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The article compares the experimental Fourier transform-infrared, Ultraviolet-visible (UV-vis), and proton nuclear magnetic resonance (1H NMR) spectra of voriconazole and fluconazole with the density functional theory (DFT) calculations using five different functionals. The results were compared with previously reported data related to its analogue – posaconazole. The analysis of calculated infrared (IR) spectra with the use of PBE1PBE (voriconazole) or APF (fluconazole) functionals shows good accordance with the experimental IR spectrum. The best compatibility between the experimental and theoretical UV spectra was observed with the use of PBE1PBE or B3LYP functionals for voriconazole or fluconazole, respectively. The reason for the difference in the UV-vis spectra of voriconazole and fluconazole was discussed based on linear response time-dependent DFT and natural bond orbital methods. The calculated 1H NMR spectrum shows that the DFT formalism, particularly the M06L or B3LYP functionals, gives an accurate description of the voriconazole and fluconazole chemical shifts.

The presented studies aimed to evaluate the peripheral coordinating properties of a novel porphyrinoid family representative preceded by its synthesis for potential sensing purposes. Two synthetic pathways were employed to a obtain maleonitrile derivative, further used as a starting material in the cyclotetramerization reaction. In the first one, DAMN was used in sequential double-reductive alkylation with 2-thiophene-carboxyaldehyde and sodium borohydride. In the second, DAMN was used in a one-pot reaction with 2-thiophene-carboxyaldehyde in the presence of a 5-ethyl-2-methylpyridine borane complex in methanol and acetic acid. Following the Linstead approach, the cyclization reaction led to a novel symmetrical magnesium(II) octaaminoporphyrazine with methyl(2-thiophenylmethylene) substituents. The macrocycle's electrochemical properties were assessed by cyclic and differential pulse voltammetries revealing one reduction and two oxidation peak potentials. The additional spectroelectrochemical measurements showed formation of a cationic form of the macrocycle at an applied potential of 0.6 V. The coordinating properties due to the palladium ion of novel porphyrazines were measured with the use of titration combined with UV–vis spectrometry. The titration of Pd2+ revealed the good sensing activity of porphyrazine in the range of 0.1 to 5 palladium molar equivalents. In addition, Pd2+ ions coordination was also assessed by electrochemical studies, indicating the peak potential shift of 0.1 V in the presence of metal cations. DFT calculations showed the good agreement between theoretical and experimental data in the UV–vis and 1H NMR studies. [ABSTRACT FROM AUTHOR]

Using the density functional theory (DFT) formalism, we have investigated the properties of some arylsulphonyl indazole derivatives that we studied previously for their biological activity and susceptibility to interactions of azoles. This study includes the following physicochemical properties of these derivatives: electronegativity and polarisability (Mulliken charges, adjusted charge partitioning, and iterative-adjusted charge partitioning approaches); free energy of solvation (solvation model based on density model and M062X functional); highest occupied molecular orbital (HOMO)–lowest occupied molecular orbital (LUMO) gap together with the corresponding condensed Fukui functions, time-dependent DFT along with the UV spectra simulations using B3LYP, CAM-B3LYP, MPW1PW91, and WB97XD functionals, as well as linear response polarisable continuum model; and estimation of global chemical reactivity descriptors, particularly the chemical hardness factor. The charges on pyrrolic and pyridinic nitrogen (the latter one in the quinolone ring of compound 8, as well as condensed Fukui functions) reveal a significant role of these atoms in potential interactions of azole ligand–protein binding pocket. The lowest negative value of free energy of solvation can be attributed to carbazole 6, whereas pyrazole 7 has the least negative value of this energy. Moreover, the HOMO–LUMO gap and chemical hardness show that carbazole 6 and indole 5 exist as soft molecules, while fused pyrazole 7 has hard character.

Molecular hydrophobicity (lipophilicity), usually quantified as log "P" where "P" is the partition coefficient, is an important molecular characteristic in medicinal chemistry and drug design. The log "P" coefficient is one of the principal parameters for the estimation of lipophilicity of chemical compounds and pharmacokinetic properties. The understanding of log "P" parameter in the undergraduate medicinal chemistry course seems to be a pitfall for students. This parameter has typically been measured using experimental methods, but recently, log "P" has been determined using computational methods. The number of publications about lipophilicity predictions has gradually increased over the last 10 years, but the number of programs available for an online prediction of this important parameter remains limited. An interesting tool for calculation of log "P" coefficients is presented: the Virtual Computational Chemistry Laboratory (VCCLAB) package. The package includes the ALOGPS 2.1 program suitable for log "P" calculations. This software is accessible online and may be easily mastered by the undergraduate medicinal chemistry student. (Contains 1 table and 1 figure.)

