Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Evaluation of Synergistic Effect of Heteroaryl-Ethylene Molecules in Combination with Antibiotics: A Preliminary Study on Control Strains

Carmelo Bonomo
,
Paolo Giuseppe Bonacci
ORCID logo ,
Dalida Angela Bivona
,
Alessia Mirabile
,
Dafne Bongiorno
* ,
Emanuele Nicitra
ORCID logo ,
Andrea Marino
ORCID logo ,
Carmela Bonaccorso
* ,
Giuseppe Consiglio
,
Cosimo Gianluca Fortuna
,
Stefania Stefani
ORCID logo ,
Nicolò Musso
ORCID logo
Version 1 : Received: 21 July 2023 / Approved: 21 July 2023 / Online: 24 July 2023 (09:26:48 CEST)

A peer-reviewed article of this Preprint also exists.

Bonomo, C.; Bonacci, P.G.; Bivona, D.A.; Mirabile, A.; Bongiorno, D.; Nicitra, E.; Marino, A.; Bonaccorso, C.; Consiglio, G.; Fortuna, C.G.; Stefani, S.; Musso, N. Evaluation of the Effects of Heteroaryl Ethylene Molecules in Combination with Antibiotics: A Preliminary Study on Control Strains. Antibiotics 2023, 12, 1308. Bonomo, C.; Bonacci, P.G.; Bivona, D.A.; Mirabile, A.; Bongiorno, D.; Nicitra, E.; Marino, A.; Bonaccorso, C.; Consiglio, G.; Fortuna, C.G.; Stefani, S.; Musso, N. Evaluation of the Effects of Heteroaryl Ethylene Molecules in Combination with Antibiotics: A Preliminary Study on Control Strains. Antibiotics 2023, 12, 1308.

Abstract

: Introduction: Discovering compounds with antibacterial activity is crucial in the current fight against antibiotic-resistance. Material and Methods: We generate two QSAR model to design six new heteroaryl drug candidates; we assessed the antibacterial properties of the compounds against nine ATCC strains, the majority being part of the ESKAPE group, that include Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and also Salmonella enterica and Escherichia coli. We performed a synergic assay in which we combined PB4, a compound that we have previously tested in published studies, with GC-VI-70, one of the new compounds with the best cytotoxicity/MIC profile. We tested sub-MIC concentrations of PB4 with five antibiotics (linezolid, gentamycin, ampicillin, erythromycin, rifampin and imipenem) to examine the synergic effect on the ATCC strains. To evaluate compounds’ cytotoxicity, we performed a 24-hour and 48-hour 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on Colorectal Adenocarcinoma (CaCo-2) cells. The antibiotics were tested, alone and in combination with PB4. Results: PB4 lowered the MIC measured for GC-VI-70 and for the various antibiotics employed in clinical use, and all the compounds presented in this study have cytotoxic activity against cells. Conclusions: These compounds show promising use in combination with antibiotics to improve their effectiveness at low concentrations, to prevent unwanted cytotoxic effects.

Keywords

Antimicrobial Resistant; heteroaryl-ethylene derivatives; QSAR model; Antibiotics; Antitumour compounds; Combination Therapy

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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