Semicarbazides Carrying Indole Core: Synthesis, Cytotoxicity Evaluation against Human Breast Cancer Cell Lines, and Molecular Modeling Studies.

In this article, we report the synthesis and cytotoxicity evaluation of novel indole-carrying semicarbazide derivatives (IS1-IS15). The target molecules were obtained by the reaction of aryl/alkyl isocyanates with 1H-indole-2-carbohydrazide that was in-house synthesized from 1H-indole-2-carboxylic acid. Following structural characterization by 1 H-NMR, 13 C-NMR, and HR-MS, IS1-IS15 were investigated for their cytotoxic activity against human breast cancer cell lines, MCF-7 and MDA-MB-231. According to the data obtained from the MTT assay, phenyl ring with a lipophilic group at its para-position and alkyl moiety were preferential substituents on the indole-semicarbazide scaffold for antiproliferative activity. The effect of IS12 (N-(4-chloro-3-(trifluoromethyl)phenyl)-2-(1H-indole-2-carbonyl)hydrazine-1-carboxamide), the compound that demonstrated remarkable antiproliferative activity on both cell lines, was also evaluated on the apoptotic pathway. Moreover, the calculation of critical descriptors constituting drug-likeness confirmed the position of the selected compounds in the anticancer drug development process. Finally, molecular docking studies suggested the inhibition of tubulin polymerization as the potential activity mechanism of this class of molecules.

Magnetically separable nickel ferrite supported palladium nanoparticles: Highly reusable catalyst in Sonogashira cross-coupling reaction.

There is an increasing attention in developing highly efficient and reusable palladium-based catalysts used for the coupling reactions due to the high cost of palladium metal salts. Magnetically separable palladium nanoparticles have a high potential to be used as catalysts in numerous organic reactions due to their facile separation from the reaction medium by an external magnet. Herein, NiFe2O4 supported palladium nanoparticles (Pd/NiFe2O4) were successfully prepared by impregnation and reduction method in water and used as catalysts for Sonogashira cross-coupling reactions. Magnetically separable Pd/NiFe2O4 catalysts were found to be highly active and reusable in this reaction. Pd/NiFe2O4 provided an outstanding turnover frequency value (106.4 h-1) in the reaction between phenylacetylene and iodobenzene in ethanol at 70 °C and it was also found to be highly active in the water. Magnetically separable Pd/NiFe2O4 exhibited high catalytic performance even after the tenth use in this reaction.

Seasonal distribution and risk assessment of polycyclic aromatic hydrocarbons (PAHs) in surface sediments from the Giresun coast of southeastern Black Sea.

Seasonal sediment samples were collected along the Giresun coastline of southeastern Black Sea and analyzed to detect the levels of 16 polycyclic aromatic hydrocarbons (PAHs). The PAH levels, ranging from 28.47 to 444.36 ng g-1 with the mean of 102.57 ng g-1 remained lower than those detected in most of the other sediment studies conducted worldwide. The percentage of three-ring PAHs (38.9%) was rather high, followed by that of 5-ring PAHs (21.8%). Detection rates revealed that PAHs in surface sediments along the Giresun coastline are mainly associated with coal combustion and local emissions. The evaluation with sediment quality guidelines (SQGs) showed that the level of PAHs was comparable to that at which the risk of adverse biological effects cannot be ruled out (≥TEL and

1,3-Disubstituted urea derivatives: Synthesis, antimicrobial activity evaluation and in silico studies.

The development of new antimicrobial compounds is in high demand to overcome the emerging drug resistance against infectious microbial pathogens. In the present study, we carried out the extensive antimicrobial screening of disubstituted urea derivatives. In addition to the classical synthesis of urea compounds by the reaction of amines and isocyanates, we also applied a new route including bromination, oxidation and azidination reactions, respectively, to convert 2-amino-3-methylpyridine to 1,3-disubstituted urea derivatives using various amines. The evaluation of antimicrobial activities against various bacterial strains, Candida albicans as well as Mycobacterium tuberculosis resulted in the discovery of new active molecules. Among them, two compounds, which have the lowest MIC values on Pseudomonas aeruginosa, were further evaluated for their inhibition capacities of biofilm formation. In order to evaluate their potential mechanism of biofilm inhibition, these two compounds were docked into the active site of LasR, which is the transcriptional regulator of bacterial signaling mechanism known as quorum sensing. Finally, the theoretical parameters of the bioactive molecules were calculated to establish their drug-likeness properties.

Intramolecular Gold-Catalyzed and NaH-Supported Cyclization Reactions of N-Propargyl Indole Derivatives with Pyrazole and Pyrrole Rings: Synthesis of Pyrazolodiazepinoindole, Pyrazolopyrazinoindole, and Pyrrolopyrazinoindole.

Gold-catalyzed and NaH-supported intramolecular cyclization of N-propargyl indole derivatives with pyrazole and pyrrole units attached to indole is described. An efficient route to the synthesis of pyrazolodiazepinoindole, pyrazolopyrazinoindole, and pyrrolopyrazinoindole has been established. First, N-propargyl 2-(1H-pyrazol-5-yl)-1H-indole and 2-(1H-pyrrol-2-yl)-1H-indole were synthesized. Introduction of various substituents into the alkyne functionality was accomplished by Sonogashira cross-coupling reaction. Gold-catalyzed cyclization of pyrazoles having a terminal alkyne afforded the 6-exo-dig cyclization product. However, exclusive formation of 7-endo-dig cyclization products was observed with internal alkynes. On the other hand, cyclization with NaH only resulted in the formation of 6-exo-dig cyclization products regardless of the substitution of the alkyne functionality. Allenic intermediates were postulated for this outcome.

Gold-catalyzed oxime-oxime rearrangement.

The gold-catalyzed reaction of pyrrole and indole oximes having a propargyl group attached to the nitrogen atom was studied. The selective 6-endo-dig mode of cyclization was observed for the terminal alkynes giving rise to the formation of pyrazine N-oxides in the presence of a gold catalyst. However, the reaction with substituted alkyne transferred the oxime functionality intramolecularly from one carbon atom to another via the 7-endo-dig cyclization process. This transformation is unprecedented in the literature and is named an oxime-oxime rearrangement.