Hydantoins, a class of five-membered heterocyclic compounds, exhibit diverse biological activities. The aim of this study was to synthesize and characterize a series of novel 3,5-disubstituted hydantoins and to investigate their antiproliferative activity against human cancer cell lines. The new hydantoin derivatives - were prepared as racemic mixtures of - and -isomers via a base-assisted intramolecular amidolysis of C-3 functionalized β-lactams.
View Article and Find Full Text PDFThe total synthesis of two new marine natural products, (±)-marinoaziridine B and (±)--methyl marinoaziridine A , was accomplished. The (±)-marinoaziridine was prepared in a six-step linear sequence with a 2% overall yield. The key steps in our strategy were the preparation of the chiral epoxide (±)- using the Johnson Corey Chaykovsky reaction, followed by the ring-opening reaction and the Staudinger reaction.
View Article and Find Full Text PDFA diastereomeric mixture of racemic 3-phthalimido--lactam / was synthesized by the Staudinger reaction of carboxylic acid activated with 2-chloro-1-methylpyridinium iodide and imine . The amino group at the C3 position of the -lactam ring was used for further structural upgrade. --lactam ureas were prepared by the condensation reaction of the amino group of -lactam ring with various aromatic and aliphatic isocyanates.
View Article and Find Full Text PDFSets of 346 herbicides in use and 163 no longer in use were collected from open access online sources and compared in silico with cholinesterases inhibitors (ChI) and drugs in terms of physicochemical profile and estimated toxic effects on human health. The screening revealed at least one potential adverse consequence for each herbicide class assigned according to their mode of action on weeds. The classes with most toxic warnings were K1, K3/N, F1 and E.
View Article and Find Full Text PDFCancer is one of the leading causes of death worldwide, with nearly 10 million deaths in 2020 [...
View Article and Find Full Text PDFFerroptosis is a regular cell death pathway that has been proposed as a suitable therapeutic target in cancer and neurodegenerative diseases. Since its definition in 2012, a few hundred ferroptosis modulators have been reported. Based on a literature search, we collected a set of diverse ferroptosis modulators and analyzed them in terms of their structural features and physicochemical and drug-likeness properties.
View Article and Find Full Text PDFTen different fluorinated aromatic epoxides have been tested as potential substrates for halohydrin dehalogenase (HHDH) HheC. The majority of investigated epoxides are useful building blocks in synthetic chemistry applications, with a number of them being polysubstituted. Moderate to high enantioselectivities ( = 15 → 200) were observed in azidolysis, allowing the synthesis of enantioenriched ()-azido alcohols containing fluorine in the molecule.
View Article and Find Full Text PDFInvited for the cover of this issue are Zlatko Brkljača, Maja Majerić Elenkov and co-workers at the Ruđer Bošković Institute and University of Zagreb. The image depicts the enzyme halohydrin dehalogenase HheC, which is made up of four identical subunits, with marked catalytic residues and volumetric maps of water and DMSO in the active site. Read the full text of the article at 10.
View Article and Find Full Text PDFAlthough the application of organic solvents in biocatalysis is well explored, in-depth understanding of the interactions of solvent with proteins, in particular oligomeric ones, is still scant. Understanding these interactions is essential in tailoring enzymes for industrially relevant catalysis in nonaqueous media. In our study, the homotetrameric enzyme halohydrin dehalogenase (HHDH) from Agrobacterium radiobacter AD1 (HheC) was investigated, as a model system, in DMSO/water solvent mixtures.
View Article and Find Full Text PDFCompounds from the plant world that possess antioxidant abilities are of special importance for the food and pharmaceutical industry. Coumarins are a large, widely distributed group of natural compounds, usually found in plants, often with good antioxidant capacity. The coumarin-hydroxybenzohydrazide derivatives were synthesized using a green, one-pot protocol.
View Article and Find Full Text PDFWidespread use of herbicides results in the global increase in weed resistance. The rotational use of herbicides according to their modes of action (MoAs) and discovery of novel phytotoxic molecules are the two strategies used against the weed resistance. Herein, Random Forest modeling was used to build predictive models and establish comprehensive characterization of structure-activity relationships underlying herbicide classifications according to their MoAs and weed selectivity.
View Article and Find Full Text PDFOxidative stress is defined as a disturbance in the prooxidant/antioxidant balance in favor of the former and a loss of control over redox signaling processes, leading to potential biomolecular damage. It is involved in the etiology of many diseases, varying from diabetes to neurodegenerative diseases and cancer. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor and reported as one of the most important oxidative stress regulators.
View Article and Find Full Text PDFA year after the initial outbreak, the COVID-19 pandemic caused by SARS-CoV-2 virus remains a serious threat to global health, while current treatment options are insufficient to bring major improvements. The aim of this study is to identify repurposable drug candidates with a potential to reverse transcriptomic alterations in the host cells infected by SARS-CoV-2. We have developed a rational computational pipeline to filter publicly available transcriptomic datasets of SARS-CoV-2-infected biosamples based on their responsiveness to the virus, to generate a list of relevant differentially expressed genes, and to identify drug candidates for repurposing using LINCS connectivity map.
