No abstract

Among many others, coumarin derivatives are known to show human carbonic anhydrase (hCA) inhibitory activity. Since hCA inhibition is one of the underlying mechanisms that account for the activities of some antiepileptic drugs (AEDs), hCA inhibitors are expected to have antiseizure properties. There are also several studies reporting compounds with an imidazole and/or benzimidazole moiety which exert these pharmacological properties. In this study, we prepared fifteen novel coumarin-bearing imidazolium and benzimidazolium chloride, nine novel benzoxazinone-bearing imidazolium and benzimidazolium chloride derivatives and evaluated their hCA inhibitory activities and along with fourteen previously synthesized derivatives we scanned their anticonvulsant effects. As all compounds inhibited purified hCA isoforms I and II, some of them also proved protective against Maximal electroshock seizure (MES) and ScMet induced seizures in mice. Molecular docking studies with selected coumarin derivatives have revealed that these compounds bind to the active pocket of the enzyme in a similar fashion to that previously described for coumarin derivatives.

Background: The MAO enzyme which is presented in the brain and peripheral tissues and is a significant enzyme that is responsible for the deamination of biogenic amines and thus regulation of neurotransmitter levels. The reaction of these neurotransmitters with MAO enzyme produces aldehyde and free amine. MAO enzyme consists of two isoforms, MAO-A and MAO-B, which are characterized by amino acid sequence, three-dimensional structure, substrate preference and inhibitor selectivity. Dopamine, tyramine, and tryptamine are substrates of both MAO isoforms and MAO inhibitors such as clorgiline, selegiline that are used as medications in neurodegenerative and neurological diseases. In particular, MAO-A inhibitors are used in the treatment of depression, while MAO-B inhibitors are used in the treatment of Parkinson's disease. It is also investigated whether MAO-B inhibitors are effective in the treatment of Alzheimer's disease. Nowadays, life expectancy has increased; as a result, neurodegenerative diseases such as Parkinson's and Alzheimer's disease have started to seen more frequently. The elderly population is increasing day by day. As a result of these common diseases in the elderly people, these people are unable to do their jobs and need care. Therefore, these diseases have become a significant health problem in society. Methods: In this study, review, inclusion and exclusion criteria were used. Research articles with peer-reviewed were searched. The quality of the examined articles was evaluated with standard tools. The information obtained was analyzed conceptually by using qualitative content analysis methodology. Results: One hundred and five papers were included in the review. The current MAO-B inhibitors and their usage areas are discussed together with the structures of the drugs; also, their possible effects in Alzheimer’s and Parkinson’s treatment are evaluated. In addition, different articles have been compiled in which structures such as arylalkylamines, chalcones, benzoquinone, benzoxazinone, chromen are substituted with various functional groups and aromatic rings, and structures of 44 different compounds that have recently been developed and their inhibitory effects on MAO-B enzyme. As a result, the structure required for MAO-B inhibition and SAR studies are discussed and the literature was shed light. Conclusion: Many studies demonstrate that MAO-B activity increases with age in brain tissue, cerebrospinal fluid (CSF), and platelets in Alzheimer's patients. This suggests that MAO-B inhibitor drugs, which may be effective in the treatment of Parkinson's disease, may also be effective in the treatment of Alzheimer's disease. This article was written to explain the multifaceted MAO-B inhibitor molecules.

Aims Flavonoids and related compounds, such as quercetin‐based antiviral drug Gene‐Eden‐VIR/Novirin, inhibit the protease of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The alkylated chalcones isolated from Angelica keiskei inhibit SARS‐CoV proteases. In this study, we aimed to compare the anti‐SARS CoV‐2 activities of both newly synthesized chalcone derivatives and these two drugs. Methods Determination of the potent antiviral activity of newly synthesized chalcone derivatives against SARS‐CoV‐2 by calculating the RT‐PCR cycling threshold ( C t ) values. Results Antiviral activities of the compounds varied because of being dose dependent. Compound 6 , 7 , 9 , and 16 were highly effective against SARS‐CoV‐2 at the concentration of 1.60 µg/mL. Structure‐based virtual screening was carried out against the most important druggable SARS‐CoV‐2 targets, viral RNA‐dependent RNA polymerase, to identify putative inhibitors that could facilitate the development of potential anti‐coronavirus disease‐2019 drug candidates. Conclusions Computational analyses identified eight compounds inhibiting each target, with binding affinity scores ranging from −4.370 to −2.748 kcal/mol along with their toxicological, ADME, and drug‐like properties.

In an attempt to develop potent and selective anticancer agents, some 5‐ or 6‐ and N‐substituted benzoxazol‐2‐carboxamide derivatives were designed, synthesized, and evaluated for their cyclooxygenase inhibitory, antioxidant, and anti‐proliferative activity against MCF‐7 and MDA‐MB‐231 cell lines. Among them 5‐OMe, N‐piperidine substituted (compound 30), 5‐OMe, N‐4‐methylpiperidine substituted (compound 31) and 5‐Cl, N‐piperidine substituted (compound 34) benzoxazole 2‐carboxamide compounds have a moderate inhibitory effect in COX‐1 and COX‐2 enzymes. Anti‐proliferative studies show that compound 30 (IC50=5.35 μM) and compound 31 (IC50=5.82 μM) have similar activity to reference drug 5‐FU (IC50=3.95 μM) on MCF‐7 cell but they have lower toxic effect for healthy WI‐38 cell line. For the MCF‐7 cell line, compounds 30 and 31 show approximately 1.5 times higher selectivity compared to the 5‐FU control. Among the synthesized compounds 30, 31, and 34 had the best anti‐proliferative effect and were used to perform flow cytometry and cell cycle analysis on MCF‐7 cell line. To predict the binding modes and pharmacokinetic parameters of all compounds, in silico studies were carried out. These compounds may shed light on cancer treatment and cancer research.