Infectious diseases are among the major health issues of the 21st century. The substantial use of antibiotics over the years has contributed to the dissemination of multidrug resistant bacteria. According to a recent report by the World Health Organization, antibacterial (ATB) drug resistance has been one of the biggest challenges, as well as the development of effective long-term ATBs. Since pathogens quickly adapt and evolve through several strategies, regular ATBs usually may result in temporary or noneffective treatments. Therefore, the demand for new therapies methods, such as nano-drug delivery systems (NDDS), has aroused huge interest due to its potentialities to improve the drug bioavailability and targeting efficiency, including liposomes, nanoemulsions, solid lipid nanoparticles, polymeric nanoparticles, metal nanoparticles, and others. Given the relevance of this subject, this review aims to summarize the progress of recent research in antibacterial therapeutic drugs supported by nanobiotechnological tools.

Background: PRMT5 is a major enzyme responsible for the post-translational symmetric demethylation of protein arginine residues, which has been validated as an effective therapeutic target for cancer. Thus, many nucleoside-based PRMT5 inhibitors have been reported in the past year. Objective: To discover a novel series of non-nucleoside PRMT5 inhibitors through a molecular docking-based virtual screening approach. Methods: Our in-house compound library was virtually screened using the Glide program, identifying a new PRMT5 inhibitor 1. Based on the structural similarity of hit 1, a series of structure-oriented derivatives, including 3a-3e, 7a-7g, and 12a-12f, were synthesized and selected for the inhibitory activity evaluation against PRMT5, as well as cytotoxicity against MV4-11 cell. Results: The analogs 7a-7e with benzimidazole core exhibited potent PRMT5 inhibitory activities, with 7e displaying the most potent activity with an IC50 of 6.81 ± 0.12 μM. In the anti-proliferative assay, compound 7e showed a strong inhibitory effect on MV4-11 cell growth. Finally, the binding mode of 7e with PRMT5 was predicted to provide insights for further structural optimization. Conclusion: The newly discovered PRMT5 inhibitors have potential antitumor activity against MV4-11 cells. This work highlighted this series of 3-(1H-benzo[d]imidazol-2-yl)aniline derivatives as novel anti-cancer lead compounds targeting PRMT5, which were worthy of further investigation.