DFT study of the radical scavenging activity of isoxanthohumol, humulones (α-acids), and iso-α-acids from beer

Humulones and iso-humulones are potent natural antioxidants found in beer. In this study, density functional theory (DFT) method was applied for elucidating the structure-antioxidant activity relationship and molecular mechanism of antioxidant activity of eight bioactive humulones previously identified in different beer samples: isoxanthohumol, (R)- and (S)-adhumulone, cis- and trans-iso-adhumulone, cis- and trans-iso-n-humulone, and desdimethyl-octahydro-iso-cohumulone. The calculated bond dissociation enthalpies (BDEs) suggest that desdimethyl-octahydro-iso-cohumulone was the most potent compound with BDEs 5.1 and 23.9 kJ/mol lower compared to the values for resveratrol in gas phase and water, respectively. The enolic –OH is the most reactive site for hydrogen atom transfer (HAT). The presence of β-keto group with respect to enolic –OH diminishes the HAT potency via the formation of a strong intramolecular hydrogen bond. Another common antioxidant mechanism, single electron transfer followed by proton transfer (SET-PT), is only feasible for isoxanthohumol. The results of this study indicate a strong correlation between the increased antioxidant activity of beer products and the higher content of reduced iso-α-acids

Supplementary data for the article: Glišić, B. Đ.; Nikodinovic-Runic, J.; Ilic-Tomic, T.; Wadepohl, H.; Veselinović, A.; Opsenica, I. M.; Djuran, M. I. Synthesis, Cytotoxic Activity and DNA-Binding Properties of Copper(II) Complexes with Terpyridine. Polyhedron 2018, 139, 313–322. https://doi.org/10.1016/j.poly.2017.11.008

Supplementary material for: [https://doi.org/10.1016/j.poly.2017.11.008]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2581

Tetraoxanes induced ROS production and activation of caspase 3 in HeLa cells

It was demonstrated that mixed steroidal tetraoxanes inhibit cancer cell proliferation at micromolar level through an apoptotic mechanism. It will be interesting to see if these compounds may possibly induce oxidative stress, which could lead to induction of apoptosis in tumour cells. As tumour cells contain more iron than other normal tissues it is reasonable to suggest that tetraoxanes could react with iron, generating alkoxy radicals or even highly reactive hydroxyl radicals in a Fenton-like reaction. To gain further insight into the mechanism of cell death induced by tetraoxane endoperoxides, we tested production of reactive oxygen species (ROS) and level of activation of caspase 3 in tumour cells treated with several newly synthesized tetraoxanes

Supplementary data for the article: Andrejević, T. P.; Nikolić, A. M.; Glišić, B. Đ.; Wadepohl, H.; Vojnovic, S.; Zlatović, M.; Petković, M.; Nikodinovic-Runic, J.; Opsenica, I. M.; Djuran, M. I. Synthesis, Structural Characterization and Antimicrobial Activity of Silver(I) Complexes with 1-Benzyl-1H-Tetrazoles. Polyhedron 2018, 154, 325–333. https://doi.org/10.1016/j.poly.2018.08.001

Supplementary data for: [https://doi.org/10.1016/j.poly.2018.08.001]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc2046ft&sid=DataCite]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc2046gv&sid=DataCite]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2228]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/2991

Supplementary material for the article: Savić, N. D.; Vojnovic, S.; Glišić, B. Đ.; Crochet, A.; Pavic, A.; Janjić, G. V.; Pekmezović, M.; Opsenica, I. M.; Fromm, K. M.; Nikodinovic-Runic, J.; et al. Mononuclear Silver(I) Complexes with 1,7-Phenanthroline as Potent Inhibitors of Candida Growth. Eur. J. Med. Chem. 2018, 156, 760–773. https://doi.org/10.1016/j.ejmech.2018.07.049

Supplementary data for: [https://doi.org/10.1016/j.ejmech.2018.07.049]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc1zdr7c&sid=DataCite]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc1zdr6b&sid=DataCite]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc1zdr59&sid=DataCite]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2213]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/2993

Supplementary data for the article: Glišić, B. Đ.; Nikodinovic-Runic, J.; Ilic-Tomic, T.; Wadepohl, H.; Veselinović, A.; Opsenica, I. M.; Djuran, M. I. Synthesis, Cytotoxic Activity and DNA-Binding Properties of Copper(II) Complexes with Terpyridine. Polyhedron 2018, 139, 313–322. https://doi.org/10.1016/j.poly.2017.11.008

