Thio Analogues of Pyrimidine Bases: Syntheses and Spectral Study of New Potentially Biologically Active 2,4-Di-Ortho-(Meta- and Para-)Bromo- (Chloro and Nitro)-Benzylthio-5-Bromouracils (and 6-Methyluracils)

Eighteen new 2,4-di-ortho- (meta- and para-) bromo-(chloro- and nitro-)benzylthio-5-bromouracils (and 6-methyluracils) have been prepared. The structures of these compounds were confirmed by spectral (IR, UV/vis, ¹H NMR) and elemental analyses. Estimation of pharmacotherapeutic potential has been made for synthesized compounds on the basis of prediction of activity spectra for substances (PASS).     

Bioactive meroditerpenes and indole alkaloids from the soil fungus Neosartorya fischeri (KUFC 6344), and the marine-derived fungi Neosartorya laciniosa (KUFC 7896) and Neosartorya tsunodae (KUFC 9213)

Two new metabolites including a new aszonalenin analogue (1c) and a new meroditerpene (3) were isolated, together with aszonalenin (1a), acetylaszonalenin (1b), 13-oxofumitremorgin B (2), aszonapyrone A (4b) and helvolic acid, from the culture of the soil fungus Neosartorya fischeri (KUFC 6344). While the ethyl acetate extract of the culture of the diseased coral-derived fungus Neosartorya laciniosa (KUFC 7896) furnished aszonapyrone B (4a), aszonapyrone A (4b), tryptoquivaline L and 3′-(4-oxoquinazolin-3-yl) spiro[1H-indole-3,5′-oxolane]-2,2′-dione, the ethyl acetate extract of the culture of the marine sponge-associated fungus Neosartorya tsunodae (KUFC 9213) yielded a new analogue of chevalone C (5) and helvolic acid. The structures of the new compounds were established based on 1D and 2D NMR spectral analysis as well as HR-ESIMS. Compounds 1a–c, 2, 3, 4a, 4b and 5 were evaluated for their in vitro growth inhibitory activity on the MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and A375-C5 (melanoma) cell lines by the protein binding dye SRB method.     

Performance of density functional theory in computing nonresonant vibrational (hyper)polarizabilities

A set of exchange‐correlation functionals, including BLYP, PBE0, B3LYP, BHandHLYP, CAM‐B3LYP, LC‐BLYP, and HSE, has been used to determine static and dynamic nonresonant (nuclear relaxation) vibrational (hyper)polarizabilities for a series of all‐trans polymethineimine (PMI) oligomers containing up to eight monomer units. These functionals are assessed against reference values obtained using the Møller–Plesset second‐order perturbation theory (MP2) and CCSD methods. For the smallest oligomer, CCSD(T) calculations confirm the choice of MP2 and CCSD as appropriate for assessing the density functionals. By and large, CAM‐B3LYP is the most successful, because it is best for the nuclear relaxation contribution to the static linear polarizability, intensity‐dependent refractive index second hyperpolarizability, static second hyperpolarizability, and is close to the best for the electro‐optical Pockels effect first hyperpolarizability. However, none of the functionals perform satisfactorily for all the vibrational (hyper)polarizabilities studied. In fact, in the case of electric field‐induced second harmonic generation all of them, as well as the Hartree–Fock approximation, yield the wrong sign. We have also found that the Pople 6–31+G(d) basis set is unreliable for computing nuclear relaxation (hyper)polarizabilities of PMI oligomers due to the spurious prediction of a nonplanar equilibrium geometry. © 2013 Wiley Periodicals, Inc.     

New synthetic methods for 2,3-diarylacridin-9(10H)-one and (E)-2-aryl-4-styrylfuro[3,2-c]quinoline derivatives

Two new synthetic methodologies for 2,3-diarylacridin-9(10H)-ones were developed. The first one involves the Heck reaction of (E)-3-iodo-2-styrylquinolin-4(1H)-ones with styrenes, leading to (E,E)-2,3-distyrylquinolin-4(1H)-ones, which when heated at high temperatures cyclize in two different ways. Electrocyclization and further in situ oxidation leads to 2,3-diarylacridin-9(10H)-ones, while tautomerization, cyclization by nucleophilic addition and further in situ oxidation produces (E)-2-aryl-4-styrylfuro[3,2-c]quinolines as the main compound. The second method gives only 2,3-diaryl-10-methylacridin-9(10H)-ones and involves the Heck reaction of (E)-3-iodo-1-methyl-2-styrylquinolin-4(1H)-ones and styrenes, leading to (E,E)-1-methyl-2,3-distyrylquinolin-4(1H)-ones, which when heated at high temperatures cyclize through electrocyclization and oxidation processes affording the expected compounds. The structures of all new compounds were established by extensive NMR studies.     

Benzodiazepines: Drugs with Chemical Skeletons Suitable for the Preparation of Metallacycles with Potential Pharmacological Activity

The synthesis of organometallic compounds with potential pharmacological activity has attracted the attention of many research groups, aiming to take advantage of aspects that the presence of the metal-carbon bond can bring to the design of new pharmaceutical drugs. In this context, we have gathered studies reported in the literature in which psychoactive benzodiazepine drugs were used as ligands in the preparation of organometallic and metal complexes and provide details on some of their biological effects. We also highlight that most commonly known benzodiazepine-based drugs display molecular features that allow the preparation of metallacycles via C-H activation. These organometallic compounds merit further attention regarding their potential biological effects, not only in terms of psychoactive drugs but also in the search for drug replacements, for example, for cancer treatments.