Identification and characterization of antibacterial compound(s) of cockroaches (Periplaneta americana)

Infectious diseases remain a significant threat to human health, contributing to more than 17 million deaths, annually. With the worsening trends of drug resistance, there is a need for newer and more powerful antimicrobial agents. We hypothesized that animals living in polluted environments are potential source of antimicrobials. Under polluted milieus, organisms such as cockroaches encounter different types of microbes, including superbugs. Such creatures survive the onslaught of superbugs and are able to ward off disease by producing antimicrobial substances. Here, we characterized antibacterial properties in extracts of various body organs of cockroaches (Periplaneta americana) and showed potent antibacterial activity in crude brain extract against methicillin-resistant Staphylococcus aureus and neuropathogenic E. coli K1. The size-exclusion spin columns revealed that the active compound(s) are less than 10 kDa in molecular mass. Using cytotoxicity assays, it was observed that pre-treatment of bacteria with lysates inhibited bacteria-mediated host cell cytotoxicity. Using spectra obtained with LC-MS on Agilent 1290 infinity liquid chromatograph, coupled with an Agilent 6460 triple quadruple mass spectrometer, tissues lysates were analyzed. Among hundreds of compounds, only a few homologous compounds were identified that contained isoquinoline group, chromene derivatives, thiazine groups, imidazoles, pyrrole containing analogs, sulfonamides, furanones, flavanones, and known to possess broad-spectrum antimicrobial properties, and possess anti-inflammatory, anti-tumour, and analgesic properties. Further identification, characterization and functional studies using individual compounds can act as a breakthrough in developing novel therapeutics against various pathogens including superbugs

Synthesis and molecular modelling of thiadizole based hydrazone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitory activities.

Some novel substituted thiazolylhydrazine derivatives were designed, synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes and antioxidant activities were investigated. The structures of the synthesized compounds were determined using different spectroscopic techniques such as H-1-NMR, C-13-NMR, and HRMS. According to the enzyme inhibition results, the synthesized compounds showed selectivity against BuChE enzyme inhibition. Compounds 5e, 5g, 5i and 5j displayed significant BuChE inhibition potencies. Among them, compound 5i was found to be the most effective derivative with an IC50 value of 56.01 +/- 0.054 mu M. In addition, their antioxidant properties were evaluated in vitro through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. For compounds 5e, 5g, 5i and 5j in silico molecular docking and 100 ns molecular dynamics simulations studies against the BuChE enzyme were performed to determine possible protein-ligand interactions and stability. DFT-D3 study was performed to stabilize of compounds 5e, 5g, 5i and 5j both in gas and solvent medium and investigated their electronic properties. Of all geometries, that of DMSO is the lowest one