With the significant increase of patients suffering from different types of cancer, it is evident that prompt measures in the development of novel and effective agents need to be taken. Pyrrole moiety has been found in various active compounds with anti-inflammatory, antiseptic, antibacterial, lipid-lowering and anticancer properties. Recent advances in the exploration of highly active and selective cytotoxic structures containing pyrrole motifs have shown promising data for future investigations. Accordingly, this review presents an overview of recent developments in the pyrrole derivatives as anticancer agents, with a main focus towards the key moieties required for the anti-tumor activities. Pyrrole molecules comprising prominent targeting capacities against microtubule polymerization, tyrosine kinases, cytochrome p450 family 1, histone deacetylase and bcl-2 proteins were reported. In addition, several mechanisms of action, such as apoptosis, cell cycle arrest, inhibiting kinases, angiogenesis, disruption of cell migration, modulation of nuclear receptor responsiveness and others were analyzed. Furthermore, in most of the discussed cases we provided synthesis schemes of the mentioned molecules. Overall, the utilization of pyrrole scaffold for the design and synthesis of novel anticancer drugs could be a promising approach for future investigations.

With the significant growth of patients suffering from neurodegenerative diseases (NDs), novel classes of compounds targeting monoamine oxidase type B (MAO-B) are promptly emerging as distinguished structures for the treatment of the latter. As a promising function of computer-aided drug design (CADD), structure-based virtual screening (SBVS) is being heavily applied in processes of drug discovery and development. The utilization of molecular docking, as a helping tool for SBVS, is providing essential data about the poses and the occurring interactions between ligands and target molecules. The current work presents a brief discussion of the role of MAOs in the treatment of NDs, insight into the advantages and drawbacks of docking simulations and docking software, and a look into the active sites of MAO-A and MAO-B and their main characteristics. Thereafter, we report new chemical classes of MAO-B inhibitors and the essential fragments required for stable interactions focusing mainly on papers published in the last five years. The reviewed cases are separated into several chemically distinct groups. Moreover, a modest table for rapid revision of the revised works including the structures of the reported inhibitors together with the utilized docking software and the PDB codes of the crystal targets applied in each study is provided. Our work could be beneficial for further investigations in the search for novel, effective, and selective MAO-B inhibitors.

Considering the complex pathogenesis of Alzheimer’s disease (AD), the multitarget ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target approach. Thus, a series of 13 novel (5e-q) pyrrole-based Schiff bases were synthesized by conventional and microwave-assisted condensations, and the compounds were evaluated for MAO-A, MAO-B and AChE inhibitory activities. The chemical structures of the newly formed molecules were elucidated by a combination of spectral methods. The obtained results confirmed the theoretical data. The majority of the title Schiff bases demonstrated good potential towards AChE at 10 μM concentrations, with the most promising compound 5m (58%) exerting a comparative effect to that of the applied standard—Donepezil. 5j and 5o selectively inhibited MAO-B by 26% and 21% (at 1 μM concentration), respectively. The compound condensed with 5-nitro-2-furaldehyde (5j) achieved the best dual MAO-B and AChE inhibitory capacities. In addition to the in vitro analysis, docking simulations targeting the active sites of AChE (PDB ID: 4EY6) and MAO-B (PDB: 2V5Z) were employed to explore the possible interactions of the most prominent dual inhibitor (5j) with the enzymes. Furthermore, in silico ADME and PAMPA-blood–brain barrier (BBB) studies were conducted.

Considering the complex pathogenesis of Alzheimer’s disease (AD), the multi-target ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target strategy. Thus, one novel pyrrole-based hydrazide (vh0) and four corresponding hydrazide–hydrazones (vh1-4) were synthesized by applying highly efficient MW-assisted synthetic protocols. The synthetic pathway provided excellent yields and reduced reaction times under microwave conditions compared to conventional heating. The biological assays indicated that most of the novel pyrroles are selective MAO-B inhibitors with IC₅₀ in the nanomolar range (665 nM) and moderate AChE inhibitors. The best dual-acting MAO-B/AChE inhibitor (IC₅₀ hMAOB–0.665 μM; IC₅₀ eeAChE—4.145 μM) was the unsubstituted pyrrole-based hydrazide (vh0). Importantly, none of the novel molecules displayed hMAOA-blocking capacities. The radical-scavenging properties of the compounds were examined using DPPH and ABTS in vitro tests. Notably, the hydrazide vh0 demonstrated the best antioxidant activities. In addition, in silico simulations using molecular docking and MM/GBSA, targeting the AChE (PDB ID: 4EY6) and MAO-B (PDB: 2V5Z), were utilized to obtain active conformations and to optimize the most prominent dual inhibitor (vh0). The ADME and in vitro PAMPA studies demonstrated that vh0 could cross the blood–brain barrier, and it poses good lead-like properties. Moreover, the optimized molecular structures and the frontier molecular orbitals were examined via DFT studies at 6-311G basis set in the ground state.

The current study is focused on investigation and quantitation of seven commercially available on the Bulgarian market food supplements, containing multivitamin mixtures of water-soluble and fat-soluble vitamins. In addition, a second fermentation brewer's yeast is also analyzed. The analytical procedures are performed on a RP-HPLC/DAD using Purospher STAR C18 (Merck Millipore, Germany) 5 μm, 25 × 0.46 cm column, conditioned at 25 °C in a column oven. Dionex UltiMate 3000 high performance liquid chromatograph was carried out in diode array detector, set up at 270 nm for water-soluble vitamins, except for vitamin B₅, where 210 nm was applied as analytical wavelength. The fat-soluble vitamins were detected at 325 nm and 265 nm for vitamin A and vitamin E, respectively. Two general methods were developed where Method 1 was based on gradient elution and Method 2 was based on isocratic elution. Both methods identified stated by the manufacturer labeled amounts. The developed methods are applicable for routine analysis of vitamin contents both in multivitamin preparations and in brewer's yeast from secondary fermentation.