Syed Mohd Danish Rizvi

The present study applied a nano-synergistic approach to enhance besifloxacin’s potency via nano-formulating besifloxacin on gold nanoparticles (Besi-AuNPs) and adding quercetin as a natural synergistic compound. In fact, a one-pot AuNP synthesis approach was applied for the generation of Besi-AuNPs, where besifloxacin itself acted as a reducing and capping agent. Characterization of Besi-AuNPs was performed by spectrophotometry, DLS, FTIR, and electron microscopy techniques. Moreover, antibacterial assessment of pure besifloxacin, Besi-AuNPs, and their combinations with quercetin were performed on Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. UV-spectra showed a peak of AuNPs at 526 nm, and the electron microscopy-based size was estimated to be 15 ± 3 nm. The effective MIC50 concentrations of besifloxacin after loading on AuNPs were reduced by approximately 50% against the tested bacterial strains. Interestingly, adding quercetin to Besi-AuNPs further enhanced their antibacterial potency, and isobologram analysis showed synergistic potential (combination index below 1) for different quercetin and Besi-AuNP combinations. However, Besi-AuNPs and quercetin combinations were most effective against Gram-positive S. aureus in comparison to Gram-negative P. aeruginosa and E. coli. Their potent activity against S. aureus has its own clinical significance, as it is one the main causative agents of ocular infection, and besifloxacin is primarily used for treating infectious eye diseases. Thus, the outcomes of the present study could be explored further to provide better medication for eye infections caused by resistant pathogens.

Breast cancer is the most prevalent type of malignancy among females as per the report of the World Health Organization. There are several established chemotherapeutic regimes for the clinical management of different solid cancers; however, the after-effects of these therapeutics serve as a significant limiting factor. The natural triterpenoid compound, gedunin is one of the principal phytoconstituent found in Azadirachta indica. In this study, we have investigated the anticancer potential of gedunin against human breast cancer MDA-MB-231 and MCF-7 cells. Based on computational studies, gedunin exhibited significantly higher binding affinity of −7.1 and −6.2 Kcal/mol towards Janus kinase (JAK) and STAT proteins, respectively. Further, the anticancer potential of gedunin against human breast cancer was studied using hormone-independent and -dependent MCF-7 and MDA-MB-231 cell lines, respectively. The results indicated that gedunin inhibited the growth and multiplication of both MCF-7 and MDA-MB-231 cells. The nuclear fragmentation and ROS were qualitatively enhanced in the treated MCF-7 and MDA-MB-231 cells in comparison to untreated cells. The caspase-3 level was significantly enhanced with a concomitant decline in JAK1 and STAT3 mRNA expression. Based on these results, gedunin might be considered as a potential therapeutic lead against hormone-dependent and -independent breast cancer MCF-7 and MDA-MB-231 cells, respectively. However, further detailed mechanistic studies are warranted to conclusively establish the anti-breast cancer effects.