Supplementary material for: [https://doi.org/10.1016/j.poly.2017.11.008]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2581

Supplementary data for the article: Andrejević, T. P.; Nikolić, A. M.; Glišić, B. Đ.; Wadepohl, H.; Vojnovic, S.; Zlatović, M.; Petković, M.; Nikodinovic-Runic, J.; Opsenica, I. M.; Djuran, M. I. Synthesis, Structural Characterization and Antimicrobial Activity of Silver(I) Complexes with 1-Benzyl-1H-Tetrazoles. Polyhedron 2018, 154, 325–333. https://doi.org/10.1016/j.poly.2018.08.001

Supplementary data for: [https://doi.org/10.1016/j.poly.2018.08.001]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc2046ft&sid=DataCite]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc2046gv&sid=DataCite]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2228]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/2991

Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria

Significantly more potent second generation 4-amino-7-chloroquinoline (4,7-ACQ) based inhibitors of the botulinum neurotoxin serotype A (BoNT/A) light chain were synthesized. Introducing an amino group at the C(3) position of the cholate component markedly increased potency (IC50 values for such derivatives ranged from 0.81 to 2.27 mu M). Two additional subclasses were prepared: bis(steroidal)-4,7-ACQ derivatives and bis(4,7-ACQ)cholate derivatives; both classes provided inhibitors with nanomolar-range potencies (e.g., the K-i of compound 67 is 0.10 mu M). During BoNT/A challenge using primary neurons, select derivatives protected SNAP-25 by up to 89%. Docking simulations were performed to rationalize the compounds' in vitro potencies. In addition to specific residue contacts, coordination of the enzyme's catalytic zinc and expulsion of the enzyme's catalytic water were a consistent theme. With respect to antimalarial activity, the compounds provided better IC90 activities against chloroquine resistant (CQR) malaria than CQ, and seven compounds were more active than mefloquine against CQR strain W2

Supplementary material for the article: Savić, N. D.; Vojnovic, S.; Glišić, B. Đ.; Crochet, A.; Pavic, A.; Janjić, G. V.; Pekmezović, M.; Opsenica, I. M.; Fromm, K. M.; Nikodinovic-Runic, J.; et al. Mononuclear Silver(I) Complexes with 1,7-Phenanthroline as Potent Inhibitors of Candida Growth. Eur. J. Med. Chem. 2018, 156, 760–773. https://doi.org/10.1016/j.ejmech.2018.07.049

Supplementary data for: [https://doi.org/10.1016/j.ejmech.2018.07.049]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc1zdr7c&sid=DataCite]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc1zdr6b&sid=DataCite]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc1zdr59&sid=DataCite]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2213]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/2993

Mononuclear silver(I) complexes with 1,7-phenanthroline as potent inhibitors of Candida growth

Mononuclear silver(I) complexes with 1,7-phenanthroline (1,7-phen), [Ag(NO3-O,O′) (1,7-phen-N7)2] (1) and [Ag(1,7-phen-N7)2]X, X = ClO4− (2), CF3SO3− (3), BF4− (4) and SbF6− (5) were synthesized and structurally characterized by NMR (1H and 13C), IR and UV–Vis spectroscopy and ESI mass spectrometry. The crystal structures of 1, 3 and 4 were determined by single-crystal X-ray diffraction analysis. In all these complexes, 1,7-phen coordinates to the Ag(I) ion in a monodentate fashion via the less sterically hindered N7 nitrogen atom. The investigation of the solution stability of 1–5 in DMSO revealed that they are sufficiently stable in this solvent at room temperature. Complexes 1–5 showed selectivity towards Candida spp. in comparison to bacteria, effectively inhibiting the growth of four different Candida species with minimal inhibitory concentrations (MIC) between 1.2 and 11.3 μM. Based on the lowest MIC values and the lowest cytotoxicity against healthy human fibroblasts with selectivity index of more than 30, the antifungal potential was examined in detail for the complex 1. It had the ability to attenuate C. albicans virulence and to reduce epithelial cell damage in the cell infection model. Induction of reactive oxygen species (ROS) response has been detected in C. albicans, with fungal DNA being one of the possible target biomolecules. The toxicity profile of 1 in the zebrafish model (Danio rerio) revealed improved safety and activity in comparison to that of clinically utilized silver(I) sulfadiazine