Unprecedented anticancer activities of organorhenium sulfonato and carboxylato complexes against hormone-dependent MCF-7 and hormone-independent triple-negative MDA-MB-231 breast cancer cells.

Cisplatin and other metal-based drugs often display side effects and tumor resistance after prolonged use. Because rhenium-based anticancer complexes are often less toxic, a novel series of organorhenium complexes were synthesized of the types: XRe(CO)3Z (X = α-diimines and Z = p-toluenesulfonate, 1-naphthalenesulfonate, 2-naphthalenesulfonate, picolinate, nicotinate, aspirinate, naproxenate, flufenamate, ibuprofenate, mefenamate, tolfenamate, N-acetyl-tryptophanate), and their biological properties were examined. Specifically, in hormone-dependent MCF-7 and hormone-independent triple-negative MDA-MB-231 breast cancer cells, the p-toluenesulfonato, 1-naphthalenesulfonato, 2-naphthalenesulfonato, picolinato, nicotinato, acetylsalicylato, flufenamato, ibuprofenato, mefenamato, and N-acetyl-tryptophanato complexes were found to be far more potent than conventional drug cisplatin. DNA-binding studies were performed in each case via UV-Vis titrations, cyclic voltammetry, gel electrophoresis, and viscosity, which suggest DNA partial intercalation interaction, and the structure-activity relationship studies suggest that the anticancer activities increase with the increasing lipophilicities of the compounds, roughly consistent with their DNA-binding activities.

DNA-binding and cytotoxic efficacy studies of organorhenium pentylcarbonate compounds.

Seven organorhenium pentylcarbonate compounds (PC1-PC7) have been synthesized. DNA-binding studies of the PC-series compounds using electronic spectroscopy and gel electrophoresis suggest that the compounds presumably bind to DNA in an intercalative mode. The intrinsic binding constants for PC4, PC6, and PC7 were found to be 1.6 × 10(4), 3.9 × 10(4), and 4.2 × 10(4) M(-1), respectively. The X-ray structure determinations and density functional theory calculations indicate that the polypyridyl ligands in the compounds are nearly planar facilitating DNA binding through an intercalation mechanism. Cytotoxicity studies of 10 µM pentylcarbonate compounds against HTB-12 human astrocytoma brain cancer cells were studied for 48 h. It was observed that each of the pentylcarbonate compounds is active against the cancer cells. However, under analogous conditions, CRL-2005 rat astrocyte normal brain cells are not affected significantly.

Epigenome-wide association study of prostate cancer in African American men identified differentially methylated genes.

INTRODUCTION: Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. METHODS: This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome-wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. RESULTS: Around 5,139 differentially methylated CpG-sites (q < 0.01, lΔßl > 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors.  Multiple representative differentially methylated regions (DMRs), including immune-related genes, such as CD40, Galectin3, OX40L, and STING, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors' total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG-sites (q < 0.05, lΔßl > .05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1, S100A2, ITGA4, HLA-C, and ADCYAP1, have previously been linked to tumor progression in PCa. CONCLUSION: Several differentially methylated genes involved in immune-oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American-specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.

Similarity Studies of Corona Viruses through Chaos Game Representation.

The novel coronavirus (SARS-COV-2) is generally referred to as Covid-19 virus has spread to 213 countries with nearly 7 million confirmed cases and nearly 400,000 deaths. Such major outbreaks demand classification and origin of the virus genomic sequence, for planning, containment, and treatment. Motivated by the above need, we report two alignment-free methods combing with CGR to perform clustering analysis and create a phylogenetic tree based on it. To each DNA sequence we associate a matrix then define distance between two DNA sequences to be the distance between their associated matrix. These methods are being used for phylogenetic analysis of coronavirus sequences. Our approach provides a powerful tool for analyzing and annotating genomes and their phylogenetic relationships. We also compare our tool to ClustalX algorithm which is one of the most popular alignment methods. Our alignment-free methods are shown to be capable of finding closest genetic relatives of coronaviruses.

Application of nanotechnology in cancer.

Nanotechnology refers broadly to a field of applied science and technology whose unifying theme is the control of matter on the molecular level in scales smaller than 1 micrometer, normally 1 to 100 nanometers, and the fabrication of devices within that size range. In the last five years this technology has been improved tremendously in disease diagnosis and prognosis and maximum research and clinical work has been completed in cancer. The use of various pharmaceutical nanocarriers has become one of the most important areas of nanomedicine. Novel nanotechnologies can complement and augment existing genomic and proteomic techniques to analyze variations across different tumor types, thus offering the potential to distinguish between normal and malignant cells. Sensitive biosensors constructed of nanoscale components (e.g., nanocantilevers, nanowires, and nanochannels) can recognize genetic and molecular events and have reporting capabilities, thereby offering the potential to detect rare molecular signals associated with malignancy. Such signals may then be collected for analysis by nanoscale harvesters that selectively isolate cancer-related molecules from tissues. The implication of nanotechnology in cancer is discussed in this article with an emphasis on biomarker detection, imaging studies for diagnosis, and its role in therapeutic intervention.

The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines.

