Enhanced antibacterial activity of a novel protein-arginine deiminase type-4 (PADI4) inhibitor after conjugation with a biocompatible nanocarrier

Abstract

The present study reveals a simple and cost-effective method to enhance the antibacterial activity of a model antibiotic drug azithromycin which can also be used as an inhibitor of protein-arginine deiminase type-4 (PADI4). At first, molecular docking has been used for obtaining binding modes and binding affinities of this drug to prove its role as an effective inhibitor for protein-arginine deiminase type-4 (PADI4). In the next step, a biocompatible nanocarrier has been synthesized for successful targeting of the drug azithromycin to enhance its efficiency to a greater extent. For the formation of the nanocarrier, Cu–Ag–Fe2O3 nanocomposite has been synthesized by mechanical alloying the Cu, Ag and Fe2O3 powder for 3 h. After the successful formation of the nanocomposite, 10 wt% of the drug has been conjugated with the nanocomposite by further milling for 1 h under the same experimental condition. The nanocomposite (NC) and drug conjugated nanocomposite (NC-DC) samples are well-characterized by the Rietveld refinement of the XRD pattern of the NC-DC sample, analyzing FTIR, EDS spectra, and FESEM images. It has been observed that both the samples are non-toxic to human normal lung fibroblast WI38 cells. The antibacterial activity of the drug conjugated nanocomposite sample has been enhanced significantly compared to the pure drug azithromycin. These investigations have been made by agar cup assay and minimum inhibitory concentrations (MIC) studies. As a minimal amount of drug is required for the conjugation, side effects and the cost of an expensive drug can be minimized to a great extent following the proposed synthesis route. The enhancement of the antibacterial activity of azithromycin conjugated nanocomposite gives a possibility that drug conjugated nanocomposite may have enhanced activity in the inhibition of PADI4. It may cure the harmful effects of COVID-19 or inhibit the growth of tumour cells more efficiently by improving the cell membrane penetration power of the drug due to its conjugation with the nanocomposite.