View Article and Find Full Text PDFAntioxidants (Basel)
July 2020
Oxidative stress is represented as an imbalance between reactive oxygen species (ROS) production and the response of antioxidant proteins [...
View Article and Find Full Text PDFThe vast majority of previous studies dealing with antioxidant potency of (poly)phenols does not investigate the fate of phenoxyl radical obtained after single free radical scavenging. We investigated possible pathways of inactivation of ferulic acid phenoxyl radical (FAPR) using DFT method. Direct coupling with a set of 10 physiologically important free radicals, H-atom donation and dimerization were analysed by estimation of Gibbs free energy changes related to these processes.
View Article and Find Full Text PDFTwo series of 6-(1,2,3-triazolyl)-2,3-dibenzyl-l-ascorbic acid derivatives with the hydroxyethylene (8a-8u) and ethylidene linkers (10c-10p) were synthesized and evaluated for their antiproliferative activity against seven malignant tumor cell lines and antiviral activity against a broad range of viruses. Conformationally unrestricted spacer between the lactone and 1,2,3-triazole units in 8a-8u series had a profound effect on antitumor activity. Besides, the introduction of a long side chain at C-4 of 1,2,3-triazole that led to the synthesis of decyl-substituted 2,3-dibenzyl-l-ascorbic acid 8m accounted for a selective and potent antiproliferative activity on breast cancer MCF-7 cells cells in the nM range.
View Article and Find Full Text PDFThe novel 4-substituted 1,2,3-triazole L-ascorbic acid (L-ASA) conjugates with hydroxyethylene spacer as well as their conformationally restricted 4,5-unsaturated analogues were synthesized as potential antioxidant and antiproliferative agents. An evaluation of the antioxidant activity of novel compounds showed that the majority of the 4,5-unsaturated L-ASA derivatives showed a better antioxidant activity compared to their saturated counterparts. -Hydroxyphenyl (), -pentylphenyl () and 2-hydroxyethyl () substituted 4,5-unsaturated 1,2,3-triazole L-ASA derivatives exhibited very efficient and rapid (within 5 min) 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (, : IC = 0.
View Article and Find Full Text PDFChalcones are polyphenolic secondary metabolites of plants, many of which have antioxidant activity. Herein, a set of 26 synthetic chalcone derivatives with alkyl substituted pyrazine heterocycle A and four types of the monophenolic ring B, were evaluated for the potential radical scavenging and antioxidant cellular capacity influencing the growth of cells exposed to H₂O₂. Before that, compounds were screened for cytotoxicity on THP-1 and HepG2 cell lines.
View Article and Find Full Text PDFPleiotropic effects of curcumin have been the subject of intensive research. The interest in this molecule for preventive medicine may further increase because of its potential to modulate inflamm-aging. Although direct data related to its effect on inflamm-aging does not exist, there is a strong possibility that its well-known anti-inflammatory properties may be relevant to this phenomenon.
View Article and Find Full Text PDFQuercetin (Q) is a natural polyphenol with high radical scavenging capacity, but low in vivo bioavailability. It is extensively transformed by host phase II metabolism and microbiota. Herein, effects of major in vitro and in vivo conjugation transformations of Q on its radical scavenging capacity and human serum albumin (HSA) binding were studied by using appropriate computational approaches, DFT (U)B3LYP/6-31 + G(d,p) and molecular docking, respectively.
View Article and Find Full Text PDFThe Croatian Chemical Society was established in 1926 and has developed over the decades into a society that actively supports all chemical activities in Croatia. The Society has eight divisions, the youngest of which, the Division of Medicinal and Pharmaceutical Chemistry, was established in 2012 and immediately became a member of the European Federation of Medicinal Chemistry (EFMC). The mission of the Medicinal and Pharmaceutical Chemistry Division is the promotion and development of scientific, professional, and educational activities within the medicinal chemistry community in Croatia, as well as to build partnerships and collaborations with other primarily EU-based medicinal chemistry societies.
View Article and Find Full Text PDFReaction energetics of the double (2H/2e), i.e., the first 1H/1e (catechol→ phenoxyl radical) and the second 1H/1e (phenoxyl radical→ quinone) free radical scavenging mechanisms of quercetin and its six colonic catecholic metabolites (caffeic acid, hydrocaffeic acid, homoprotocatechuic acid, protocatechuic acid, 4-methylcatechol, and catechol) were computationally studied using density functional theory, with the aim to estimate the antiradical potency of these molecules.
View Article and Find Full Text PDFThe 4-substituted 1,2,3-triazole core in designed coumarin hybrids (4-35) with diverse physicochemical properties was introduced by eco-friendly copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition under microwave irradiation. Coumarin-1,2,3-triazole-benzofused heterocycle hybrids emerged as the class of compounds exhibiting the highest antiproliferative activity. The strong relationship between lipophilicity and antiproliferative activities was observed indicating that lipophilic 1,2,3-triazole-coumarin hybrids containing phenylethyl (13), 3,5-difluorophenyl (14), 5-iodoindole (30) and benzimidazole (33 and 35) subunits showed the most potent cytostatic effects.
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