An Updated Review on the Synthesis and Antibacterial Activity of Molecular Hybrids and Conjugates Bearing Imidazole Moiety

Abstract

The rapid growth of serious infections caused by antibiotic resistant bacteria, especially the nosocomial ESKAPE pathogens, has been acknowledged by Governments and scientists and is one of the world’s major health problems. Various strategies have been and are currently investigated and developed to reduce and/or delay the bacterial resistance. One of these strategies regards the design and development of antimicrobial hybrids and conjugates. This unprecedented critical review, in which our continuing interest in the synthesis and evaluation of the bioactivity of imidazole derivatives is testified, aims to summarise and comment on the results obtained from the end of the 1900s until February 2020 in studies conducted by numerous international research groups on the synthesis and evaluation of the antibacterial properties of imidazole-based molecular hybrids and conjugates in which the pharmacophoric constituents of these compounds are directly covalently linked or connected through a linker or spacer. In this review, significant attention was paid to summarise the strategies used to overcome the antibiotic resistance of pathogens whose infections are difficult to treat with conventional antibiotics. However, it does not include literature data on the synthesis and evaluation of the bioactivity of hybrids and conjugates in which an imidazole moiety is fused with a carbo- or heterocyclic subunit.

Pathogenic Characteristics and Risk Factors for ESKAPE Pathogens Infection in Burn Patients

“… 11 Antimicrobial-resistant ESKAPE pathogens have been considered as the global major healthcare problem by many scientists and governments. 12 Moreover, the emergence of multi-drug resistant ESKAPE (MDR-ESKAPE) makes the treatment of burn patients more difficult, resulting in poor prognosis and high mortality. Therefore, appropriate control measures are highly needed to prevent bacterial infections in burn patients.…”

Imidazole and Imidazolium Antibacterial Drugs Derived from Amino Acids

“…Aromatic heterocycles, particularly the imidazole ring, have been used in the last decades as structural skeletons to obtain different types of bioactive compounds with antibacterial, antifungal, anticancer, antiviral, antidiabetic, and other properties [ 1 , 2 , 3 , 4 ]. The search for new potent drug molecules derived from imidazole continues to be an intense area of investigation in medicinal chemistry [ 5 , 6 , 7 ]. Moreover, pharmaceutical research, manufacture, and regulation are enhancing the development of solid active ingredients, delivered as powders or tablets; however, many solid drugs which perform well in in vitro evaluation remain too insoluble for the body to absorb [ 8 , 9 ].…”

Macrocycle-Antibiotic Hybrids: A Path to Clinical Candidates

“…The underlying factor for treatment failure is resistance by biofilms that form a protective shield to reduce the penetration of metronidazole (Ma et al, 2020). Leaving the essential nitroimidazole moiety intact, conjugates of metronidazole (Patel et al, 2021), via N 1 -alkyl or 2-methyl linker or both, with different structural nuclei such as thiomorpholine-1,1-dioxide, have resulted in hybrids with superior activity against metronidazole sensitive as well as resistant H. pylori strains (Rossi and Ciofalo, 2020). Accordingly, the pharmacophore of metronidazole, a 5-nitroimidazole motif, was conjugated with rifamycin, an established agent against biofilm-forming pathogens.…”