Investigations into the structure–activity relationship in gemini QACs based on biphenyl and oxydiphenyl linker

Vereshchagin, Anatoly N.; Frolov, Nikita A.; Konyuhova, Valeria Yu.; Kapelistaya, Ekaterina A.; Hansford, Karl A.; Egorov, Mikhail P.

doi:10.1039/d0ra08900a

Cited by 16 publications

(8 citation statements)

References 45 publications

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“…On the other hand, compounds that exhibit, for example, many positively charged nitrogen atoms like those reported by Vereshchagin and co-workers [ 57 ] or molecules with unusual functional groups like those reported by Siricilla [ 58 ] are not well predicted by our model in accordance with the results of the outliers analyzed previously. This fact can be explained by the limited number of similar molecules (charge and scaffold related) used in the generation of the QSPR model.…”

Section: Resultssupporting

confidence: 76%

Identification of a Family of Glycoside Derivatives Biologically Active against Acinetobacter baumannii and Other MDR Bacteria Using a QSPR Model

et al. 2023

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As the rate of discovery of new antibacterial compounds for multidrug-resistant bacteria is declining, there is an urge for the search for molecules that could revert this tendency. Acinetobacter baumannii has emerged as a highly virulent Gram-negative bacterium that has acquired multiple resistance mechanisms against antibiotics and is considered of critical priority. In this work, we developed a quantitative structure-property relationship (QSPR) model with 592 compounds for the identification of structural parameters related to their property as antibacterial agents against A. baumannii. QSPR mathematical validation (R2 = 70.27, RN = −0.008, a(R2) = 0.014, and δK = 0.021) and its prediction ability (Q2LMO = 67.89, Q2EXT = 67.75, a(Q2) = −0.068, δQ = 0.0, rm2¯ = 0.229, and Δrm2 = 0.522) were obtained with different statistical parameters; additional validation was done using three sets of external molecules (R2 = 72.89, 71.64 and 71.56). We used the QSPR model to perform a virtual screening on the BIOFACQUIM natural product database. From this screening, our model showed that molecules 32 to 35 and 54 to 68, isolated from different extracts of plants of the Ipomoea sp., are potential antibacterials against A. baumannii. Furthermore, biological assays showed that molecules 56 and 60 to 64 have a wide antibacterial activity against clinically isolated strains of A. baumannii, as well as other multidrug-resistant bacteria, including Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. Finally, we propose 60 as a potential lead compound due to its broad-spectrum activity and its structural simplicity. Therefore, our QSPR model can be used as a tool for the investigation and search for new antibacterial compounds against A. baumannii.

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Section: Resultssupporting

confidence: 76%

Identification of a Family of Glycoside Derivatives Biologically Active against Acinetobacter baumannii and Other MDR Bacteria Using a QSPR Model

et al. 2023

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“…For the three sets of data there is a good correlation between experimental and predicted pMIC values, with 𝑅 2 values of 72.89, 71.64 and 71.56 respectively. On the other hand, compounds that exhibit, for example, positively charged nitrogen atoms like those reported by Vereshchagin and co-workers [57], are not well predicted by our model in accordance with the results of the outliers analyzed previously.…”

Section: Qspr Model Validationsupporting

confidence: 88%

Identification of a Family of Glycoside Derivatives Biologically Active Against <em>Acinetobacter baumannii</em> and Other MDR Bacteria Using a QSPR Model

