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Acyclovir (ACV) is a promising candidate for drug repurposing because of its potential to provide an effective treatment for viral infections and non-viral diseases, such as cancer, for which limited treatment options exist. However, its poor physicochemical properties limit its application. This study aimed to formulate and evaluate an ACV-loaded red clay nanodrug delivery system exhibiting an effective cytotoxicity. The study focused on the preparation of a complex between ACV and red clay (RC) using sucrose stearate (SS) (nanocomplex F1) as an immediate-release drug-delivery system for melanoma treatment. The synthesized nanocomplex, which had nanosized dimensions, a negative zeta potential and the drug release of approximately 85% after 3 h, was found to be promising. Characterization techniques, including FT-IR, XRD and DSC-TGA, confirmed the effective encapsulation of ACV within the nanocomplex and its stability due to intercalation. Cytotoxicity experiments conducted on melanoma cancer cell lines SK-MEL-3 revealed that the ACV release from the nanocomplex formulation F1 effectively inhibited the growth of melanoma cancer cells, with an IC50 of 25 ± 0.09 µg/mL. Additionally, ACV demonstrated a significant cytotoxicity at approximately 20 µg/mL in the melanoma cancer cell line, indicating its potential repurposing for skin cancer treatment. Based on these findings, it can be suggested that the RC-SS complex could be an effective drug delivery carrier for localized cancer therapy. Furthermore, the results of an in silico study suggested the addition of chitosan to the formulation for a more effective drug delivery. Energy and interaction analyses using various modules in a material studio demonstrated the high stability of the composite comprising red clay, sucrose stearate, chitosan and ACV. Thus, it could be concluded that the utilization of the red clay-based drug delivery system is a promising strategy to improve the effectiveness of targeted cancer therapy.

Laryngeal carcinoma, the most common among head and neck squamous cell carcinoma (HNSCC) induces 1% of all cancer deaths. Curcumin, the active constituent of turmeric is more effective in the treatment of various cancer. In the present study, with an aim to explore the mechanistic role of BDMC-A as a chemotherapeutic agent, we have investigated the inhibitory effect of BDMC-A on invasion, angiogenesis, and metastasis in Hep-2 cells and compared it with curcumin. Curcumin and BDMC-A treated Hep-2 cells were quantified using western blotting and RT-PCR technique to investigate the effect of Curcumin and BDMC-A on transcription factors involved in signal transduction cascade, invasion and angiogenesis associated markers. Pro-inflammatory markers of curcumin and BDMC-A treated Hep-2 cells were estimated using the ELISA kit. The results showed that BDMC-A might exhibit the anti-cancer activity by inhibiting transcription factors mainly NF-κB, p65, c-Jun, c-Fos, STAT3, 5, PPAR-γ and β-catenin, which are responsible for tumor progression and malignancy. Downregulation of MMP-9, VEGF, IL-6 and IL-8 and upregulation of TIMP-2 levels further supports the anti-tumor potential of BDMC-A. Our overall results revealed that BDMC-A more effectively inhibited the markers of invasion, angiogenesis and metastasis in comparison with curcumin.

PURPOSE: Lung cancer is the most commonly diagnosed and leading cause of cancer death worldwide. Imidazo-benzamides are considered to be good anti-cancer agents. The present study was aimed to investigate the cytotoxicity of a novel imidazo-benzamide derivative N-(2-(3-(tert-butyl)ureido)ethyl)-4-(1H-imidazol-1-yl)benzamide (TBUEIB) in lung cancer cell line A549. METHODS: The antiproliferative activity of TBUEIB was investigated using MTT, LDH and trypan blue assay. The apoptotic potential was investigated using various staining techniques and further confirmed by DNA fragmentation assay and western blotting. RESULTS: TBUEIB inhibited fifty precent A549 cells at a dose of 106 μM. The novel compound was found to exert a modulatory effect on apoptotic marker caspase-3 as well as epigenetic regulatory proteins like DNA Methyltransferase 1 (DNMT1). In silico studies with the compound and other epigenetic proteins such as Histone deacetylase (HDAC) and ubiquitin-like with PHD (plant homeodomain) and RING (Really Interesting New Gene) finger domains 1(UHRF1) showed good modulatory effects. CONCLUSION: The overall results obtained in the study conclude that the novel compound TBUEIB has potential anti-cancer activities, mainly by targeting the expression of DNMT1 enzyme, which may have re-activated the major tumor suppressor genes involved in the cell cycle, leading to the apoptosis of the cancer cells. The results also indicate that the compound has more than one target in the epigenetic pathway implying that the compound may be a potential multi-target compound. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40199-021-00419-3.

