Towards understanding the mechanism of action of antibacterial N-alkyl-3-hydroxypyridinium salts: Biological activities, molecular modeling and QSAR studies

Doležal, Rafael; Soukup, Ondřej; Maliňák, Dávid; Savedra, Ranylson Marcello Leal; Marek, Jan; Doležalová, Marie; Pasdiorová, Markéta; Salajkova, Sarka; Korábečný, Jan; Honegr, Jan; Ramalho, Teodorico C.; Kuča, Kamil

doi:10.1016/j.ejmech.2016.05.058

Cited by 43 publications

(35 citation statements)

References 61 publications

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“…In order to compare the cytotoxic effects of studied compounds in their free state, the cytotoxicity of surfactants was assessed by standard MTT assay on noncancerous Chinese hamster ovary cells (CHO‐K1) that have been used previously for the cellular toxicity evaluation of quaternary ammonium compounds . Importantly, the newly synthesized POSAB (see Figure S1‐S3 for 1 H NMR, 13 C NMR and HRMS spectra) showed considerably lower or minimal cytotoxicity when compared to CTAB or MTAB (see Table and Figure S4).…”

Section: Resultsmentioning

confidence: 99%

“…Quaternary ammonium salts (QAS) are common chemical reagents widely used in pharmacy, organic chemistry and industry especially as antibacterial, antiviral and antifungal compounds . Positively charged quaternary ammonium heads interact with negatively charged cellular membranes of both Gram‐positive and Gram‐negative bacterial cells leading to its destruction and leakage of intracellular components .…”

Section: Introductionmentioning

confidence: 99%

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Highly hydrophilic cationic gold nanorods stabilized by novel quaternary ammonium surfactant with negligible cytotoxicity

Salajkova

Šrámek

Maliňák

et al. 2019

Journal of Biophotonics

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The photothermal cancer therapy using cationic gold nanorods (GNRs) stabilized by quaternary ammonium salts (QAS) have a great potential to enhance conventional cancer treatment as it promises the effective eradication of cancer cells including cells resistant to radio‐ and chemo‐therapy and the stimulation of anti‐tumor immune response. However, as the cytotoxicity of the conventional alkanethiol‐QAS compounds limits their utility in medicine, here we developed GNRs modified by novel highly hydrophilic cationic surfactant composed of the quaternary ammonium group and ethylene glycol chain N,N,N‐trimethyl‐3,6,9,12,15‐pentaoxaheptadecyl‐17‐sulfanyl‐1‐ammonium bromide (POSAB) showing insignificant cytotoxicity in the free state. Surface modification of GNRs by POSAB allowed to prepare nanoparticles with good stability in water, high cellular uptake and localization in lysosomes that are a promising alternative to alkanethiol‐stabilized GNRs especially for biomedical applications.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Highly hydrophilic cationic gold nanorods stabilized by novel quaternary ammonium surfactant with negligible cytotoxicity

Salajkova

Šrámek

Maliňák

et al. 2019

Journal of Biophotonics

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“…Therefore, in continuation of our prior studies, we hereby aimed to screen 1‐butylimidazolium derived ILs for vermicidal activities and cytotoxicity (on normal cell line MC3T3‐L1, mouse embryonic fibroblasts) to check the combined effects of extended hydrophobic factors (as alkyl chain) with different anions. Further, quantitative‐structure‐activity‐relationship (QSAR / or SAR) and molecular docking studies were performed to render the mechanistic insight for governing factors,,, and molecular basis of ILs vermicidal activities, respectively ,,. Overall, this study develops the medicinal prospects of ILs with the combining action of cation/anion and can substantially boost further research of this field.…”

