The topic to this study is determination of mass spectrometric diffusion parameters “D_SD” of oligomeric associates of glycylhomopeptides and their Ag^I–complexes according to our “stochastic dynamic” approach and model equations under electrospray ionization condition. The problematic has recently gained attenion thanks to the latter formulas connecting among “D_SD” data; the measurable outcome “intensity” of analyte ions; and the experimental parameter “temperature,” respectively. The equations are empirically testable and verifiable. In advancing this innovative view upon which models we will carry out analysis of ions of oligomeric associates of peptides, we should point out that it is crucial to further test our formulas on a larger set of chemical classes and experimental conditions in order to verify their universal applicability to different mass spectrometric ionization methods. Because of, on the concept sketched above the D_SD parameters correlate excellent linearly with kinetic parameters of fragment reactions and quantum chemical diffusions according to the Arrhenius’s approximation which reflects the 3D molecular structures of analytes. The most important point regarding our concept is that it extends crucially the capability of the mass spectrometry of multidimentional structural analysis when is applied to high accuracy quantum chemical static and molecular dynamic approaches.

Tuberculosis and nosocomial infections are among the most frequent causes of death in the world. Mycobacteria such as Mycobacterium tuberculosis and ESKAPE bacteria are pathogens particularly implicated in these infectious diseases¹. The lack of antibiotics with novel mode of action associated with the spread of drug resistant bacteria make the fight against these infections particularly challenging.

Using antimicrobial peptides (AMPs) to restore or to broaden antibacterial activity of antibiotics is an interesting strategy to fight resistant strains. For example, the conjugation between chloramphenicol and ubiquicidine_29-41 gives a conjugate with increased activity against Escherichia coli and reduced toxicity against neutrophils compared to chloramphenicol alone ².

During previous work on the development of new anti-infective drugs, we identified a series of quinolines active against Gram-positive bacteria such as Staphylococcus aureus and Enterococcus faecalis. Concerning Gram-negative bacteria, some of them were active on E.coli but not against Pseudomonas aeruginosa^3,4. In order to broaden the antibacterial spectrum of this heterocycle core, we synthesized quinoline-based conjugates with short AMP sequences⁵. Their antibacterial activities against a panel of bacteria and mycobacteria will be discussed. Membranotropic properties study through tensiometry measures on bacterial mimetic membrane models was carried out to elucidate their mechanism of action.

References:

1. (a) WHO, Global tuberculosis report 2017; (b) Khan, H. A., Baig, F. K. & Mehboob. Nosocomial infections: Epidemiology, prevention, control and surveillance, Asian Pac. J. Trop. Biomed. 2017, 7, 478–482.
2. (a) Arnusch et al. Enhanced Membrane Pore Formation through High-Affinity Targeted Antimicrobial Peptides. PLoS ONE 2012 7:e39768; (b) Chen et al. Bacteria-Targeting Conjugates Based on Antimicrobial Peptide for Bacteria Diagnosis and Therapy. Mol. Pharm. 2015, 12, 2505.
3. Jonet, A.; Dassonville-Klimpt, A.; Sonnet, P.; Mullié, C. Side chain length is more important than stereochemistry in the antibacterial activity of enantiomerically pure 4-aminoalcohol quinoline derivatives. J. Antibiot. (Tokyo) 2013, 66, 683–686.
4. Laumaillé, Dassonville-Klimpt, Peltier, Mullié, Andréjak, Da-Nascimento, Castelain, Sonnet, Synthesis and study of new quinolineaminoethanols as anti-bacterial drugs, Pharmaceuticals 2019, 12(2), 91.
5. Strøm, M. B. et al. The Pharmacophore of Short Cationic Antibacterial Peptides, 2003, 46, 3–6.