PURPOSE: Because of the scarcity of suitable brain cancer drugs, researchers are frantically trying to discover novel and highly potent drugs free of side effects and drug-resistance. Rhenium compounds are known to be nontoxic and exhibit no drug resistance. For that reason, we have developed a series of novel rhenium acetylsalicylato (RAC or ASP) complexes to test their cytotoxicity on brain cancer cells. Also we have attempted to explore the DNAbinding properties of these compounds because many drugs either directly or indirectly bind to DNA. METHODS: We have treated the RAC series compounds on human astrocytoma brain cancer cell lines and rat normal brain astrocyte cells and determined the efficacy of these complexes through in vitro cytotoxicity assay. We carried out the DNA-binding study through UV titrations of a RAC compound with DNA. Also we attempted to determine the planarity of the polypyridyl ligands of the RAC series compounds using DFT calculations. RESULTS: RAC6 is more potent than any other RAC series compounds on HTB-12 human astrocytoma cancer cells as well as on Glioblastoma Multiforme D54 cell lines. In fact, The IC-50 value of RAC6 on HTB-12 cancer cells is approximately 2 µM. As expected, the RAC series compounds were not active on normal cells. The DFT calculations on the RAC series compounds were done and suggest that the polypyridyl ligands in the complexes are planar. The UV-titrations of RAC9 with DNA were carried out. It suggests that RAC9 and possibly all RAC series compounds bind to minor grooves of the DNA. CONCLUSION: Because of the very low activity of RAC6 on normal cells and low lC50 value of on astrocytoma (HTB-12) cell lines, it is possible that RAC6 and its derivatives may potentially find application in the treatment of brain cancers. The DFT calculations and UV titrations suggest that RAC series compounds either bind to DNA intercalatively or minor grooves of the DNA or both. However, it is highly premature to make any definite statement in the absence of other techniques.

Anticancer Properties of Novel Rhenium Pentylcarbanato Compounds against MDA-MB-468(HTB-132) Triple Node Negative Human Breast Cancer Cell Lines.

AIM: To study the efficacy of novel rhenium compounds to treat triple node negative breast cancer. PLACE AND DURATION: Six (6) novel rhenium pentycarbanato compounds (PC1-6) were synthesized and triple node negative breast cancer cell lines HTB-132 and Balb/c mouse kidney cell lines were treated with each of them for 48 hours. The results were analyzed by a common trypan blue cell death assay system and statistically analyzed. PLACE AND DURATION: The compounds were synthesized, analyzed and evaluated at the Department of Chemistryof Morgan State University, Baltimore, Maryland and the Pharmaceutical Sciences Department of Elizabeth City State University campus of the University of North Carolina system. METHODOLOGY: The novel rhenium compounds were synthesized from one-pot reactions of Re2(CO)10 with the corresponding α-diimine ligands in 1-pentanol.The compounds were characterized spectroscopically. The cell lines were cultured by standard cell culture procedure and treated with each of the six compounds in DMSO for 48 hours with a negative control and a DMSO vehicular control along with a cisplatin positive control.The cytotoxicity was evaluated by standard trypan blue assay and the results were statistically analyzed. RESULTS: The trypan blueassay reveals that these compounds have significant cytotoxicity against MDA-MB-468 (HTB-132) triple node negative breast cancer cell lines and are less nephrotoxic than cisplatin. CONCLUSION: The novel rhenium compounds PC 1-6 can potentially find applications in the treatment of highly malignant triple node negative breast cancer.

The effect of novel rhenium compounds on lymphosarcoma, PC-3 prostate and myeloid leukemia cancer cell lines and an investigation on the DNA binding properties of one of these compounds through electronic spectroscopy.

Despite the tremendous success of cisplatin and other platinum-based anticancer drugs, severe toxicity and resistance to tumors limit their applications. It is believed that the coordination (formation of covalent bond) of the metal (platinum) to the nitrogen bases of DNA cause the ruptures of the cancer as well as normal cells. A search for anticancer drugs with different modes of action resulted in the synthesis of variety of novel compounds. Many of them are in clinical trials now. Recently we synthesized a series of novel rhenium pentylcarbonato compounds (PC1-PC6). The rhenium atom in each compound is coordinated (bonded) to a planar polypyridyl aromatic ligand, thereby forcing each compound to intercalate between the DNA bases. We have investigated the DNA binding properties of one of the PC-series of compounds (PC6) using electronic spectroscopy. The UV absorption titration of PC6 with DNA shows hypochromic effect with concomitant bathochromic shift of the charge transfer band at 290 nm. These results suggest that the compound PC6 binds to DNA through intercalation. It is therefore likely that the other PC-series of compounds will behave in a similar manner. Thus it is expected that these compounds will exhibit negligible or no side effect. We have observed that the PC-series of compounds are strong cytotoxic agents against lymphosarcoma (average GI50 ≈ 2±2.6 µM), PC-3 prostate (average GI50 ≈ 3±2.8 µM) and myeloid leukemia (average GI50 ≈ 3±2.8 µM) cancer cell lines. The average GI50 values of the PC-series of compounds are 2-3 less than the corresponding GI50 values of cisplatin. Also each of the PC-series of compounds exhibits less toxicity than cisplatin in the glomerular mesangial cells.