Enhancement of antibiotic-activity through complexation with metal ions - Combined ITC, NMR, enzymatic and biological studies

Möhler, Jasper S.; Kolmar, Theresa; Synnatschke, Kevin; Hergert, Marcel; Wilson, Liam A.; Ramu, Soumya; Elliott, Alysha G.; Blaskovich, Mark A. T.; Sidjabat, Hanna E.; Paterson, David L.; Schenk, Gerhard; Cooper, Matthew A.; Ziora, Zyta M.

doi:10.1016/j.jinorgbio.2016.11.028

Cited by 54 publications

(38 citation statements)

References 37 publications

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“…The concentration dependence of the PenNa chemical shifts using DMSO-d 6 solvent: The concentration dependence of the geminal proton resonances in D 2 O has been previously reported [22]. Herein we report our study for the dimethylsulfoxide solvent.…”

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confidence: 73%

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Conjugation of Penicillin-G with Silver(I) Ions Expands Its Antimicrobial Activity against Gram Negative Bacteria

et al. 2020

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Conjugation of penicillin G (PenH) with silver(I) ions forms a new CoMeD (conjugate of metal with a drug) with formula [Ag(pen)(CH3OH)]2 (PenAg). PenAg was characterized by a plethora of physical and spectroscopic techniques, which include in the solid state m.p.; elemental analysis; X-ray fluorescence (XRF) spectroscopy; scanning electron microscopy (SEM); energy-dispersive X-ray spectroscopy (EDX); FT-IR; and in solution: attenuated total reflection spectroscopy (FT-IR-ATR), UV–Vis, 1H NMR, and atomic absorption (AA). The structure of PenAg was determined by NMR spectroscopy. Silver(I) ions coordinate to the carboxylic group of PenH, while secondary intra-molecular interactions are developed through (i) the nitrogen atom of the amide group in MeOD-d4 or (ii) the sulfur atom in the thietane ring in deuterated dimethyl sulfoxide DMSO-d6. The antibacterial activities of PenAg and the sodium salt of penicillin (PenNa) (the formulation which is clinically used) against Gram positive (Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus)) and Gram negative (Pseudomonas aeruginosa (P. aeuroginosa PAO1)) bacteria were evaluated by the means of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and inhibition zone (IZ). PenAg inhibits the growth of the Gram negative bacterial strain P. aeuroginosa with a MIC value of 23.00 ± 2.29 μM, in contrast to PenNa, which shows no such activity (>2 mM). The corresponding antimicrobial activities of PenAg against the Gram positive bacteria S. epidermidis and S. aureus are even better than those of PenNa. Moreover, PenAg exhibits no in vivo toxicity against Artemia salina at concentration up to 300 μΜ. The wide therapeutic window and the low toxicity, make PenAg a possible candidate for the development of a new antibiotic.

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confidence: 73%

“…(A) (B) Structure of PenAg by NMR spectroscopy with 500MHz LC-NMR instrumentation: An NMR study of PenNa has been previously reported [22,23]. Herein the binding mode of PenNa at PenAg is reported.…”

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confidence: 99%

Conjugation of Penicillin-G with Silver(I) Ions Expands Its Antimicrobial Activity against Gram Negative Bacteria

et al. 2020

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“…Enhancement of antibiotic activity through complexation with metal ions is well ascertained. Copper (II), zinc (II) and silver (I) metal adducts with different antibiotics were extensively studied in recent years [ 242 , 243 , 244 , 245 ]. Cu(II) and Ag(I) themselves have antimicrobial activity [ 246 ], but together with antibiotics e.g., ampicillin, penicillin G and Cefuroxime, they present synergistic effects against Gram-positive (MRSA) bacteria ( S. aureus ).…”

Section: Enhancing Amps Activity With Metal Ionsmentioning

confidence: 99%

“…Cu(II) and Ag(I) themselves have antimicrobial activity [ 246 ], but together with antibiotics e.g., ampicillin, penicillin G and Cefuroxime, they present synergistic effects against Gram-positive (MRSA) bacteria ( S. aureus ). Zn(II) is an essential cofactor for metallo-β-lacamases (enzyme resistant to β-lactan antibiotics), and together with ampicillin and penicillin G shows a high synergistic effect [ 245 ].…”

Section: Enhancing Amps Activity With Metal Ionsmentioning

confidence: 99%

The Best Peptidomimetic Strategies to Undercover Antibacterial Peptides

Lachowicz

Szczepski

Scano

et al. 2020

IJMS

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Health-care systems that develop rapidly and efficiently may increase the lifespan of humans. Nevertheless, the older population is more fragile, and is at an increased risk of disease development. A concurrently growing number of surgeries and transplantations have caused antibiotics to be used much more frequently, and for much longer periods of time, which in turn increases microbial resistance. In 1945, Fleming warned against the abuse of antibiotics in his Nobel lecture: “The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant”. After 70 years, we are witnessing the fulfilment of Fleming’s prophecy, as more than 700,000 people die each year due to drug-resistant diseases. Naturally occurring antimicrobial peptides protect all living matter against bacteria, and now different peptidomimetic strategies to engineer innovative antibiotics are being developed to defend humans against bacterial infections.

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“…A resistência aos antibióticos é uma preocupação crescente na medicina e leva à necessidade de desenvolver e desenhar novas moléculas, potenciais fármacos, que possam inibir eficazmente a replicação bacteriana. Várias soluções têm sido tentadas, entre elas a síntese de complexos metálicos de alguns antibióticos já bastante utilizados clinicamente [Möhler et al, 2017;Cuprys et al, 2018].…”

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Estudos Espectroscópicos De Fluorquinolonas E Seus Complexos De Cobre(ii): Interação Com Micelas, Lipossomas E Nanocompósitos De Ouro

INCIO¹

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A Deus, por me amparar sempre nos momentos difíceis, por me dar a força suficiente para vencer todas as dificuldades a serem apresentadas, por me mostrar o caminho nas horas incertas e por me suprir em todas minhas necessidades. Aos meus pais, Pedro Llontop Gonzales e Maria Esther Incio Puyen, pela minha vida, compreensão, esforço, apoio constante, e aos meus irmãos Elvis e Noelia pela ajuda nos momentos que eu precisei, muito agradecido a minha família. À minha orientadora, a Professora Sônia Renaux Wanderley Louro, por sua dedicação, ensinamentos e paciência infinita. Sem ela este trabalho não teria sido realizado. Ao professor Tommaso Del Rosso, do Departamento de Física da PUC-Rio, pela síntese e disponibilização dos nanocompósitos de ouro. Aos meus amigos, em especial meus colegas de laboratório, por me ajudar em todo o trajeto do meu doutorado, sempre me ajudando dentro do laboratório e mediante conhecimentos científicos. A todos os professores da Física pelos conhecimentos recebidos e pela acolhida mostrada.

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Enhancement of antibiotic-activity through complexation with metal ions - Combined ITC, NMR, enzymatic and biological studies

Abstract: Enhancement of antibiotic-activity through complexation with metal ionsCombined ITC, NMR, enzymatic and biological studies,

Cited by 54 publications

References 37 publications

Conjugation of Penicillin-G with Silver(I) Ions Expands Its Antimicrobial Activity against Gram Negative Bacteria

Conjugation of Penicillin-G with Silver(I) Ions Expands Its Antimicrobial Activity against Gram Negative Bacteria

The Best Peptidomimetic Strategies to Undercover Antibacterial Peptides

Estudos Espectroscópicos De Fluorquinolonas E Seus Complexos De Cobre(ii): Interação Com Micelas, Lipossomas E Nanocompósitos De Ouro

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