Antibacterial Prodrugs to Overcome Bacterial Resistance

Abstract

Bacterial resistance to present antibiotics is emerging at a high pace that makes the development of new treatments a must. At the same time, the development of novel antibiotics for resistant bacteria is a slow-paced process. Amid the massive need for new drug treatments to combat resistance, time and effort preserving approaches, like the prodrug approach, are most needed. Prodrugs are pharmacologically inactive entities of active drugs that undergo biotransformation before eliciting their pharmacological effects. A prodrug strategy can be used to revive drugs discarded due to a lack of appropriate pharmacokinetic and drug-like properties, or high host toxicity. A special advantage of the use of the prodrug approach in the era of bacterial resistance is targeting resistant bacteria by developing prodrugs that require bacterium-specific enzymes to release the active drug. In this article, we review the up-to-date implementation of prodrugs to develop medications that are active against drug-resistant bacteria.

Cellulosic Polymers for Enhancing Drug Bioavailability in Ocular Drug Delivery Systems

“…Secondly, by increasing the corneal permeability, through the use of prodrugs, penetration enhancers, and a colloidal system, such as nanoparticles and liposomes [84]. Prodrugs are inactive substances; they need to be transformed chemically or enzymatically [85]. The active compound has carboxyl or hydroxyl groups that are esterified to give a lipophilic substance.…”

Anthelmintics for drug repurposing: Opportunities and challenges

“…There are two major classes of prodrugs, including carrier-linked prodrugs and bioprecursors ( Jornada et al, 2016 ). Carrier-linked prodrugs are composed of a drug linked to a promoiety, which is eliminated through a chemical or enzymatic reaction, leading to the drug release ( Jubeh, Breijyeh, & Karaman, 2020 ), while bioprecursor prodrugs have no carrier and are quickly converted to an active drug through oxidation or reduction reactions ( Jornada et al, 2016 , Jubeh et al, 2020 ).…”

Macrocycle-Antibiotic Hybrids: A Path to Clinical Candidates

“…Generally, the antibiotic hybrid umbrella covers dual-acting antibiotic hybrids, divalent or multivalent antibiotics, antibiotic conjugates, chimeric antibiotics, and antibiotic hybrid prodrugs (Wang et al, 2016;Domalaon et al, 2018). The latter involves a cleavable linker between synthons, which can be metabolized only by a specific strain, a very useful strategy for the development of narrow-spectrum antibacterial agents (Domalaon et al, 2018;Jubeh et al, 2020). In the belligerence of drug resistance, molecules composed of two or more active structure motifs that are capable of acting at their respective targets have been extensively explored (Shavit et al, 2017).…”