Synthesis and Biological Evaluation of novel Quinoxaline containing N-substituted thiazolidine-2,4-dione derivatives as Anti-cancer Agents

Introduction: Quinoxalines belong to the N-containing heterocyclic compounds that stand out as having promising biological activity due to their privileged scaffold. Quinoxaline derivatives constitute the basis of many insecticides, fungicides, herbicides, as well as being important in human health and as receptor antagonists. On the other, the compounds containing thiazolidine-2,4-dione have demonstrated wide range of pharmacological activities, which include antimicrobial, antiviral, antidiabetic and anticancer activity. In this research, we have synthesised a new quinoxaline derivatives containing N-substituted thiazolidine-2,4-dione derivatives and evaluated for antitumor activity against a 3-cell line panel, consisting of MCF7 (breast), NCI-H460 (lung), and SF-268 (CNS). Methods and Results: In a 250 ml three necked flask equipped with teflon coated mechanical stir bar, chloroacetic acid and thiourea have been dissolved in distilled water and the contents of the flask were heated in the presence of hydrochloric acid. The precipitate was filtered and washed with water and dried before recrystalization. Consequently, the new synthesized thiazolidinedione derivatives were condensed in situ by quinoxaline aldehydes and substituted benzyl halides in N,N-Dimethylformamide. The resulted products were washed with water and then recrystallized in appropriate solvent. Structures of all the synthesized compounds were confirmed by IR, 1H NMR, 13CNMR, and Mass spectral data. The MTT assay of synthesized hybrids showed promising and effective anti-cancer activity against 3-cell cell lines. The current results indicate that these quinoxaline derivatives are novel and promising agents for further development towards a treatment for cancer. conclusion: In the present study, series of new N-thiazolidine-2,4-dione incorporated quinoxaline ring were synthesized. All compounds were screened against two different cancer cell lines using MTT assay method

Synthesis of New Derivative of pyrazolo[4,5-b]quinoxaline Bearing imidazolidine-2,4-dione as a Potential Anticancer Agent

Introduction: Among heterocyclic anticancer compounds, quinoxalines and imidazolidine-2,4-dione are the most prominent since they constitute important classes of natural products and synthetic pharmaceuticals. In general, they are used as valuable intermediates and building blocks in pharmaceutical synthesis. Therefore, much attention has been paid to the synthesis of quinoxaline derivatives bearing imidazolidine-2,4-dione either by classic methods or by multicomponent reactions.  Methods and Results: The title compound was prepared through a three- step procedure. In the first step, equimolar amounts of D-glucose and o-phenylenediamine were reacted with phenyl hydrazine in the presence of acetic acid, to form the pyrazolo[4,5-b]quinoxaline  derivative. The second step involved oxidation of the resulted compound by use of sodium metaperioddate. Finally, the related aldehyde was condensed by imidazolidine-2,4-dione to yield the corresponding 3-alkylidene pyrazolo[4,5-b]quinoxaline . Conclusions: The procedure applied in this study established a convenient method for the preparation of the title compounds. The process was straight forward and it used abundant and readily available staring materials. Due to its chemical structure, and in particular the presence of the quinioxaline ring, which is a commonly encountered motif in compounds of medicinal interest, the prepared product is expected to show anticancer activity

Bioremediation of methyl tertiary-butyl ether (MTBE) by three pure bacterial cultures

Background: Bioremediation of groundwater and soil contamination is more economical than physicochemical remediation. The present study focused on the bioremediation capability of two bacterial species (Klebsiella planticola and Enterobacter cloacae) from the family Enterobacteriaceae. These bacteria have been identified as new species with capability of degrading methyl tertiary-butyl ether (MTBE). In order to enhance their degradation capability, selected concentrations and retention time were investigated. Methods: The bacteria were cultured on the nutrient agar (NA) medium at room temperature. pH of the medium was adjusted to 7. The medium was autoclaved at 121°C for 15 minutes and incubated for 24 hours at 35°C. After 24 hours, the mixture was inoculated into 50 mL of Luria Bertani (LB) liquid medium containing 50 and 150 ppm MTBE. The cultures were incubated for 2 and 5 days at 35°C and shacked on a shaker at 150 rpm. Cell concentrations of the bacteria in pure culture were determined from the optical density at 600 nm using a UV–VIS spectrophotometer. Then, the culture was centrifuged at 3800 rpm for 20 minutes. In the next step, the MTBE concentration in the supernatant was measured by gas chromatography/mass spectrometry (GC/MS, Agilent Technologies, 5975, US10304411, 5.02.07). Results: The results showed that both strains are able to grow in the presence of 50 and 150 ppm MTBE. In the best conditions, when cell density was 3×108 CFU/mL during 5 days, the highest rate of MTBE degradation for K. planticola and E. cloacae, was 43% and 40%, respectively. It was also revealed that Escherichia coli can degrade 50 and 150 ppm MTBE about 19.8% and 13.65%, respectively. Conclusion: It seems that E. coli can be a good candidate for MTBE degradation at high concentrations for a time longer than that in the present study. It was also found that the species have high performance at 50 ppm than 150 ppm. So, these bacteria can remove MTBE from the environment. Keywords: Biodegradation, Klebsiella planticola, Enterobacter cloacae, Escherichia coli, methyl tertiarybutyl ethe

