Small molecule interaction with lipid bilayers: A molecular dynamics study of chlorhexidine

Oosten, Brad J. Van; Marquardt, Drew; Komljenović, Ivana; Bradshaw, Jeremy P.; Sternin, Edward; Harroun, Thad A.

doi:10.1016/j.jmgm.2013.12.007

Cited by 18 publications

(22 citation statements)

References 32 publications

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“…Levofloxacin [236][237][238], Clarithromycin [236], Isoniazid N -acylated derivatives [239], Rifampicin [234,240], Mangostin [241], Trimethoprim [242], Negamycin [243] Potential antibiotic Kanamycin A [133], nTZDpa and its derivatives [244], Cholic acid derived amphiphiles [245], γ-terpineol [246], Bithionol [247] Antimicrobial compound Chlorhexidine [248][249][250], Triclosan [251], Octenidine [250] Antiparasitic Praziquantel [252] Antiviral drugs Darunavir [253], Amantadine [254][255][256], Spiro[pyrrolidine-2,2 -adamantane] [254,255], 20,30-dideoxyadenosine (Didanosine) [242], Saffron [257] Antifungal drug Itraconazole, [184,186,187,258], Nystatin [259], Amphotericin B [260] Rheumatoid arthritis Lapatinib [213] Nonsteroidal antiinflammatory drugs, inhibitor of cyclooxygenase-1 and -2…”

Section: Application and Target Drugs And Pharmaceuticsmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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We review the use of molecular dynamics (MD) simulation as a drug design tool in the context of the role that the lipid membrane can play in drug action, i.e., the interaction between candidate drug molecules and lipid membranes. In the standard “lock and key” paradigm, only the interaction between the drug and a specific active site of a specific protein is considered; the environment in which the drug acts is, from a biophysical perspective, far more complex than this. The possible mechanisms though which a drug can be designed to tinker with physiological processes are significantly broader than merely fitting to a single active site of a single protein. In this paper, we focus on the role of the lipid membrane, arguably the most important element outside the proteins themselves, as a case study. We discuss work that has been carried out, using MD simulation, concerning the transfection of drugs through membranes that act as biological barriers in the path of the drugs, the behavior of drug molecules within membranes, how their collective behavior can affect the structure and properties of the membrane and, finally, the role lipid membranes, to which the vast majority of drug target proteins are associated, can play in mediating the interaction between drug and target protein. This review paper is the second in a two-part series covering MD simulation as a tool in pharmaceutical research; both are designed as pedagogical review papers aimed at both pharmaceutical scientists interested in exploring how the tool of MD simulation can be applied to their research and computational scientists interested in exploring the possibility of a pharmaceutical context for their research.

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Section: Application and Target Drugs And Pharmaceuticsmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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“…(2014) recently reported that holding the doubly charged chlorhexidine within the membrane, in regions deeper than its minimum free energy location, may perturb the bilayer [17]. This can promote the opening of a hole in the membrane and the movement of water into the membrane [17].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…This can promote the opening of a hole in the membrane and the movement of water into the membrane [17].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Shedding light on the puzzle of drug-membrane interactions: Experimental techniques and molecular dynamics simulations

Lopes

Jakobtorweihen

Nunes

et al. 2017

Progress in Lipid Research

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“…Taurolidine undergoes several hydrolysis reactions, first a cationic taurolidine is formed [28], which may attack the negatively charged bacterial cell wall. This is a mechanism known for other antimicrobials, e.g., charged chlorhexidine binds to the bacterial cell membranes [29]. For taurolidine, non-isolable carbinolamine is the major bactericidal compound, the antimicrobial activity originates from the methylene iminium ion production [30].…”

Section: Discussionmentioning

confidence: 99%

Taurolidine Acts on Bacterial Virulence Factors and Does Not Induce Resistance in Periodontitis-Associated Bacteria—An In-Vitro Study

et al. 2020

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The aims of the present study were: (a) to determine the mechanism of action of taurolidine against bacterial species associated with periodontal disease, and (b) to evaluate the potential development of resistance against taurolidine as compared with minocycline. After visualizing the mode of action of taurolidine by transmission electron micrographs, the interaction with most important virulence factors (lipopolysaccharide (LPS), Porphyromonas gingivalis gingipains, Aggregatibacter actinomycetemcomitans leukotoxin), was analyzed. Then, 14 clinical isolates from subgingival biofilm samples were transferred on agar plates containing subinhibitory concentrations of taurolidine or minocycline up to 50 passages. Before and after each 10 passages, minimal inhibitory concentrations (MICs) were determined. Increasing MICs were screened for efflux mechanism. Taurolidine inhibited in a concentration-dependent manner the activities of LPS and of the arginine-specific gingipains; however, an effect on A. actinomycetemcomitans leukotoxin was not detected. One P. gingivalis strain developed a resistance against taurolidine, which was probably linked with efflux mechanisms. An increase of MIC values of minocycline occurred in five of the 14 included strains after exposure to subinhibitory concentrations of the antibiotic. The present results indicate that: (a) taurolidine interacts with LPS and gingipains, and (b) development of resistance seems to be a rare event when using taurolidine.

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Small molecule interaction with lipid bilayers: A molecular dynamics study of chlorhexidine

Cited by 18 publications

References 32 publications

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Shedding light on the puzzle of drug-membrane interactions: Experimental techniques and molecular dynamics simulations

Taurolidine Acts on Bacterial Virulence Factors and Does Not Induce Resistance in Periodontitis-Associated Bacteria—An In-Vitro Study

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