Design and Synthesis of Hybrid Compounds for Potential Treatment of Bacterial Co-Infections: In Vitro Antibacterial and In Silico Studies.

Publication date: Jun 06, 2025

Background: The need for innovative therapeutic strategies to enhance patient outcomes has increased due to the rise in bacterial co-infections associated with COVID-19. Methods: In this study, ten hybrid compounds were synthesized by combining two known pharmaceutical scaffolds to enhance antibacterial activity and overcome resistance mechanisms. The synthesized compounds were evaluated for their antibacterial activity against five Gram-negative and seven Gram-positive bacterial strains. In silico pharmacokinetic and drug-likeness properties of selected active compounds (12-16, 19, 21, and 23) were predicted using the SwissADME web tool. Results: Compounds 12-16, 19, 21, and 23 demonstrated significant antibacterial activity, with compound 16 (a ciprofloxacin-containing hybrid) exhibiting the most potent effect, showing a minimum inhibitory concentration (MIC) of 7. 8125 ug/mL against all tested bacterial strains. The in silico analysis revealed favorable pharmacokinetic profiles, drug-likeness, lipophilicity, and water solubility of most hybrid compounds. Discussion: The synthesized hybrid compounds exhibited enhanced antibacterial activity and desirable pharmacokinetic properties, particularly compound 16. These findings suggest the potential of these molecules in combating bacterial pathogens, especially those implicated in co-infections in COVID-19 infections. Conclusions: The study presents promising hybrid antibacterial agents with potential application as adjunct therapies for treating COVID-19-associated bacterial co-infections. Further investigation is needed, which may lead to effective treatments for managing secondary bacterial infections in viral disease contexts.

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Concepts Keywords
Antibiotics antibacterial
Desirable co-infection
Lipophilicity COVID-19
Swissadme hybrid compounds
Viral in silico studies
SwissADME
synthesis

Semantics

Type Source Name
disease MESH Co-Infections
disease MESH COVID-19
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK Ciprofloxacin
drug DRUGBANK Methyl isocyanate
drug DRUGBANK Water
disease MESH infections
disease MESH bacterial infections
disease MESH viral disease
drug DRUGBANK Etodolac
drug DRUGBANK Coenzyme M
disease IDO bacteria
disease MESH complications
disease MESH bloodstream infections
disease MESH critically ill
drug DRUGBANK Eugenol
drug DRUGBANK Thymol
drug DRUGBANK Fluconazole
drug DRUGBANK Zidovudine
drug DRUGBANK Artesunate
disease MESH candidiasis
disease MESH Gram negative bacterial infections
drug DRUGBANK Artemisinin
disease MESH malaria
pathway KEGG Malaria
disease MESH osteoporosis
disease MESH urinary tract infections
disease MESH endocarditis
disease IDO replication
drug DRUGBANK Activated charcoal
drug DRUGBANK Albendazole
disease IDO process
drug DRUGBANK Compound 18
drug DRUGBANK Dimethyl sulfoxide
drug DRUGBANK Ampicillin
drug DRUGBANK Streptomycin
drug DRUGBANK Nalidixic acid
drug DRUGBANK Aspartame
disease MESH pneumonia
disease MESH Klebsiella infections
pathway REACTOME Metabolism
drug DRUGBANK Isoxaflutole
disease IDO assay
drug DRUGBANK Phenol
drug DRUGBANK Nitrogen
drug DRUGBANK Silicon dioxide
drug DRUGBANK Aluminium
disease IDO reagent
drug DRUGBANK Cefaclor
drug DRUGBANK Acetamide
drug DRUGBANK Acetazolamide
drug DRUGBANK N N-dimethylformamide
disease IDO deoxyribonucleic acid
disease MESH influenza
disease IDO infection
disease MESH Opportunistic Infections
disease MESH bacteremia
disease MESH multiple myeloma
disease IDO susceptibility
drug DRUGBANK (S)-Des-Me-Ampa
disease MESH dysbiosis
disease IDO antibiotic resistance
drug DRUGBANK Curcumin
disease MESH nosocomial infection
drug DRUGBANK Ciclopirox
drug DRUGBANK Carboxyamidotriazole
drug DRUGBANK Guanosine
disease MESH tumor
disease MESH Tendinopathy
drug DRUGBANK L-Tyrosine
pathway REACTOME Autophagy
pathway KEGG Biofilm formation
disease IDO protein
drug DRUGBANK Polyethylene glycol
drug DRUGBANK Quinine

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