Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 9 January 2023 / Approved: 11 January 2023 / Online: 11 January 2023 (11:51:38 CET)

A peer-reviewed article of this Preprint also exists.

Palacios-Can, F.J.; Silva-Sánchez, J.; León-Rivera, I.; Tlahuext, H.; Pastor, N.; Razo-Hernández, R.S. Identification of a Family of Glycoside Derivatives Biologically Active against Acinetobacter baumannii and Other MDR Bacteria Using a QSPR Model. Pharmaceuticals 2023, 16, 250. Palacios-Can, F.J.; Silva-Sánchez, J.; León-Rivera, I.; Tlahuext, H.; Pastor, N.; Razo-Hernández, R.S. Identification of a Family of Glycoside Derivatives Biologically Active against Acinetobacter baumannii and Other MDR Bacteria Using a QSPR Model. Pharmaceuticals 2023, 16, 250.

Abstract

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.

Keywords

QSPR model; antibacterials; Acinetobacter baumannii; natural products; virtual screening

Subject

Biology and Life Sciences, Immunology and Microbiology

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