An In Vivo Biocatalytic Cascade Featuring an Artificial Enzyme Catalyzed New-to-Nature Reaction

Artificial enzymes utilizing the genetically encoded non-proteinogenic amino acid p-aminophenylalanine (pAF) as catalytic residue are able to react with carbonyl compounds through an iminium ion mechanism, making reactions possible that have no equivalent in nature. Here, we report an in vivo biocatalytic cascade that is augmented with such an artificial enzyme catalyzed new-to-nature reaction. The artificial enzyme in this study is a pAF containing evolved variant of the Lactococcal multidrug resistance Regulator, designated LmrR_V15pAF_RMH, which efficiently converts in vivo produced benzaldehyde derivatives into the corresponding hydrazone products inside E. coli cells. These in vivo biocatalytic cascades comprising an artificial enzyme catalyzed reactions are an important step towards achieving a hybrid metabolism.

Synthesis and characterization of azetidin-2-one and 1,3-oxazepine derivatives using Schiff bases derived from 1,1’-biphenyl-4,4’-diamine

The present study included the synthesis of two series of heterocyclic compounds, azetidin-2-one and 1,3-oxazepine derivatives. All synthesized compounds were characterized using FT-IR and 1H NMR spectra. The study was divided into two parts. The first synthesis Schiff bases derivatives (1-4) via the condensation reaction of 1,1′-biphenyl-4,4′-diamine (A) with benzaldehyde derivatives (2,5-dimethoxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde, furan-2-carbaldehyde and 3-hydroxybenzaldehyde). The second synthesis azetidine-2-one derivatives (5-8) from the reaction of Schiff bases with chloroacetyl chloride. Schiff bases also reacted with maleic anhydride to yield 1,3-oxazepine derivatives (9-12).

Copper ferrite catalyst for direct arylation of acidic C-H bonds in azoles with aryl aldehydes

Coupling reagents toward direct arylation of C2-H bonds in aryl azoles are often limited to aryl halides. Herein we report a functionalization of the acidic sp2 C-H bonds in benzothiazoles with benzaldehyde derivatives. Reactions proceeded in the presence of commercially ready CuFe2O4 catalyst. Scope of functional groups included chloro, nitro, cyano, and ester groups.

Tetramethylguanidine-functionalized melamine as a multifunctional organocatalyst for the expeditious synthesis of 1,2,4-triazoloquinazolinones

Novel nano-ordered 1,1,3,3-tetramethylguanidine-functionalized melamine (Melamine@TMG) organocatalyst was prepared and adequately identified by various techniques including FTIR, EDX, XRD and SEM spectroscopic or microscopic methods as well as TGA and DTG analytical methods. The Melamine@TMG, as an effective multifunctional organocatalyst, was found to promote smoothly the three-component synthesis of 1,2,4-triazoloquinazolinone derivatives using cyclic dimedone, 3-amino-1,2,4-triazole and different benzaldehyde derivatives in EtOH at 40 °C. This practical method afforded the desired products in high to excellent yields (86–99%) and short reaction times (10–25 min). The main advantages of this new method are the use of heterogeneous multifunctional nanocatalyst, simple work-up procedure with no need for chromatographic purification, highly selective conversion of substrates and recyclability of the catalyst, which could be used in five consecutive runs with only a small decrease in its activity.

Synthesis and Cytotoxic Activity of Several Novel N-Alkyl-Plinabulin Derivatives With Aryl Group Moieties

Seven novel N-alkyl-plinabulin derivatives with aryl groups moieties (nitroquinoline, 1,4-dihydroquinoline, 4-methoxybenzene, and 4-chlorobenzene) have been synthesized via aldol condensation and alkylation in one-pot, and tested for their cytotoxicity against 4 cancer cell lines (KB, HepG2, Lu, and MCF7). Compounds ( Z)−3-((6,8-dimethyl-4-oxo-1,4-dihydroquinolin-2-yl)methylene)−6-(( Z)−4-methoxybenzylidene)−1-(prop-2-yn-1-yl)piperazine-2,5-dione (5a), ( Z)−6-(( Z)−4-methoxybenzylidene)−1-(prop-2-yn-1-yl)−3-((1,6,8-trimethyl-4-oxo-1,4-dihydroquinolin-2-yl)methylene)piperazine-2,5-dione (5b), and ( Z)−3-(( Z)−4-chlorobenzylidene)−1,4-dimethyl-6-((8-methyl-4-nitroquinolin-2-yl)methylene)piperazine-2,5-dione (8) showed strong cytotoxicity against 3 of the cancer cells lines (KB, HepG2 and Lu) with IC50 values ranging from 3.04 to 10.62 µM. The quinoline-derived compounds had higher cytotoxic activity than the benzaldehyde derivatives. The successful synthesis of these derivatives offers useful information for the development of more potent vascular disrupting agents based on plinabulin.

Halo-phenolic metabolites and their in vitro antioxidant and cytotoxic activities from the Red Sea alga Avrainvillea amadelpha

From the green alga Avrainvillea amadelpha, two new naturally halo-benzaldehyde derivatives were isolated by various chromatographic methods along with 10 known metabolites of bromophenols, sulfonoglycolipid, and steroids. Based on the 1D and 2D NMR spectra as well as on MS data, the structures of the new compounds were identified as 5-bromo-2-(3-bromo-4-hydroxybenzyl)-3,4-dihydroxybenzaldehyde named avrainvilleal (1), and 3-iodo-4-hydroxy-benzaldehyde (2). Using SRB assay, both compounds showed mild and weak cytotoxic activity against HeLa and MCF-7 cancer cell lines, compared to the good activity of their extract (IC50 values 3.1 and 4.3 μg/mL, respectively). However, avrainvilleal (1) displayed an effective scavenged DPPH radical activity with IC50 value 3.5 μM, compared to the antioxidant quercetin with IC50 value 1.5 μM.

Synthesis and Characterization of Schiff Base Complexes of Cu(II), Co(II) and Cd(II) Derived from Ethylenediamine and Benzaldehyde Derivatives

Metal complexes of Cu(II), Co(II) and Cd(II) have been synthesized using two new Schiff base ligands, N,N'-bis(4-chlorobenzylidene)ethane-1,2-diamine (L1) and N,N'-bis(3-nitrobenzylidene) ethane-1,2-diamine (L2). The Schiff bases were prepared from the condensation reaction of ethylenediamine with benzaldehyde derivatives (4-chlorobenzaldehyde and 3-nitrobenzaldehyde). The complexes have been characterized by elemental analysis, conductivity measurements, UV-visible, FT-IR and magnetic susceptibility measurements. The magnetic susceptibility measurements and UV-visible spectral data revealed that the geometry of Cu(II) and Co(II) complexes are square planar, whereas the geometry of Cd(II) complex is tetrahedral. The molar conductance data showed that the complexes are non-electrolytic in nature. The complexes were screened for antibacterial activities against four human pathogenic bacteria viz. Escherichia coli, Shigella boydii, Bacillus cereus and Staphylococcus aureus. The results indicate that Cd(II) complex of ligand (L1) has higher antibacterial activity compared to the free ligands, but less than the standard drug, kanamycine. This suggests that the metal ion plays an important role in the antibacterial activities of complexes.