Synthesis and Biological Activity of Fused tetracyclic Pyrrolo[2,1-C][1,4]Benzodiazepines

Cancer remains the second major cause of death in the world. Thus, there is a pressing need to identify potential synthetic route for the development of novel anticancer agents which will serve as lead compounds to effectively combat this life-threatening epidemic. Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) have sparked a great interest as lead compounds because of their cancerostatic and anti-infective properties. The twisted molecular structure of PBD analogs provides both helical and chiral elements. In an effort to expand novel PBDs that interact with the key exocyclic amino group of the DNA-guanine base, we hypothesized that construction of a fused cyclic active system, would likely serve as an electrophilic site when compared to traditional electrophilic C11-N10 imine group. To examine our theory, we report herein the synthesis and cell viability/cytotoxicity of a series of PBD analogs using NCI-60 cell lines screening. Thus, compounds 1–13 were synthesized and fully characterized. The selected PBDs were found to have marginal inhibition of growth, up to 30%, for certain cell lines

1J: Effect of Brominated Indole-3-carboxaldehydes on the Communication and Biofilm Formation in Bacteria

Quorum sensing (QS) is a type of intercellular communication used by many bacterial species wherein bacteria produce and secrete signaling molecules to affect changes in bacterial populations. As the population of bacteria grows, the concentration of signaling molecules secreted also increases in the environment. Once the signaling molecules reach a threshold concentration, the molecules saturate their respective receptors on, or in, the bacteria altering gene expression. Indole is an organic compound that serves to mediate communication among many bacteria and it has been shown to affect a wide variety of bacterial behaviors including biofilm formation, antibiotic resistance, and the production of virulence factors. Therefore, targeting indole signaling may be a way to mediate pathogenicity among bacteria without the use of traditional antibiotics. In this study, we used a model bacterium Chromobacterium violaceum to investigate a subset of indole derivatives, and we identify three new quorum sensing inhibitors: 5, 6, and 7-bromoindole-3-carboxaldehydes. We further show that bromination of indole-3-carboxaldehyde significantly increased the potency of quorum sensing inhibition. In addition, we evaluated the impact of those molecules on biofilm formation in the pathogenic species Pseudomonas aeruginosa

Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) compounds as inhibitors of quorum sensing and biofilm formation

With the rise in antibiotic resistance, quorum sensing inhibition has emerged as a possible alternative to classical antibiotic therapy. Quorum sensing is density-dependent communication between bacteria that allows the bacteria to coordinate gene expression. This communication is accomplished through the secretion of certain signal molecules, and is often responsible for the development of pathogenicity in bacteria. By inhibiting this communication, bacteria may be prevented from expressing pathogenic traits, such as biofilm formation. In this study, 12 novel Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) compounds were tested for their ability to inhibit quorum sensing using disk diffusion assays. Blank disks were loaded with the PBD compounds and overlaid with molten agar inoculated with Chromobacterium violaceum. C. violaceum is a quorum sensing indicator species. The bacteria produce a purple pigment when they undergo quorum sensing but turn white when quorum sensing is inhibited. Compounds that showed quorum sensing inhibition were then tested for the inhibition of biofilm formation. Of the 12 PBD compounds, three were determined to be QSIs. We further tested two of these, compounds 17 and 33, for their ability to inhibit biofilm formation at different concentrations. Using spectrophotometry, where a lower absorbance indicated greater quorum sensing inhibition, these compounds were also identified as biofilm inhibitors in C. violaceum. Further testing is needed to determine whether the inhibition of biofilms observed is due to quorum sensing inhibition or growth inhibition. If the inhibition of biofilms is due to inhibition of quorum sensing, future studies may determine the mechanism of inhibition

Effect of Bromination on the Quorum Sensing-Inhibiting Properties of Indole-3-Carboxaldehydes in <i>Chromobacterium violaceum</i> AHL System

