Combinatorial Chemistry & High Throughput Screening - Volume 21, Issue 4, 2018

Background: Heterocycles have extended into widespread use for generating large collection of molecules in multi-component reactions. The development of new strategies for fused pyrimidobenzothiazole system has remained a highly attractive but challenging proposition for scientists working all around. Objective: The main objective of this work is to explore the utility of different catalysts as an ecofriendly reaction medium for green Biginellis reaction. Method: A detailed study of Biginellis reactions using various catalysts was done using different research tools. The methods involved reaction of equimolar mixture of benzothiazole, 1,3-diketone and aldehyde as reactants by conventional and greener pathways via Knoevenagal condensation. Results: The present review has several significant advantages for the scientists regarding green synthesis viz. green conditions, short reaction times, high yields, clean reaction conditions, easy isolation of products, simple work-up procedure and mild reaction conditions. Conclusion: Our report gives an overview of the combinatorial libraries for fused benzothiazole entities using metal catalyst, acid catalyst, ionic liquids, phase transfer catalyst, nano catalyst, etc.

Aim and Objective: The present method is simple, green and highly efficient for the synthesis of 2-amino-4H-pyran derivatives which are achieved by a one pot three component cyclocondensation of aldehyde, malanonitrile and ethyl acetoacetate or methyl acetoacetate using DABCO under solvent free with grinding conditions at room temperature. Material and Methods: Some of the synthesized compounds were screened for their antimicrobial and antifungal activity. The study shows that these compounds show good antimicrobial activity. Furthermore, eight of the synthesized compounds were selected for screening of their anticancer activity against human astrocytoma-glioblastoma cell line (U373MG). Some of the compounds show good anticancer activity. Result: Grinding synthesis of 2-amino-4H-pyran derivatives catalyzed by DABCO with various aromatic aldehydes under solvent-free conditions at room temperature was examined. The obtained compounds (22 entries) were well synthesized in good to excellent yields. Conclusion: The present method is simple, rapid, and most efficient green protocol for the synthesis of 2-amino-4H-pyran derivatives using highly inexpensive and easily available DABCO as an efficient catalyst under grinding and solvent free condition at room temperature.

Background: More than 2,000 chemicals have been used in the tannery industry. Although some tannery chemicals have been reported to have harmful effects on both human health and the environment, only a few have been subjected to genotoxicity and cytotoxicity evaluations. Objective: This study focused on cytotoxicity and genotoxicity of ten tannery chemicals widely used in China. Materials and Methods: DNA-damaging effects were measured using the SOS/umu test with Salmonella typhimurium TA1535/pSK1002. Chromosome-damaging and cytotoxic effects were determined with the high-content in vitro Micronucleus test (MN test) using the human-derived cell lines MGC-803 and A549. Conclusion: The cytotoxicity of the ten tannery chemicals differed somewhat between the two cell assays, with A549 cells being more sensitive than MGC-803 cells. None of the chemicals induced DNA damage before metabolism, but one was found to have DNA-damaging effects on metabolism. Four of the chemicals, DY64, SB1, DB71 and RR120, were found to have chromosome-damaging effects. A Quantitative Structure-Activity Relationship (QSAR) analysis indicated that one structural feature favouring chemical genotoxicity, Hacceptor-path3-Hacceptor, may contribute to the chromosome-damaging effects of the four MN-test-positive chemicals.

