We have prepared a series of ten 3-arylcoumarin molecules, their respective fac-[Re(CO)3(bpy)L]+ and fac-[Re(CO)3(L⁀L)Br] complexes and tested all compounds for their antimicrobial efficacy. Whereas the 3-arylcoumarin ligands are virtually inactive against the human-associated pathogens with minimum inhibitory concentrations (MICs) > 150 μM, when coordinated to the fac-[Re(CO)3]+ core, most of the resulting complexes showed remarkable antibacterial potency. Several rhenium complexes exhibit activity in nanomolar concentrations against Gram-positive pathogens such as Staphylococcus aureus strains, including methicillin-resistant S. aureus (MRSA) and Enterococcus faecium. The molecules do not affect bacterial cell membrane potential, but some of the most potent complexes strongly interact with DNA, indicating it as a possible target for their mode of action. In vivo studies in the zebrafish model showed that the complexes with anti-staphylococcal/MRSA activity were non-toxic to the organism even at much higher doses of the corresponding MICs. In the zebrafish-MRSA infection model, the complexes increased the survival rate of infected fish up to 100% and markedly reduced bacterial burden. Moreover, all rescued fish developed normally following the treatments with the metallic compounds.
30 January 2024 in Applied Microbiology and Biotechnology
: The application of enzymes is expanding across diverse industries due to their nontoxic and biodegradable characteristics. Another advantage is their cost-effectiveness, reflected in reduced processing time, water, and energy consumption. Although Gram-positive bacteria, Bacillus, and Streptomyces spp. are successfully used for production of industrially relevant enzymes, they still lag far behind Escherichia coli as hosts for recombinant protein production. Generally, proteins secreted by Bacillus and Streptomyces hosts are released into the culture medium; their native conformation is preserved and easier recovery process enabled. Given the resilience of both hosts in harsh environmental conditions and their spore-forming capability, a deeper understanding and broader use of Bacillus and Streptomyces as expression hosts could significantly enhance the robustness of industrial bioprocesses. This mini-review aims to compare two expression hosts, emphasizing their specific advantages in industrial surroundings such are chemical, detergent, textile, food, animal feed, leather, and paper industries. The homologous sources, heterologous hosts, and molecular tools used for the production of recombinant proteins in these hosts are discussed. The potential to use both hosts as biocatalysts is also evaluated. Undoubtedly, Bacillus and Streptomyces spp. as production hosts possess the potential to take on a more substantial role, providing superior (bio-based) process robustness and flexibility. Key points: • Bacillus and Streptomyces spp. as robust hosts for enzyme production. • Industrially relevant enzyme groups for production in alternative hosts highlighted. • Molecular biology techniques are enabling easier utilization of both hosts.
1 October 2020 in European Journal of Medicinal Chemistry
Systemic toxicity and severe side effects are commonly associated with anticancer chemotherapies. New strategies based on enhanced drug selectivity and targeted delivery to cancer cells while leaving healthy tissue undamaged can reduce the global patient burden. Herein, we report the design, synthesis and characterization of a bio-inspired hybrid multifunctional drug delivery system based on diatom microalgae. The microalgae’s surface was chemically functionalized with hybrid vitamin B12-photoactivatable molecules and the materials further loaded with highly active rhenium(I) tricarbonyl anticancer complexes. The constructs showed enhanced adherence to colorectal cancer (CRC) cells and slow release of the chemotherapeutic drugs. The overall toxicity of the hybrid multifunctional drug delivery system was further enhanced by photoactivation of the microalgae surface. Depending on the construct and anticancer drug, a 2-fold increase in the cytotoxic efficacy of the drug was observed upon light irradiation. The use of this targeted drug delivery strategy, together with selective spatial–temporal light activation, may lead to lower effective concentration of anticancer drugs, thereby reducing medication doses, possible side effects and overall burden for the patient.
1 August 2018 in European Journal of Medicinal Chemistry
Sulfonamides represent the oldest synthetic antibacterial agents; however, their central position in controlling bacterial diseases has been seriously damaged by the development of widespread resistance. Herein, we revisited sulfathiazole, a commercial member of antibacterial sulfa drugs, intending to overcome sulfonamide resistance and identify new drug candidates through molecular modifications. We synthesized twelve sulfonamides (SA1–SA12) by replacing the amino group on the phenyl ring with various substituents and introducing a thiophene ring on the core scaffold of sulfathiazole. The obtained compounds and additionally two commercial sulfonamides, sulfathiazole and sulfadiazine, were extensively screened for their antimicrobial activities. The results indicated that new sulfonamides, unlike traditional ones, were selectively effective against various Staphylococcus aureus strains. Introducing a bulky lipophilic substituent at the para position of the phenyl ring significantly increased the antibacterial activities of the compounds against Staphylococcus aureus. The compounds demonstrating favourable selectivity indices were further evaluated for their membrane potential perturbation and DNA interaction properties. The obtained data showed that these are not supporting mechanisms for the antibacterial activities of the modified sulfathiazole derivatives. In order to rationalize the activity of the three most active compounds, SA7, SA11 and SA12, against S. aureus ATCC 25923, their binding hypotheses within the catalytic site of Staphylococcus aureus dihydropteroate synthase, the validated target enzyme of sulfonamides, were generated via molecular docking and further dissected using molecular dynamics simulations and dynamic 3D pharmacophores (dynophores).