These authors contributed equally to this work An antiparallel strand arrangement in water-soluble helicates creates an amphipathic functional topology akin to that of host-defence peptides. High and selective cancer cell line toxicity is exhibited, causing dramatic changes in the cell cycle without DNA damage, and remarkably there is no significant toxicity to MRSA and E. coli.

YesEnantiomers of a relatively rigid DNA-binding metallo-helix are shown to have comparable activity to that\ud of cisplatin against the cell lines MCF7 (human breast adenocarcinoma) and A2780 (human ovarian\ud carcinoma) but are ca five times more active against the cisplatin-resistant A2780cis. The cell-line\ud HCT116 p53+/+ (human colon carcinoma) is highly sensitive giving IC50 values in the nM range, far lower\ud than the cisplatin control. The hypothesis that the biological target of such metallohelices is DNA is\ud probed by various techniques. Tertiary structure changes in ct-DNA (formation of loops and\ud intramolecular coiling) on exposure to the compounds are demonstrated by atomic force microscopy\ud and supported by circular/linear dichroism in solution. Selectivity for 50-CACATA and 50-CACTAT\ud segments is shown by DNase I footprinting. Various three- and four-way oligonucleotide junctions are\ud stabilised, and remarkably only the L metallo-helix enantiomer stabilizes T-shaped 3WJs during gel\ud electrophoresis; this is despite the lack of a known helix binding site. In studies with oligonucleotide\ud duplexes with bulges it is also shown for the first time that the metallo-helix binding strength and the\ud number of binding sites are dependent on the size of the bulge. In contrast to all the above, flexible\ud metallo-helices show little propensity for structured or selective DNA binding, and while for A2780 the\ud cancer cell line cytotoxicity is retained the A2780cis strain shows significant resistance. For all\ud compounds in the study, H2AX FACS assays on HCT116 p53+/+ showed that no significant DNA damage\ud occurs. In contrast, cell cycle analysis shows that the DNA binders arrest cells in the G2/mitosis phase,\ud and while all compounds cause apoptosis, the DNA binders have the greater effect. Taken together\ud these screening and mechanistic results are consistent with the more rigid helices acting via a DNA\ud binding mechanism while the flexible assemblies do not

Among the hundreds of reported Achillea species, A. membranacea (Labill.) DC. is one of the six that grow in Jordan. Many species of this genus are used in folk medicine to treat a variety of ailments and several biological and pharmacological activities have been ascribed to their essential oil (EO). For this study, the EO obtained from a specimen of A. membranacea grown in Jordan was analyzed by GC-MS. Ninety-six compounds were detected, of which oxygenated monoterpenes was the predominant class (47.9%), followed by non-terpene derivatives (27.9%), while sesquiterpenes represented 14.2% of the total composition. The most abundant compound in the EO was 1,8-cineole (21.7%). The cytotoxic activity of the EO was evaluated against three cancer cell lines (MCF7, A2780 and HT29), and one normal fibroblast cell line (MRC5) by MTT assay. Significant growth inhibition was observed in EO-exposed A2780 and HT29 cells (IC50 = 12.99 and 14.02 μg/mL, respectively), while MCF7 and MRC5 were less susceptible. The EO induced apoptosis and increased the preG1 events in A2780 cells. 1,8-Cineole, the major constituent of the EO, exhibited submicromolar cytotoxicity against A2780 cells, and was 42 times more selective against MRC5 cells. Its cytotoxicity against A2780 cells was comparable with that of doxorubicin, but 1,8-cineole was more selective for MRC5 normal cells. Interestingly, 1,8-cineole enhanced apoptosis in A2780, and caused a remarkable dose-dependent increase in preG1 events. Thus, 1,8-cineole has demonstrated promising cytotoxic and proapoptotic properties.

One of the largest spontaneous adverse events reporting databases in the world is the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Unfortunately, researchers face many obstacles in analyzing data from the FAERS database. One of the major obstacles is the unstructured entry of drug names into the FAERS, as reporters might use generic names or trade names with different naming structures from all over the world and, in some cases, with typographical errors. Moreover, report duplication is a known problem in spontaneous adverse event-reporting systems, including the FAERS database. Hence, thorough text processing for database entries, especially drug name entries, coupled with a practical case-deduplication logic, is a prerequisite to analyze the database, which is a time- and resource-consuming procedure. In this study, we provide a clean, deduplicated, and ready-to-import dataset into any relational database management software of the FAERS database up to September 2021. Drug names are standardized to the RxNorm vocabulary and normalized to the single active ingredient level. Moreover, a pre-calculated disproportionate analysis is provided, which includes the reporting odds ratio (ROR), proportional reporting ratio (PRR), Chi-squared analysis with Yates correction (x2), and information component (IC) for each drug-adverse event pair in the database.