Amphotericin B (AmB), a hydrophobic drug with negligible aqueous solubility was conjugated to bovine serum albumin (BSA) via amide bond coupling to give 6 to 8 wt% drug payload. The resulting conjugate was characterized using SDS-PAGE and UV-visible, FTIR and CD spectroscopy. The conjugate was water-soluble to the extent of 150 mg/ml, was non-toxic to HEK 293 T cells at a concentration of 500 μg/ml (equivalent to ~30 μg AmB) and showed hemolysis of5% at 200 μg/ml (equivalent to ~12 μg AmB) against human erythrocytes in vitro. In vitro release studies at 37 °C demonstrated steady release of AmB up to 20% from the conjugate with little burst effect in phosphate buffered saline whereas thrice the amount was released in human plasma in 72 h. AmBisome® used as a reference showed a very similar release profile in plasma. The conjugate exhibited potential anti-fungal activity against yeast strains such as C. albicans, C. neoformans and C. parapsilosis with the minimum inhibitory concentration (MIC) equivalent to AmB ranging from 0.7 to 1.1 μg/ml while AmBisome® and AmB alone showed the MIC between 0.78 and 1.5 and 0.53-0.78 μg/ml respectively. Although AmB has been conjugated to various natural and synthetic polymers to improve its solubility and reduce its toxicity, the results obtained in this study using the model protein BSA as a carrier point to the possibility of taking this pro-drug approach to human clinical use using human serum albumin (HSA) as the carrier, since HSA has emerged as a versatile drug carrier for treating diabetes and cancer and improving the pharmacokinetic profile of many drugs with US FDA approving HSA as a drug carrier for the anti-cancer drug paclitaxel (Abraxane®) for human use.

Novel eco-friendly methods for the synthesis of metal nanoparticles are preferred and have recently been widely researched. In this study, a cost-effective and environmentally friendly method for the synthesis of gold nanoparticles was investigated. Costus pictus, also known as insulin plant due to its antidiabetic activity, was used as the reducing agent. Chloroaurate ions were rapidly reduced by the methanolic extract of Costus pictus, which was indicated by the color change from yellow to ruby red. The presence of a peak at 530 nm in UV-visible spectrophotometry confirmed the reduction of chloroaurate to gold nanoparticles. The reaction kinetics and effects of time, temperature, concentration of extract and substrate were also studied. The size and morphology of gold nanoparticles were analyzed using scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HR-TEM) and they were found to be cuboidal, with a size of around 20 nm. The size of the particles was also analyzed by the particle size analyzer, and was found to be 45 nm. These particles were functionalized with bisdemethoxycurcumin analog (BDMCA). X-ray diffraction (XRD) analysis of prepared nanoparticles showed that the gold nanoparticles have a face centered cubic structure and that of functionalized nanoparticles showed peaks similar to that of BDMCA. Fourier transform infrared spectroscopy (FTIR) studies revealed the presence of reducing groups in the plant methanolic extract and the functionalization of nanoparticles with BDMCA was also confirmed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that, the BDMCA-functionalized gold nanocubes possess anticancer activity. The mechanism of action is discussed.

The present study deals with the toxicity assessment of NBDMCA in vitro using red cell model and in vivo using rat model. Hemolysis was used as toxicity index in red blood cells. Different concentrations of NBDMCA viz. , 20, 40, 60, 80, 100 μg/ml in PBS were incubated with the red blood cells of rat. NBDMCA was found to induce less than 3% hemolysis in intact erythrocytes which was far lesser than the accepted threshold of 5%. Hematological cum biochemical parameters along with histopathological analysis and hemolysis were used as toxicity indices in rats. Whole blood of the NBDMCA-treated rats and control rats were analyzed for hematological parameters: erythrocyte count, leukocyte count, leukocyte differential count, hemoglobin, hematocrit, mean cell volume (MCV), mean corpuscular hemoglobin (MCH) using fully automated hematology analyzer. All hematological parameters analyzed were within the normal values in both the groups. Plasma samples were analyzed for biochemical parameters including glucose, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine (Cre), albumin (Alb), total protein (TP), calcium (Ca) and phosphorus (P) using fully automated biochemistry analyzer. Invariably, all the biochemical parameters are significantly similar in both the groups. Gross examination of vital organs like lung, heart, kidney, spleen and brain reveals no detectable abnormalities in NBDMCA-treated animals. Internal organs like heart, brain, lung, liver, spleen and kidneys of the experimental animals were collected and fixed in 10% formalin, processed in vacuum infiltration tissue processor, embedded with paraffin wax and sectioned at approximately 5 μm thick, stained with hematoxylin and eosin. The sections were examined and imaged through light microscopy. NBDMCA did not produce any significant changes in the histoarchitecture of all the organs studied. Heart, aorta, brain, lung, liver, kidney and spleen showed normal pathology report. The histopathological data correlated with the biochemical results indicating normal hepatocellular and nephrotic function. Our investigation clearly revealed that NBDMCA is hemocompatible in vitro and also safe to vital organs in vivo . We conclude that NBDMCA is non-toxic and safe and can be promoted as an ideal therapeutic tool for human use.

We have investigated the time-dependent effect of multi-walled carbon nanotubes (MWCNTs) in rats upon single inhalation exposure followed by intermittent sacrifice. The effects were monitored by analyzing the bronchoalveolar lavage fluid (BALF) and histopathological analysis. Cell count, neutrophils, lymphocytes, lactate dehydrogenase, alkaline phosphatase, protein and cytokines (tumor necrosis factor-alpha (TNF-?) and interleukin 4 (IL-4)) were significantly increased, while cell viability and alveolar macrophage count significantly decreased in the BALF of MWCNT-treated rats on day 1, day 7 and day 14 post-exposure, when compared to control rats. Histopathological analysis revealed inflammation, fibrosis and granuloma in the lungs of MWCNTs-treated rats on day 7 and day 14 post-exposure. We interpret that MWCNT induces inflammation, fibrosis and granuloma characterized by progressive elevation of TNF-? and IL-4. Histopathological studies further support our view and reveal the distribution of MWCNT in lungs and tracheobronchial lymph nodes (TBLN). We conclude that MWCNT-induced pulmonary toxicity is considerable even on single exposure. � 2015 The Authors.