Synthesis and biological evaluation of hybrid molecules combining naturally occurring antioxidant active structures with anti-inflammatory agents have been a strong trend in medicinal chemistry. This study focuses on modulating the structure of curcumin derivatives or their analogs with the use of non-steroidal anti-inflammatory drugs (NSAIDs). The combinations of curcumin, its keto-blocked derivatives, and monocarbonyl analogs with selected non-steroidal anti-inflammatory drugs (ibuprofen, naproxen) were obtained and characterized. The pyrazole, isoxazole, and benzylidene derivatives, as well as curcumin monocarbonyl analogs, were used as substrates in the reactions with selected NSAIDs. As a result of the esterification of curcumin-type diphenols, the corresponding mono- and diester-type hybrids were obtained and characterized. Moreover, in the present study, in order to verify the possibility of interactions of curcumin derivatives with the RNA binding domain of nucleocapsid phosphoprotein from SARS coronavirus 2 (PDB ID: 6VYO), we focused on the docking of the analytes to the binding pocket and analysis of amino acid interactions. The estimation of binding affinity seems to indicate that almost all synthesized compounds are able to interact with the amino acids within the cavity more effectively than referenced S-naproxen, and the most interacting amino acid residues were as follows: Arg88, Arg107, Tyr109, Gly116, Thr148, Arg149, and Asn153. Additionally, with the use of selected methods of computational chemistry (Molinspiration Cheminformatics and Osiris Property Explorer), the molecular parameters of the relevant molecules were calculated. [ABSTRACT FROM AUTHOR]

The paper compares the experimental FT-IR, UV-vis, and 1H NMR spectra of isoconazole and bifonazole with the density functional theory (DFT) calculations using different functionals. The results were compared with previously reported data related to their analogue, posaconazole. The analysis of calculated IR spectra with use of CAM-B3LYP (isoconazole) or B3LYP (bifonazole) functionals shows good accordance with the experimental IR spectrum. The best compatibility between the experimental and theoretical UV spectra was observed with the use of B3LYP or wB97XD functionals for isoconazole or bifonazole, respectively. The reason for the difference in the UV-vis spectra of isoconazole and bifonazole was discussed based on linear response time-dependent DFT and natural bond orbital methods. The calculated 1H NMR spectrum shows that the DFT formalism, particularly the B3LYP functional, give an accurate description of the isoconazole and bifonazole chemical shifts. [ABSTRACT FROM AUTHOR]

The article presents the Virtual Computational Chemistry Laboratory (VCCLAB) package, a tool that can be used to calculate log P coefficients in medicinal chemistry and drug design. It describes the key features and advantages offered by the package which includes the ALOGPS 2.1 program suitable for log P calculations. It discusses the availability of the software online, and shows that it can easily be mastered by the undergraduate medicinal chemistry student.

Nrf2 and NF-κB play a key role in inflammation-driven cancers. Conjugation of anti-inflammatory drugs with oleanolic acid oxime (OAO) may enhance their therapeutic potential as a result of downregulation of these pathways. Novel OAO derivatives conjugated with indomethacin (IND) were synthesized, and their effect on the activation and expression of Nrf2 and NF-κB in HepG2 hepatoma cells and THLE-2 immortalized normal hepatocytes was evaluated in relation to cell cycle arrest and apoptosis. Treatment with OAO-IND conjugates reduced the activation of Nrf2 and NF-κB and the expression of their active forms in HepG2 cells, while in normal hepatocytes, the activation of Nrf2 was increased and NF-κB diminished. Compounds 3d , 3-indomethacinoxyiminoolean-12-en-28-oic acid morpholide, and 3c , 3-indomethacinoxyiminoolean-12-en-28-oic acid benzyl ester, were the most efficient. In THLE-2 cells, as opposed to HepG2 cells, the expressions of SOD-1 and NQO1 were significantly enhanced after treatment with these compounds. The COX-2 expression was diminished in both cell lines. OAO-IND derivatives affected the cell cycle arrest at G2/M, leading to increased apoptosis and increased number of resting HepG2 cells. Therefore, the conjugation of IND with OAO derivatives may preserve cancer cells against chemoresistance through the inhibition of the Nrf2-ARE pathway and NF-κB and, at the same time, exert a chemopreventive effect in normal hepatocytes.