Antiplasmodial action of 4-nitrobenzenesulfonamide chalcones: Design, synthesis, characterisation, in vitro and in silico evaluation against blood stages of Plasmodium falciparum 3D7.

Malaria is an intracellular protozoan parasitic disease caused by Plasmodium species with significant morbidity and mortality in endemic regions. The complex lifecycle of the parasite and the emergence of drug-resistant Plasmodium falciparum have hampered the efficacy of current anti-malarial agents. To circumvent this situation, the present study attempts to demonstrate the blood-stage anti-plasmodial action of 26 hybrid compounds containing the three privileged bioactive scaffolds (sulfonamide, chalcone, and nitro group) with synergistic and multitarget action. These three parent scaffolds exhibit divergent activities, such as antibacterial, anti-malarial, anti-fungal, anti-inflammatory, and anticancer. All the synthesised compounds were characterised using various spectroscopic techniques. The in vitro blood-stage inhibitory activity of 26 hybrid compounds was evaluated against mixed-stage culture (asynchronize) of human malarial parasite P. falciparum, Pf 3D7 at different concentrations ranging from 25.0 µg/mL to 0.78 µg/mL using SYBR 1 green assay, with IC50 values determined after 48 h of treatment based on the drug-response curves. Two potent compounds (11 and 10), with 2-Br and 2,6-diCl substitutions, showed pronounced activity with IC50 values of 5.4 µg/mL and 5.6 µg/mL, whereas others displayed varied activity with IC50 values ranging from 7.0 µg/mL to 22.0 µg/mL. Both 11 and 10 showed greater susceptibility towards mature-stage trophozoites than ring-stage parasites. The hemolytic and in vitro cytotoxicity assays revealed that compounds 11 and 10 did not cause any toxic effects on host red blood cells (uninfected), human-derived Mo7e cells, and murine-derived BA/F3 cells. The in vitro observations are consistent with the in silico studies using P. falciparum-dihydrofolate reductase, where 11 and 10 showed a binding affinity of -10.4 Kcal/mol. This is the first report of the hybrid scaffold, 4-nitrobenzenesulfonamide chalcones, demonstrating its potential as an anti-plasmodial agent.

In-situ synthesis and evaluation of anti-bacterial efficacy and angiogenesis of curcumin encapsulated lipogel dermal patch for wound healing applications.

The development of synthetic hydrogels as a dermal patch offers unique advantage of providing moist environment around the wound site. The incorporation of curcumin in hydrogel plays a significant role in the healing process of chronic wounds. The present investigation aims to develop nano-formulated curcumin-fused lipogel to impart the dual advantages of sustained drug release and enhanced wound healing ability. The wound healing behaviour of the prepared lipogel has been assessed through series of techniques namely DPPH assay and bacterial inhibitory efficacy through the Kirby Bauer assay against E. coli and S. aureus. Further, the promotion of angiogenesis has been determined through an in-ovo CAM assay. The results obtained from the investigation revealed the enhanced solubility of curcumin in liposome formulation. Moreover, the encapsulation of curcumin in liposomes facilitated prolonged drug release and better antibacterial efficacy against the tested bacterial stains. The developed hydrogel also displayed good adhesion and water retention ability, which is an important prerequisite for better wound healing ability.