Quorum sensing (QS) is a form of bacterial communication involved in the production of virulence factors in many species. As a result, inhibition of quorum sensing may be of use in mitigating pathogenesis. The signaling molecule indole is currently being investigated as a target for quorum sensing inhibition (QSI) and the indole derivative indole-3-carboxaldehyde (ICA) has been shown to inhibit quorum sensing-mediated behaviors in Escherichia coli. In this study, we investigate bromination as a method of increasing the QSI capabilities of indole carboxaldehydes. The IC50 values of three monobrominated indole carboxaldehydes (5-bromoindole-3-carboxaldehyde, 6-bromoindole-3-carboxaldehyde, and 7-bromoindole-3-carboxaldehyde) were determined and compared to the IC50 value of ICA. The bromination of these indole carboxaldehydes reduced the IC50 values between 2- and 13-fold, indicating that bromination significantly increases the potency of these indole carboxaldehydes

#16 - The Effect of Kinesio Tapes on the Growth of Staphylococcus aureus ATTC 12600

Kinesio tapes are adhesive tapes used in physical therapy to alleviate discomfort and facilitate lymphatic drainage by minimally lifting the skin. It is believed that kinesio tapes reduce inflammation, prevent injuries, and promote circulation. However, in order to achieve these effects, these tapes are often worn in contact with the skin for several consecutive days with the producers of these tapes stating that they are hypoallergenic and wearable as such. Such prolonged skin exposure may impact the skin microbiota and may promote local skin infections, especially if abrasions form under the tape, as cases of MRSA infections have been reported in athletes wearing these tapes for prolonged periods. Further, among the nine tapes whose literature we have investigated, only one was indicated as having “antimicrobial” properties. For these reasons, the effect of kinesio tapes on skin microbiota should be evaluated. In this study, we studied the effect of nine of these kinesio tapes on the growth of Staphylococcus aureus (ATTC 12600) in a standard diffusion-based assay. Lawns of bacteria were prepared and one square centimeter pieces of tape were placed on the agar for 24 hours. Both the adhesive and the backing of each tape were evaluated for their antimicrobial properties. Upon evaluation, it was observed that none of the tapes caused formation of inhibition zones, including the tape that was claimed to possess antimicrobial properties. However, the adhesive material present on all the studied tapes inhibited the growth of S. aureus. These results indicate that the glue used on kinesio tapes has a potential to impact the normal skin microbiota. Further, extended exposure to the tape could lead to significant changes in normal skin microbiota, which might contribute to an increased risk of skin infections such as the MRSA infections previously reported

Analysis of Bacteria Found in Ball Pits Located in Clinical Settings

Ball pits are often used in rehabilitation clinics by physical therapists and other rehabilitation professionals for various reasons. Previous research has shown that many seemingly inconspicuous objects in hospital settings can be fomites, or nonliving disease-carrying agents, that are particularly dangerous in hospitals due to a high density of immunocompromised individuals. We sought to find out how much bacteria can be carried in ball pits and if any of the bacteria found could be potential opportunistic pathogens. We also wanted to know whether the material that the balls were made from had an effect on either of the variables. We collected samples from the pit itself and a number of balls within the pit. Samples from balls made from both foam material and plastic were obtained. Surfaces were swabbed with sterile swabs for 30 seconds, then sealed and brought back to the UNG Biology Department for analysis. Samples were plated on tryptic soy agar (TSA) and incubated at 33 ̊C for 24 hours. Plates were then removed, examined, counted, and individual colonies were identified using the Biolog GEN III Bacterial Identification System. Opportunistic pathogens such as Streptococcus sobrinus, Bacillus mojavensis/subtilis, Mycobacterium novocastrense, Staphylococcus aureus, and Aerococcus viridans were identified

Synthesis and biological activity of fused tetracyclic Pyrrolo[2,1-c][1,4]benzodiazepines

Cancer remains the second major cause of death in the world. Thus, there is a pressing need to identify potential synthetic route for the development of novel anticancer agents which will serve as lead compounds to effectively combat this life-threatening epidemic. Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) have sparked a great interest as lead compounds because of their cancerostatic and anti-infective properties. The twisted molecular structure of PBD analogs provides both helical and chiral elements. In an effort to expand novel PBDs that interact with the key exocyclic amino group of the DNA-guanine base, we hypothesized that construction of a fused cyclic active system, would likely serve as an electrophilic site when compared to traditional electrophilic C11-N10 imine group. To examine our theory, we report herein the synthesis and cell viability/cytotoxicity of a series of PBD analogs using NCI-60 cell lines screening. Thus, compounds 1–13 were synthesized and fully characterized. The selected PBDs were found to have marginal inhibition of growth, up to 30%, for certain cell lines