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Anabaenopeptins are common metabolites of cyanobacteria. In the course of reisolation of the known aeruginosins KT608A and KT608B for bioassay studies, we noticed the presence of some unknown anabaenopeptins in the extract of a Microcystis cell mass collected during the 2016 spring bloom event in Lake Kinneret, Israel. The 1H NMR spectra of some of these compounds presented a significant difference in the appearance of the ureido bridge protons, and their molecular masses did not match any one of the 152 known anabaenopeptins. Analyses of the 1D and 2D NMR, HRMS, and MS/MS spectra of the new compounds revealed their structures as the hydantoin derivatives of anabaenopeptins A, B, F, and 1[Dht]-anabaenopeptin A and oscillamide Y (1, 2, 3, 6, and 4, respectively) and a new anabaenopeptin, 1[Dht]-anabaenopeptin A (5). The known anabaenopeptins A, B, and F and oscillamide Y (7, 8, 9, and 10, respectively) were present in the extract as well. We propose that 1–4 and 6 are the possible missing intermediates in the previously proposed partial biosynthesis route to the anabaenopeptins. Compounds 1–6 were tested for inhibition of the serine proteases trypsin and chymotrypsin and found inactive at a final concentration of ca. 54 μM. [ABSTRACT FROM AUTHOR]

Hydantoin derivatives are commonly used anticonvulsants. In general, they are effective for partialonset seizures and tonic-clonic seizures, but not for absence seizures. Phenytoin is the most important drug in this group, and other drugs, ethotoin, and mephenytoin, are also commonly used to treat epilepsy. Prodrugs such as derivatives have been created. Phenytoin is effective in some cases of trigeminal neuralgia and related neuralgia. Phenytoin is also used to treat arrhythmias. Hydantoins or glycolylureas are heterocyclic organic compounds with the formula CH2C(O)NHC(O)NH. It is a colorless solid formed by the reaction of glycolic acid and urea. It is an oxidized derivative of imidazolidine. In a more general sense, hydantoins can refer to groups and classes of compounds that share the same ring structure as their parent. For example, phenytoin (see below) has two phenyl groups substituted at the 5th carbon of the hydantoin molecule. Actual chemotherapy for epilepsy dates back to the 1850s when "inorganic bromides" were introduced. However, it is worth noting that around the 1920s, the therapeutic and beneficial use of 'phenobarbital' usheredin an era of meaningful treatment of epilepsy. Hydantoin ring chemistry is the synthesis of rings by various methods and their applications in the medical field. Previous descriptions of hydantoin-containing compounds have broad pharmacological and biological activities, including anticancer, anti-inflammatory, anti-immune, antimetabolite, antioxidant, antibacterial, CNS-related, anticonvulsant, antitussive, and cytoprotective activities. [ABSTRACT FROM AUTHOR]

Anabaenopeptins are common metabolites of cyanobacteria. In the course of reisolation of the known aeruginosins KT608A and KT608B for bioassay studies, we noticed the presence of some unknown anabaenopeptins in the extract of a Microcystis cell mass collected during the 2016 spring bloom event in Lake Kinneret, Israel. The 1H NMR spectra of some of these compounds presented a significant difference in the appearance of the ureido bridge protons, and their molecular masses did not match any one of the 152 known anabaenopeptins. Analyses of the 1D and 2D NMR, HRMS, and MS/MS spectra of the new compounds revealed their structures as the hydantoin derivatives of anabaenopeptins A, B, F, and 1[Dht]-anabaenopeptin A and oscillamide Y (1, 2, 3, 6, and 4, respectively) and a new anabaenopeptin, 1[Dht]-anabaenopeptin A (5). The known anabaenopeptins A, B, and F and oscillamide Y (7, 8, 9, and 10, respectively) were present in the extract as well. We propose that 1–4 and 6 are the possible missing intermediates in the previously proposed partial biosynthesis route to the anabaenopeptins. Compounds 1–6 were tested for inhibition of the serine proteases trypsin and chymotrypsin and found inactive at a final concentration of ca. 54 μM.

This study aimed to assess two novel 5-arylideneimidazolidine-2,4-dione (hydantoin) derivatives (JH3 and JH10) demonstrating photoprotective activity using the reconstructed human skin model EpiskinTM. The skin permeability, irritation, and phototoxicity of the compounds was evaluated in vitro. Moreover, the in vitro genotoxicity and human metabolism of both compounds was studied. For skin permeation and irritation experiments, the test compounds were incorporated into a formulation. It was shown that JH3 and JH10 display no skin irritation and no phototoxicity. Both compounds did not markedly enhance the frequency of micronuclei in CHO-K1 cells in the micronucleus assay. Preliminary in vitro studies with liver microsomes demonstrated that hydrolysis appears to constitute their important metabolic pathway. EpiskinTM permeability experiments showed that JH3 permeability was lower than or close to currently used UV filters, whereas JH10 had the potential to permeate the skin. Therefore, a restriction of this compound permeability should be obtained by choosing the right vehicle or by optimizing it, which should be addressed in future studies. [ABSTRACT FROM AUTHOR]

[Display omitted] • Six new hydantoins derivatives were designed, synthesized and evaluated for their in vitro antiplasmodial activity. • The most active compound 2c showed excellent inhibitory activity on the tested plasmodium 3D7 strain with an IC 50 value of 3.97 ± 0.01 nM, which was three-fold better than that of chloroquine. • Substitution with a different R group at the N -5 position of the hydantoin scaffold resulted in a marked decrease in antimalarial potency. • All hydantoins derivatives tested were inactive against human MCR-5 normal cells with IC 50 values exceeding 100 μM. Malaria, a devastating disease, has claimed numerous lives and caused considerable suffering, with young children and pregnant women being the most severely affected group. However, the emergence of multidrug-resistant strains of Plasmodium and the adverse side effects associated with existing antimalarial drugs underscore the urgent need for the development of novel, well-tolerated, and more efficient drugs to combat this global health threat. To address these challenges, six new hydantoins derivatives were synthesized and evaluated for their in vitro antiplasmodial activity. Notably, compound 2c exhibited excellent inhibitory activity against the tested Pf 3D7 strain, with an IC 50 value of 3.97 ± 0.01 nM, three-fold better than chloroquine. Following closely, compound 3b demonstrated an IC 50 value of 27.52 ± 3.37 µM against the Pf 3D7 strain in vitro. Additionally, all the hydantoins derivatives tested showed inactive against human MCR-5 cells, with an IC 50 value exceeding 100 μM. In summary, the hydantoin derivative 2c emerges as a promising candidate for further exploration as an antiplasmodial compound. [ABSTRACT FROM AUTHOR]

This study aimed to assess two novel 5-arylideneimidazolidine-2,4-dione (hydantoin) derivatives (JH3 and JH10) demonstrating photoprotective activity using the reconstructed human skin model EpiskinTM. The skin permeability, irritation, and phototoxicity of the compounds was evaluated in vitro. Moreover, the in vitro genotoxicity and human metabolism of both compounds was studied. For skin permeation and irritation experiments, the test compounds were incorporated into a formulation. It was shown that JH3 and JH10 display no skin irritation and no phototoxicity. Both compounds did not markedly enhance the frequency of micronuclei in CHO-K1 cells in the micronucleus assay. Preliminary in vitro studies with liver microsomes demonstrated that hydrolysis appears to constitute their important metabolic pathway. EpiskinTM permeability experiments showed that JH3 permeability was lower than or close to currently used UV filters, whereas JH10 had the potential to permeate the skin. Therefore, a restriction of this compound permeability should be obtained by choosing the right vehicle or by optimizing it, which should be addressed in future studies.