Aim and Objective: The multi-component condensation of benzil, primary amines, ammonium acetate and various aldehydes was efficiently catalyzed using cobalt oxide nanoparticles under ultrasonic irradiation. This approach describes an effective and facile method for the synthesis of some novel 1,2,4,5-tetrasubstituted imidazole derivatives with several advantages such as high yields and short reaction times and reusability of the catalyst. Moreover, the prepared heterocyclic compounds showed high antibacterial activity against some pathogenic strains. Materials and Method: The facile and efficient approaches for the preparation of Co3O4 nanoparticles were carried out by one step method. The synthesized heterogeneous nanocatalyst was characterized by spectroscopic analysis including EDX, FE-SEM, VSM, XRD and FT-IR analysis. The as-synthesized cobalt oxide nanoparticles showed paramagnetic behaviour in magnetic field. In addition, the catalytic influence of the nanocatalyst was examined in the one-pot reaction of primary amines, benzil, ammonium acetate and diverse aromatic aldehydes under ultrasonic irradiation. All of the 1,2,4,5-tetrasubstituted imidazoles were investigated and checked with m.p., 1H NMR, 13C NMR and FT-IR spectroscopy techniques. The antibacterial properties of the heterocycles were evaluated in vitro by the disk diffusion against pathogenic strains such as Escherichia coli (EC), Bacillus subtillis (BS), Staphylococcus aureus (SA), Salmonellatyphi (ST) and Shigella dysentrae (SD) species. Results: In this research cobalt oxide nanostructure was used as a robust and green catalyst in the some novel imidazoles. The average particle size measured from the FE-SEM image is found to be 20-30 nm which confirmed to the obtained results from XRD pattern. Various electron-donating and electron-withdrawing aryl aldehydes were efficiently reacted in the presence of Co3O4 nanoparticles. The role of the catalyst as a Lewis acid is promoting the reactions with the increase in the electrophilicity of the carbonyl and double band groups. To investigate the reusability of the catalyst, the model study was repeated using recovered cobalt oxide nanoparticles. The results showed that the nanocatalyst could be reused for five times with a minimal loss of its activity. Conclusion: We have developed an efficient and environmentally friendly method for the synthesis of some tetrasubstituted imidazoles via three-component reaction of benzil, primary amines, ammonium acetate and various aldehydes using Co3O4 NPs. The present approach suggests different benefits such as: excellent yields, short reaction times, simple workup procedure and recyclability of the magnetic nanocatalyst. The prepared 1,2,4,5-tetrasubstituted imidazoles revealed high antibacterial activities and can be useful in many biomedical applications.

Aim and Objective: Origanum acutidens (Hand.–Mazz.) Ietsw. is an endemic and perennial plant grown mainly in East Anatolia. Recently, natural plant products have attracted interest due to their safety and therapeutic effects. Therefore, the aim of this study was to investigate phytochemical contents and biological effects of Origanum acutidens. Materials and Methods: The aerial parts of O. acutidens were extracted with water, ethyl acetate, nbutanol, and methanol/chloroform solvents. Phenolic compounds and other constituents of the extracts were analyzed by HPLC/TOF-MS. The Ethyl Acetate extract (EA) was fractionated by flash chromatography. The extracts and fractions were investigated for their antiproliferative activities on human cervical adenocarcinoma (HeLa) cell line by using BrdU ELISA assay. Antioxidant activities of the extracts and fractions were evaluated by complementary test systems, namely determination of total phenolic contents, metal chelating ability and DPPH radical scavenging assay. Results: Among the extracts, Ethyl Acetate extract (EA) exhibited the highest antiproliferative activity (IC50 = 15.71 ± 0.04 μg/mL) on HeLa cells. It was therefore fractionated by flash chromatography to obtain 10 fractions which were investigated for their phenolic compounds and bioactivities. Rosmarinic acid was determined as the major component of EA and its fractions. EA exhibited higher antiproliferative activity against HeLa cell line than its fractions and 5-fluorouracil (5-FU) at the concentration of 100 μg/mL. EA and its fractions (F10, F6, F4, F7, F3, and F2) displayed higher radical scavenging activity compared to Butylated Hydroxytoluene (BHT). These effects may be attributed to the presence of rosmarinic acid in EA and its active fractions. Conclusion: This study demonstrated that O. acutidens is an essential natural source of polyphenols and a potent natural antioxidant and antiproliferative agent for food and pharmaceutical industries.

