ABSTRACT
Background Cancer is the second most common cause of death. Oral squamous cell carcinoma (OSCC) represents the most frequent of all oral neoplasms. Many treatment modalities such as chemotherapy, radiotherapy, surgery, and immunotherapy are emerging but still, the patients' quality of life is questionable. Despite the advances in therapeutic approaches, the percentages of morbidity and mortality of OSCC have not improved significantly during the last 30 years. Treatment using natural products can act as a potent anti-cancer agent with reduced adverse effects. Cinnamic acid derivatives exhibit anti-cancer potential through histone deacetylase inhibitor (HDAC) enzyme inhibition. Methodology In an experimental study design, cinnamoyl hydroxamate derivatives were prepared. The structure was confirmed using ultraviolet-visible spectroscopy (UV-Vis), nuclear magnetic resonance (NMR), infrared spectroscopy, and mass spectrophotometry. An in-vitro antioxidant assay using nitric oxide scavenging and reducing power assay was done and an in-vitro cytotoxic (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay and viability assay were carried out using tryphan blue dye. Results Statistical analysis was performed using SPSS (IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp). Cinnamoyl hydroxamate derivatives were obtained and named as compounds 3a (E)-N-Hydroxy-3-(4-(N-(phenyl bromo) sulfamoyl) phenyl) acrylamide-) and 3b ((E)-N-Hydroxy-3-(4-(N-(phenyl nitro) sulfamoyl) phenyl) acrylamide). In the nitric oxide scavenging assay, compound 3a showed good antioxidant activity than 3b. Reducing power assay was higher in 3a compared to 3b. Cell viability using tryphan blue exhibited a concentration decrease in % cell viability with an increase in the concentration of human oral cavity squamous cell carcinoma cell line (OECM 1), a unique head and neck squamous carcinoma cell line (UM SCC 6) & human oral squamous cell carcinoma forming metastatic foci (HSC 3) cell lines. Conclusion The results of the present study revealed that the study compounds play a vital role in the up-regulation of apoptotic pathways and regulation of terminal differentiation pathways. The compounds showed good anti-oxidant and anti-cancer activities in lesser concentrations, hence they can be used as a therapeutic agent for oral squamous cell carcinoma.
ABSTRACT
Macrophages are important drug targets as they mediate a wide variety of infectious diseases. Visceral leishmaniasis (VL), schistosomiasis, brucellosis, and salmonellosis are some of the well-known infectious diseases in which macrophages play a prominent pathophysiological role. For instance, VL parasites exclusively house in the macrophages of liver and spleen. They are resistant to lysosomal degradation by unknown mechanisms, they survive and thrive safely within macrophages, they multiply, and they ultimately affect visceral organs, leading to severe pathological and sometimes even fatal conditions. The majority of routinely used drugs administered in free form distribute all over the body via systemic circulation, leading to relatively low therapeutic activity and a certain degree of toxicity. Unlike for nonmicrobial diseases, targeting parasites procuring resistance and ineffective therapeutic outcome can be obviously speculated in case of infectious disease. The preferential uptake by macrophages, intended to improve the balance between efficacy and toxicity, can be achieved by the use of nanomedicines, i.e. submicron-sized macromolecular or particulate drug delivery systems. This insight has stimulated researchers to use nanomedicines--which tend to be recognized by macrophages as 'foreign' and consequently are taken up by the intended target cells much more effectively than their free drug counterparts--to improve the treatment of infectious diseases. The literature reports extensively on such approaches; however, there are several constraints that limit the application of nanomedicine in macrophage-mediated drug targeting. Here, we briefly describe the strategies that are used to achieve effective drug targeting to macrophages, using VL as a model disease, and we also put forth an understanding of the most important limiting factors. Various physicochemical and biological factors used by researchers as reported in the literature are addressed, and the most important mechanisms and modes by which macrophage-specific drug targeting can be achieved are summarized. Based on the evidence obtained to date, it can be concluded that targeting macrophages is a valuable and validated strategy for improving the treatment of infectious diseases.
