14.

Mohammad H, Reddy P, Monteleone D, Mayhoub A, Cushman M, Seleem M . Synthesis and antibacterial evaluation of a novel series of synthetic phenylthiazole compounds against methicillin-resistant Staphylococcus aureus (MRSA). Eur J Med Chem. 2015; 94:306-16. PMC: 4716659. DOI: 10.1016/j.ejmech.2015.03.015. View

15.

Han J, Edelstein P, Lautenbach E . Reduced vancomycin susceptibility and staphylococcal cassette chromosome mec (SCCmec) type distribution in methicillin-resistant Staphylococcus aureus bacteraemia. J Antimicrob Chemother. 2012; 67(10):2346-9. PMC: 3444231. DOI: 10.1093/jac/dks255. View

16.

Brown E, Wright G . Antibacterial drug discovery in the resistance era. Nature. 2016; 529(7586):336-43. DOI: 10.1038/nature17042. View

17.

Kullar R, Casapao A, Davis S, Levine D, Zhao J, Crank C . A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis. J Antimicrob Chemother. 2013; 68(12):2921-6. PMC: 3820108. DOI: 10.1093/jac/dkt294. View

18.

Liu J, Obando D, Liao V, Lifa T, Codd R . The many faces of the adamantyl group in drug design. Eur J Med Chem. 2011; 46(6):1949-63. DOI: 10.1016/j.ejmech.2011.01.047. View

19.

Kelley C, Zhang Y, Parhi A, Kaul M, Pilch D, LaVoie E . 3-Phenyl substituted 6,7-dimethoxyisoquinoline derivatives as FtsZ-targeting antibacterial agents. Bioorg Med Chem. 2012; 20(24):7012-29. PMC: 3947851. DOI: 10.1016/j.bmc.2012.10.009. View

20.

Bi C, Zhang C, Li Y, Zhao W, Shao R, Mei L . [Synthesis and structure-activity relationship of cycloberberine as anti-cancer agent]. Yao Xue Xue Bao. 2014; 48(12):1800-6. View