Palacios-Can¹,

Silva-Sánchez²,

León‐Rivera³

et al. 2023

Preprint

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As the rate of discovery of new antibacterial compounds towards multidrug resistant bacteria is declining, there is an urge for the search of molecules that could revert this tendency. Acinetobacter baumannii has emerged as a highly virulent Gram-negative bacterium that has acquired multiple mechanisms against antibiotics and is considered of critical priority. In this work we developed a quantitative structure-property relationship (QSPR) model with 592 compounds for the identification of structural parameters related to their property as antibacterial agents against A. baumannii. QSPR mathematical validation (R2 = 70.27, RN = -0.008, aR2 = 0.014 and δK = 0.021) and its prediction ability (Q2LMO= 67.89, Q2EXT = 67.75, a(Q2)= -0.068, δQ = 0.0, rm2 = 0.229, and ∆rm2 = 0.522) were obtained with different statistical parameters; additional validation jobs were done using three sets of external molecules (R2 = 72.89, 71.64 and 71.56). We used the QSPR model to perform a virtual screening on the BIOFACQUIM natural product database. From this screening our model showed that molecules 32 to 35 and 54 to 68, isolated from different extracts of plants of the Ipomoea sp., are potential antibacterial against A. baumannii. Furthermore, biological assays showed that molecules 56 and 60 to 64 have a wide antibacterial activity against clinical isolated strains of A. baumannii, as well as other multidrug resistant bacteria including Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. Finally, we propose 60 as a potential lead compound due to its broad-spectrum activity and its structural simplicity. Therefore, our QSPR model can be used as a tool for the investigation and search of new antibacterial compounds against A. baumannii.

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“…Thus, bis-QACs with 1,4-dioxophenyl as spacer 79 were significantly more active than commercial QACs (BAC 1, CHG 7) [119][120][121]. Vereshchagin's group studied the dependence of the activity of biocides on the size of the aromatic spacer of salts, as well as the location of the spacer relative to the charged pyridinium nitrogen 79-83 [122][123][124][125][126]. It was discovered that the QAC activity increased upon increasing the length of the aromatic spacer.…”

Section: Double-charged Qacs (Bis-qacs)mentioning

confidence: 99%

“…The influence of the position of substitution in pyridine turned out to be ambiguous. In the case of biphenyl 80, the meta-salts turned out to be slightly more active than the para-derivatives, while the opposite was observed for the more mobile biphenyl ether 81 [123,126]. The ortho-salts showed strikingly lower activity.…”

Section: Double-charged Qacs (Bis-qacs)mentioning

confidence: 99%

Quaternary Ammonium Compounds (QACs) and Ionic Liquids (ILs) as Biocides: From Simple Antiseptics to Tunable Antimicrobials

Vereshchagin

Frolov

Egorova

et al. 2021

IJMS

Self Cite

169

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Quaternary ammonium compounds (QACs) belong to a well-known class of cationic biocides with a broad spectrum of antimicrobial activity. They are used as essential components in surfactants, personal hygiene products, cosmetics, softeners, dyes, biological dyes, antiseptics, and disinfectants. Simple but varied in their structure, QACs are divided into several subclasses: Mono-, bis-, multi-, and poly-derivatives. Since the beginning of the 20th century, a significant amount of work has been dedicated to the advancement of this class of biocides. Thus, more than 700 articles on QACs were published only in 2020, according to the modern literature. The structural variability and diverse biological activity of ionic liquids (ILs) make them highly prospective for developing new types of biocides. QACs and ILs bear a common key element in the molecular structure–quaternary positively charged nitrogen atoms within a cyclic or acyclic structural framework. The state-of-the-art research level and paramount demand in modern society recall the rapid development of a new generation of tunable antimicrobials. This review focuses on the main QACs exhibiting antimicrobial and antifungal properties, commercial products based on QACs, and the latest discoveries in QACs and ILs connected with biocide development.

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Investigations into the structure–activity relationship in gemini QACs based on biphenyl and oxydiphenyl linker

Abstract: The synthesis and biological evaluations of new gemini QACs possessing high antibacterial and antifungal activity were performed.

Cited by 16 publications

References 45 publications

Identification of a Family of Glycoside Derivatives Biologically Active against Acinetobacter baumannii and Other MDR Bacteria Using a QSPR Model

Identification of a Family of Glycoside Derivatives Biologically Active against Acinetobacter baumannii and Other MDR Bacteria Using a QSPR Model

Identification of a Family of Glycoside Derivatives Biologically Active Against <em>Acinetobacter baumannii</em> and Other MDR Bacteria Using a QSPR Model

Quaternary Ammonium Compounds (QACs) and Ionic Liquids (ILs) as Biocides: From Simple Antiseptics to Tunable Antimicrobials

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