Among the numerous imaging techniques, magnetic resonance imaging (MRI) has become the most powerful tool for diagnosis owing to its high spatial resolution, unlimited tissue penetration, and nonionizing nature. Nevertheless, one can mention its lack of sensitivity, which constitutes a major drawback especially in the field of molecular imaging. The combination of MRI and optical imaging (OI), detecting the luminescence emitted by a tracer, offers the high spatial resolution of the former and the high sensitivity of the latter. In this context, this study focused on the improvement of the relaxation properties of a commercial gadolinium chelate, Gd-HP-DO3A, bya non-covalent confinement of the complex in a semi-permeable nanosystem. To induce the bimodality, a fluorescent compound, i.e. ZW800-1, has been co-encapsulated inside the nanoparticle in a one-pot process. Thanks to their exceptional properties (i.e. biocompatibility, chemical stability, low toxicity) silica nanoparticles (SiO₂NPs) have been chosen as a matrix. Narrow size distribution SiO₂NPs were obtainedby a reverse microemulsion process (D_H: 80 nm). Relaxometric measurements of the synthesized nanoplatforms have proven its efficiency to decrease T_1,2of water proton molecules. The fluorescent properties were kept after the encapsulation of the fluorophore. The final system was characterized by Dynamic Light Scattering (DLS), Nuclear Magnetic Resonance (NMR) spectroscopy, relaxometry measurements, UV-Vis and IR spectroscopies and Transmission electron microscopy (TEM).

Objective

In the present study, a series of twenty benzotriazolyl-N-phenylalkylamide derivatives (7a-7j) and (8a-8j) were synthesized, characterized by physicochemical and spectral data (IR, ¹H NMR, ¹³C NMR and mass spectroscopy) and evaluated for their anti-HIV activity with the aim to develop novel substituted benzotriazole derivatives with broad-spectrum chemotherapeutic properties. The synthesized compound have been further evaluated as antibacterial and antifungal activity.

Method

A series of twenty benzotriazolyl-N-phenylalkylamide derivatives were synthesized by reacting substituted anilines (1) with 2-chloroacetyl chloride (2) and 3-chloropropionyl chloride (3) to form intermediate (4a-4j) and (5a-5j). Intermediates further reacted with benzotraizole (6) to form benzotriazolyl-N-alkylamide derivatives (7a-7j) and (8a-8j). The synthesized test compounds (7a-7j) and (8a-8j) were assessed by MTT colorimetric assay on C8166 cells and screened for antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (NCIM 2122), Bacillus subtilis (MTCC 121) and Gram-negative bacteria: Escherichia coli (MTCC118), Pseudomonas aeruginosa (MTCC 647), Salmonella typhi (NCIM 2501), Klebsiella pneumonia (MTCC 3384) and in vitro antifungal activity against Candida albicans (MTCC 227) and Aspergillus niger (NCIM 1056) by two fold broth serial dilution method.

Result- Compounds 7h, 7j, 8i and 8j being the most active showed therapeutic index that were >24.4, 31.1, 30.5 and 51.5 compared to Zidovudine (AZT) having therapeutic index (TI) 514342.6. The test compounds 7h, 7i, 7j, 8h, 8i and 8j exhibited very high activity against all the strains of Gram (+) ve and Gram (-) ve bacteria and antifungal strains.

Three Dimensional Printing (3D Printing) has been defined by ISO as “fabrication of objects through the deposition of a material using a print head, nozzle, or another printer technology”. 3D Printing has been trending in various disciplines from Science to Industry and Art. Being a tool of high precision and flexibility 3D Printing has been both recognized and challenged in the field of Medicinal Chemistry (MC).

The purpose of this poster is to provide an overview of the current and prospective applications and of the debatable aspects of the intersection between 3D Printing and MC.

This is a literature study. We have searched biomedical (Pubmed, Google Scholar) and tech – oriented (InTech) databases with key words (3D Printing, Medicinal Chemistry, considerations). We included studies authored in English or Greek and excluded studies declaring considerable conflict of interest.

The concept 3D Printing has appeared back in 1984. It took about ten years to print the first 3D Printed placebo tablet through the DOS method. In the next two decades 3D Printing related research has focused on tissue engineering. Nonetheless after 2010 various novelties have been developed enabling manufacturers to produce non-placebo drugs in a wealth of forms including tablets (orodispersable, floating, multicompartment etc), insulin and implants. 3D Printing can be categorized under three major variants; Powder solidification, Liquid solidification and Extrusion based systems.

It has been widely accepted that 3D Printing has the potential to revolutionize MC in terms of research and fabrication. Clinical trials can be considerably speeded up grace to the modifying properties of 3D Printing in pair with organ-in-a-chip technologies. Moreover pharmaceutical industry may be greatly altered given that 3D Printing will gradually enable single laboratories, pharmacists and potentially any trained individual to produce medication. The legibility of 3D Printing mediated clinical trials and the accessibility of 3D Printers are potential sources of controversy from a legal point of view.