Section: Resultsmentioning

confidence: 99%

Appraisal of 1‐Butylimidazole‐Derived Ionic Liquids as Anthelmintic Agents: An Experimental and In Silico Approach

et al. 2018

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We have synthesized and characterized 1‐butyl‐3‐alkylimidazolium derived ionic liquids (ILs) functionalized with various alkyl groups (‐C2H5, ‐C4H9, ‐C6H13, ‐C8H17, and ‐C10H21) and counter anions (OH-,Br-andBF4- ). Further, these ILs were tested for the vermicidal activity and cell‐viability study against the Pheretima posthuma (Indian earthworm) and MC3T3‐L1 cells, respectively. IL‐OH with higher alkyl chains (‐C10H21) displayed promising vermicidal activity as compared to other counterparts (IL−Br and IL‐BF4). Further, quantitative‐structure‐activity‐relationships (QSAR) modelling was carried out using density functional theory (DFT) derived quantum mechanical descriptors to assess the factors responsible for the biological activities. Based on the QSAR study it was found that LUMO of the anion and polar surface area of the cation possess significant correlation (r2, 0.85; RMSE, 0.06). Also, receptor‐binding based molecular docking was carried out to study the binding patterns of the tested IL. Introduction In past few decades, ionic liquids (ILs) have generated paramount interest in several field of chemistry, i.e., catalysis, electrochemistry,, biotechnology, biomass energy and pharmaceutical applications–, and many others. This wide range of applications are due to their characteristic tunable nature of ILs which facilitate desired biochemical properties via varying their counter anions and alkyl chain length., Subsequent tailoring of biologically active cations or anions can add substantial potential to their therapeutic implication and administration as active pharmaceutical ingredients (APIs)., Efforts are made to probe the effects of various anions, alkyl chains and charge on the quaternary nitrogen atom. It has been articulated that medicinal aspect of ILs is greatly impeded by their toxicity; however, attempts are in the progress to afford a balance between toxicity and biochemical/ biopharmaceutical properties. In particular, the maxim “poison is in the dose”, encouraged to develop ILs as useful therapeutics. Earlier, we have screened the imidazolium derived ILs for their vermicidal activity with varying alkyl chains (R= ‐C2H5, ‐C4H9, ‐C6H13, ‐C8H17) and Br−/OH− as counter anions.

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“…The systems were equilibrated in the NVT ensemble for 50,000 steps, followed by equilibration in the NPT ensemble for an additional 50,000 steps. Finally, 50 ns molecular dynamics simulations were performed at 300 K with a 2.0 fs time step, and coordinates were saved every picosecond for analysis [ 38 , 39 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of Novel Src Inhibitors: Pharmacophore-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations

Zhang

et al. 2020

Molecules

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Src plays a crucial role in many signaling pathways and contributes to a variety of cancers. Therefore, Src has long been considered an attractive drug target in oncology. However, the development of Src inhibitors with selectivity and novelty has been challenging. In the present study, pharmacophore-based virtual screening and molecular docking were carried out to identify potential Src inhibitors. A total of 891 molecules were obtained after pharmacophore-based virtual screening, and 10 molecules with high docking scores and strong interactions were selected as potential active molecules for further study. Absorption, distribution, metabolism, elimination and toxicity (ADMET) property evaluation was used to ascertain the drug-like properties of the obtained molecules. The proposed inhibitor–protein complexes were further subjected to molecular dynamics (MD) simulations involving root-mean-square deviation and root-mean-square fluctuation to explore the binding mode stability inside active pockets. Finally, two molecules (ZINC3214460 and ZINC1380384) were obtained as potential lead compounds against Src kinase. All these analyses provide a reference for the further development of novel Src inhibitors.

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Towards understanding the mechanism of action of antibacterial N-alkyl-3-hydroxypyridinium salts: Biological activities, molecular modeling and QSAR studies

Cited by 43 publications

References 61 publications

Highly hydrophilic cationic gold nanorods stabilized by novel quaternary ammonium surfactant with negligible cytotoxicity

Highly hydrophilic cationic gold nanorods stabilized by novel quaternary ammonium surfactant with negligible cytotoxicity

Appraisal of 1‐Butylimidazole‐Derived Ionic Liquids as Anthelmintic Agents: An Experimental and In Silico Approach

Identification of Novel Src Inhibitors: Pharmacophore-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations

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