Antiretroviral Therapy (ART) is an effective treatment for human immunodeficiency virus (HIV) which has transformed the highly lethal disease, acquired immunodeficiency syndrome (AIDS), into a chronic and manageable condition. However, better methods need to be developed for enhancing patient access and adherence to therapy and for improving treatment in the long term to reduce adverse effects. From the perspective of drug discovery, one promising strategy is the development of anti-HIV prodrugs. This approach aims to enhance the efficacy and safety of treatment, promoting the development of more appropriate and convenient systems for patients. In this review, we discussed the use of the prodrug approach for HIV antiviral agents and emphasized nucleoside reverse transcriptase inhibitors. We comprehensively described various strategies that are used to enhance factors such as water solubility, bioavailability, pharmacokinetic parameters, permeability across biological membranes, chemical stability, drug delivery to specific sites/organs, and tolerability. These strategies might help researchers conduct better studies in this field. We also reported successful examples from the primary therapeutic classes while discussing the advantages and limitations. In this review, we highlighted the key trends in the application of the prodrug approach for treating HIV/AIDS.

The emergence of multidrug‐resistant strains of M. tuberculosis has raised concerns due to the greater difficulties in patient treatment and higher mortality rates. Herein, we revisited the 2‐nitro‐6,7‐dihydro‐5H‐imidazo[2,1‐b][1,3]oxazine scaffold and identified potent new carbamate derivatives having MIC₉₀ values of 0.18–1.63 μM against Mtb H37Rv. Compounds 47–49, 51–53, and 55 exhibited remarkable activity against a panel of clinical isolates, displaying MIC₉₀ values below 0.5 μM. In Mtb‐infected macrophages, several compounds demonstrated a 1‐log greater reduction in mycobacterial burden than rifampicin and pretomanid. The compounds tested did not exhibit significant cytotoxicity against three cell lines or any toxicity to Galleria mellonella. Furthermore, the imidazo[2,1‐b][1,3]oxazine derivatives did not show substantial activity against other bacteria or fungi. Finally, molecular docking studies revealed that the new compounds could interact with the deazaflavin‐dependent nitroreductase (Ddn) in a similar manner to pretomanid. Collectively, our findings highlight the chemical universe of imidazo[2,1‐b][1,3]oxazines and their promising potential against MDR‐TB.

The effective treatment of human immunodeficiency virus (HIV), also known as acquired immunodeficiency syndrome (AIDS), has transformed a highly lethal disease into a chronic and manageable condition. However, better methods need to be developed for eliminating the virus from reservoirs, enhancing patient access and adherence to therapy, and improving treatment in the long term to reduce adverse effects. From the perspective of drug discovery, one promising strategy is the development of anti-HIV prodrugs. This approach aims to enhance the efficacy and safety of treatment, promoting the development of more appropriate and convenient systems for patients. In this review, we discussed the use of the prodrug approach for HIV antiviral agents and emphasized nucleoside reverse transcriptase inhibitors. We comprehensively described various strategies that are used to enhance factors such as water solubility, bioavailability, pharmacokinetic parameters, permeability across biological membranes, chemical stability, drug delivery to specific sites/organs, and tolerability. These strategies might help researchers conduct better studies in this field. We also reported successful examples from the primary therapeutic classes while discussing the advantages and limitations. In this review, we highlighted the key trends in the application of the prodrug approach for treating HIV/AIDS..

Infectious diseases remain a major global health challenge, driven by antimicrobial resistance, pathogen persistence, and the limited integration of mechanistically innovative therapeutic approaches. Emerging evidence indicates that epigenetic regulation is fundamental to host–pathogen interactions, influencing transcriptional programmes associated with virulence, immune evasion, stress adaptation, and phenotypic plasticity. In organisms such as bacteria, parasites, and intracellular pathogens, including Mycobacterium tuberculosis and Plasmodium falciparum, chromatin-associated regulators and DNA-modifying enzymes have been identified as dosage-sensitive determinants of infection outcomes. Traditional strategies focus primarily on occupancy-driven enzymatic inhibition. In contrast, targeted protein degradation (TPD) introduces an event-driven pharmacological paradigm in which transient ligand engagement triggers sustained depletion of regulatory proteins. Platforms such as proteolysis-targeting chimeras (PROTACs) and BacPROTACs exemplify the ability to exploit host and pathogen proteolytic systems, thereby expanding the druggable proteome beyond conventional small-molecule targets. This review examines the relationship between epigenetic regulation and pathogen survival, highlights recent advances in degradation technologies, and discusses conceptual and translational challenges in implementing TPD in antimicrobial and antiparasitic drug discovery.

Antimicrobial resistance (AMR) is eroding the effectiveness of our current antibiotic arsenal and threatens to outpace drug discovery efforts worldwide. Against this backdrop, the development of antibiotics with novel mechanisms of action and optimized chemical scaffolds has never been more critical. Recent approvals by the U.S. Food and Drug Administration (FDA) showcase how medicinal chemistry is driving innovation to counter multidrug-resistant (MDR) pathogens. In this review article, we examined the structural frameworks, structure-activity relationships (SARs), and pharmacokinetic and pharmacodynamic profiles of these agents, and highlighted forward-looking strategies such as siderophore-mediated uptake and non-traditional bacterial targets, including topoisomerases. We also discuss how targeted chemical modifications have expanded the antibacterial spectrum, enhanced binding affinity, and strengthened resistance profiles. Together, these advances illustrate the central role of medicinal chemistry in reshaping the antibiotic pipeline and sustaining therapeutic efficacy amid the AMR crisis.