Green Chemical Synthesis and Biological Evaluation of Novel N-substituted Rhodanine Derivatives as Potential Antifungal Agents

Background and purpose: In medicinal chemistry, molecules containing rhodanine(2-thiazolidine-4-one) ring as a magic multifunctional privileged structural and functional scaffold show a broad range of potent pharmacological properties containing anti-microbial, antiviral, anti-diabetic, and anti-convulsant effects. Evidence suggests that the activity of the rhodanine derivative correlates with the size and the nature of the substituents at C-5 and N-3 positions. In this study, we synthesized new N-substituted rhodanine derivatives with arylidene substituent at the C-5 position via solvent-free Knoevenagel condensation reaction. We also investigated the antifungal activity of the compounds. Materials and methods: A mixture of aromatic aldehyde (1 mmol) and rhodanin derivatives (1 mmol) was stirred in choline chloride (ChCl)/urea deep eutectic solvent (1 mL) at 100C in an oil bath for 1 hour. The progress of the reaction was monitored by TLC (2:1 n-hexane/ethyl acetate). Then, the crude compound was collected by vacuum filtration and washed using ice-cold solvent. Results: Novel products were elucidated on the basis of elemental analyses as well as FTIR, Mass and 1H NMR, 13CNMR spectroscopy. Conclusion: A green, comfortable and rapid procedure has been developed for the synthesis of N-substituted rhodanine derivatives using ChCl/Urea Deep Eutectic Ionic Liquid (DEILs) under solvent-free conditions

Hypothermic activity of acetaminophen; Involvement of GABAA receptor, theoretical and experimental studies

Objective(s):The mechanism of hypothermia action of acetaminophen (APAP) remains unclear even 125 years after its synthesis. Acetaminophen produces hypothermia. The mechanism of this reduction in core body temperature is not clear but evidence shows that it is not dependent on opioid and cannabinoid receptors. Because of strong documents about the roles of GABA and benzodiazepine receptors in hypothemic activity of some drugs such as diazepam, we determined if these receptors also contributes to the hypothermic effect of APAP. Materials and Methods: Diazepam (5 mg/kg, IP) was used for induction of hypothermia. Flumazenil (10 mg/kg, IP) or picrotoxin (2 mg/kg, IP) used for reversal of this effect. Rats injected with APAP (100, 200 or 300 mg/kg, IP). Baseline temperature measurements were taken with a digital thermometer via rectum. To evaluate the structural correlation between APAP and benzodiazepine receptor ligands, numerous models are selected and studied at HF/6-31G* level of theory. Relative energies, enthalpies and Gibbs free energies were calculated for all selected drugs. Results:Diazepam induced hypothermia was reversed by flumazenil or picrotoxin. Rats injected with APAP displayed dose- and time-related hypothermia. For combined administration, the hypothermic effect of APAP (200 mg/kg) was strongly reduced by pretreatment with picrotoxin or flumazenil

A facile method for regioselective synthesis of new N-acetyl/thioacetyl-<i>(E</i>)-stilbene benzenesulfonamide derivatives via N-acetyl/thioacetyl sulfonamide formation

<p>A series of new N-acetyl/thioacetyl-(<i>E</i>)-stilbene benzenesulfonamide derivatives were synthesized regioselectively in moderate to high yields by following a convenient, three-step procedure. The procedure consists of the direct oxidative conversion of a thiol compound to the corresponding sulfonyl chloride using TMSCl/KNO₃, followed by a room temperature reaction in a one-pot transformation of the resultant sulfonyl chloride into N-acetyl/thioacetyl sulfonamide, which undergoes a further Pd-catalyzed coupling reaction, giving rise to the stilbene compounds reported for the first time.</p