From ligand to complexes: inhibition of HIV-1 Integrase by beta-diketo acid metal complexes

Recently, a class of compounds bearing a β-diketo acid moiety have emerged as the most promising lead in anti-HIV-1 IN drug discovery. It is believed that the β-diketo acid pharmacophoric motif could be involved in a functional sequestration of one or both divalent metal ions, which are critical cofactors at the enzyme catalytic site. This would subsequently block the transition state of the IN-DNA complex. In this scenario, it is of paramount importance to acquire information about the mode of action of diketo acids, which could then be useful in the design of new compounds as IN inhibitors

Metal-Chelating 2‑Hydroxyphenyl Amide Pharmacophore for Inhibition of Influenza Virus Endonuclease

The influenza virus PA endonuclease is an attractive target for development of novel anti-influenza virus therapeutics. Reported PA inhibitors chelate the divalent metal ion(s) in the enzyme’s catalytic site, which is located in the Nterminal part of PA (PA-Nter). In this work, a series of 2- hydroxybenzamide-based compounds have been synthesized and biologically evaluated in order to identify the essential pharmacophoric motif, which could be involved in functional sequestration of the metal ions (probably Mg2+) in the catalytic site of PA. By using HL1, H2L2, and HL3 as model ligands with Mg2+ ions, we isolated and fully characterized a series of complexes and tested them for inhibitory activity toward PA-Nter endonuclease. H2L2 and the corresponding Mg2+ complex showed an interesting inhibition of the endonuclease activity. The crystal structures of the uncomplexed HL1 and H2L2 and of the isolated magnesium complex [Mg(L3)2(MeOH)2]·2MeOH were solved by X-ray diffraction analysis. Furthermore, the speciation models for HL1, H2L2, and HL3 with Mg2+ were obtained, and the formation constants of the complexes were measured. Preliminary docking calculations were conducted to investigate the interactions of the title compounds with essential amino acids in the PANter active site. These findings supported the “two-metal” coordination of divalent ions by a donor triad atoms chemotype as a powerful strategy to develop more potent PA endonuclease inhibitors

Supplementary data for article: Milenković, M. R.; Bacchi, A.; Cantoni, G.; Radulović, S. S.; Gligorijević, N.; Aranđelović, S.; Sladić, D.; Vujčić, M.; Mitić, D.; Anđelković, K. K. Synthesis, Characterisation and Biological Activity of Co(III) Complex with the Condensation Product of 2-(Diphenylphosphino)Benzaldehyde and Ethyl Carbazate. Inorganica Chimica Acta 2013, 395, 33–43. https://doi.org/10.1016/j.ica.2012.09.043

Supplementary material for: [https://doi.org/10.1016/j.ica.2012.09.043]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1618

Synthesis of Imidazolidin-2-ones and Imidazol-2-ones via Base-Catalyzed Intramolecular Hydroamidation of Propargylic Ureas under Ambient Conditions

The first organo-catalyzed synthesis of imidazolidin-2-ones and imidazol-2-ones via intramolecular hydroamidation of propargylic ureas is reported. The phosphazene base BEMP turned out to be the most active organo-catalyst compared with guanidine and amidine bases. Excellent chemo- and regioselectivities to five-membered cyclic ureas have been achieved under ambient conditions, with a wide substrate scope and exceptionally short reaction times (down to 1 min). A base-mediated isomerization step to an allenamide intermediate is the most feasible reaction pathway to give imidazol-2-ones, as suggested by DFT studies

Chemometric-assisted cocrystallization: Supervised pattern recognition for predicting the formation of new functional cocrystals

Owing to the antimicrobial and insecticide properties, the use of natural compounds like essential oils and their active components has proven to be an effective alternative to synthetic chemicals in different fields ranging from drug delivery to agriculture and from nutrition to food preservation. Their limited application due to the high volatility and scarce water solubility can be expanded by using crystal engineering approaches to tune some properties of the active molecule by combining it with a suitable partner molecule (coformer). However, the selection of coformers and the experimental effort required for discovering cocrystals are the bottleneck of cocrystal engineering. This study explores the use of chemometrics to aid the discovery of cocrystals of active ingredients suitable for various applications. Partial Least Squares–Discriminant Analysis is used to discern cocrystals from binary mixtures based on the molecular features of the coformers. For the first time, by including failed cocrystallization data and considering a variety of chemically diverse compounds, the proposed method resulted in a successful prediction rate of 85% for the test set in the model validation phase and of 74% for the external test set

Electronic Supplementary Information (ESI) for: "The interplay between spin states, geometries and biological activity of Fe(III) and Mn(II) complexes with thiosemicarbazone"

Fe(III) and Mn(II) complexes with condensation product of thiosemicarbazide and 2-acetylthiazole (HL1, (E)-2-(1-(thiazol-2-yl)ethylidene)hydrazine-1-carbothioamide) have been synthesized and characterized by single-crystal X-ray diffraction, IR spectroscopy, and elemental analysis. In both complexes, the thiosemicarbazone ligand is coordinated in deprotonated form through the NNS donor set of atoms. However, while Fe(III) complex is in the doublet ground state with distorted octahedral geometry, the coordination environment around Mn(II) is distorted trigonal-prismatic, and the sextet state is found to be the ground state. DFT calculations were performed to rationalize spin state preferences, and continuous shape measure describes the deviation from ideal six-coordinated polyhedral geometries in the ground and excited states. Antimicrobial activity (against a panel of Gram-negative and Gram-positive bacteria, two yeast, and one fungal strain), brine shrimp assay, and DPPH radical scavenging activity of both complexes were evaluated, and these results relate to the electronic structure of the complexes.Additional crystallographic and computational results, and the Cartesian coordinates of all DFT optimized structuresSupplementary information for: Stojičkov, M., Zlatar, M., Mazzeo, P. P., Bacchi, A., Radanović, D., Stevanović, N., Jevtović, M., Novaković, I., Anđelković, K., Sladić, D., Čobeljić, B., Gruden, M. (2023). The interplay between spin states, geometries and biological activity of Fe(III) and Mn(II) complexes with thiosemicarbazone. Polyhedron, 237, 116389. [https://doi.org/10.1016/j.poly.2023.116389]Published version of the manuscript: [https://cer.ihtm.bg.ac.rs/handle/123456789/6041]Accepted version of the manuscript: [https://cer.ihtm.bg.ac.rs/handle/123456789/6042

Supplementary data for article: Milenković, M. R.; Bacchi, A.; Cantoni, G.; Vilipić, J.; Sladić, D.; Vujčić, M.; Gligorijević, N.; Jovanovic, K.; Radulović, S. S. Synthesis, Characterization and Biological Activity of Three Square-Planar Complexes of Ni(II) with Ethyl (2E)-2-[2-(Diphenylphosphino) Benzylidene]Hydrazinecarboxylate and Monodentate Pseudohalides. European Journal of Medicinal Chemistry 2013, 68, 111–120. https://doi.org/10.1016/j.ejmech.2013.07.039

Supplementary material for: [https://doi.org/10.1016/j.ejmech.2013.07.039]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1436