Background: In recent years, Staphylococcus aureus have developed resistance to medicines used for the treatment of human infections. Therefore, the search for antibacterial agents of high potency against Staphylococcus aureus is of great concern. Peptide deformylase (PDF), a metalloprotease catalyzing the removal of a formyl group from newly synthesized proteins, has been considered to be an important antibacterial drug target. Objective: To discover novel antibacterial drugs based on Staphylococcus aureus peptide deformylase. Method: PDF-based virtual screening of compounds from Traditional Chinese Medicine Database@Taiwan was performed by Sybyl X2.1 Surflex dock software. Compounds which possess high docking score were used for the following antibacterial experiments to evaluate their antibacterial activities. Kanamycin was also used in the antibacterial experiment as a control substance in the assay. Furthermore, molecular docking studies was applied to elucidate binding interaction between some compounds and PDF. In silico pharmacokinetic and toxicity prediction was explored to explain the reasons why these compounds might stand good chance of providing some pharmaceutical benefits. Results: Gentiopicroside, protosappanin B, dihydromyricetin and cryptochlorogenic acid with high docking score were used for our subsequent antibacterial assays. The Minimum Inhibitory Concentration (MIC) of kanamycin and gentiopicroside were 0.008 mg·mL-1 and 0.431 mg·mL-1, respectively, other three compounds, protosappanin B, dihydromyricetin and cryptochlorogenic acid have close MIC value of 0.50 mg·mL-1. Conclusion: Dihydromyricetin, with the MIC value of 0.50 mg·mL-1 and relatively high drug score of 0.82, may serve as a novel antibacterial lead compound.

Aim and Objective: The reaction of cyclohexylisocyanide and 2-aminopyridine-3- carboxylic acid in the presence of benzaldehyde derivatives in ethanol led to 3-(cyclohexylamino)-2- arylimidazo[1,2-a]pyridine-8-carboxylic acids in high yields. In a three component condensation reaction, isocyanide reacts with 2-aminopyridine-3-carboxylic acid and aromatic aldehydes without any prior activation. Material and Methods: The synthesized products have stable structures which have been characterized by IR, 1H, 13C and Mass spectroscopy as well as CHN-O analysis. Results: In continuation of our attempts to develop simple one-pot routes for the synthesis of 3- (cyclohexylamino)-2-arylimidazo[1,2-a]pyridine-8-carboxylic acids, aromatic aldehydes with divers substituted show a high performance. Conclusion: In conclusion, this study introduces the art of combinatorial chemistry using a simple one-pot procedure for the synthesis of new materials which are interesting compounds in medicinal and biological sciences.

Aim & Scope: The synthesis of highly substituted piperidine from the one-pot reaction between aromatic aldehydes, anilines and β-ketoesters in the presence of tartaric acid as a catalyst has been investigated in both methanol and ethanol media at ambient temperature. Different conditions of temperature and solvent were employed for calculating the thermodynamic parameters and obtaining an experimental approach to the kinetics and mechanism. Experiments were carried out under different temperature and solvent conditions. Material and Methods: Products were characterized by comparison of physical data with authentic samples and spectroscopic data (IR and NMR). Rate constants are presented as an average of several kinetic runs (at least 6-10) and are reproducible within ± 3%. The overall rate of reaction is followed by monitoring the absorbance changes of the products versus time on a Varian (Model Cary Bio- 300) UV-vis spectrophotometer with a 10 mm light-path cell. Results: The best result was achieved in the presence of 0.075 g (0.1 M) of catalyst and 5 mL methanol at ambient temperature. When the reaction was carried out under solvent-free conditions, the product was obtained in a moderate yield (25%). Methanol was optimized as a desirable solvent in the synthesis of piperidine, nevertheless, ethanol in a kinetic investigation had none effect on the enhancement of the reaction rate than methanol. Based on the spectral data, the overall order of the reaction followed the second order kinetics. The results showed that the first step of the reaction mechanism is a rate determining step. Conclusion: The use of tartaric acid has many advantages such as mild reaction conditions, simple and readily available precursors and inexpensive catalyst. The proposed mechanism was confirmed by experimental results and a steady state approximation.