Novel heterocyclic hybrids of pyrazole targeting dihydrofolate reductase: design, biological evaluation and in silico studies.

A novel series of pyrazole analogues including hydrazones, pyrazolo[4,3-c]-pyridazines, pyrazolo[3,4-e][1,2,4]triazine and pyrazolo[3,4-d][1,2,3]triazoles was designed, synthesised and screened for their in vitro antimicrobial and DHFR inhibition activity. Compounds bearing benzenesulphonamide moiety incorporated with 3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene) hydrazine 3a or 6-amino-7-cyano-3-methyl-5H-pyrazolo[4,3-c]pyridazine 6a revealed excellent and broad spectrum antimicrobial activity comparable to ciprofloxacin and amphotericin B as positive antibiotic and antifungal controls, respectively. Furthermore, these derivatives proved to be the most active DHFR inhibitors with IC50 values 0.11 ± 1.05 and 0.09 ± 0.91 µM, in comparison with methotrexate (IC50 = 0.14 ± 1.25 µM). The in silico studies were done to calculate the drug-likeness and toxicity risk parameters of the newly synthesised derivatives. Additionally, the high potency of the pyrazole derivatives bearing sulphonamide against DHFR was confirmed with molecular docking and might be used as an optimum lead for further modification.

Synthesis, Antimicrobial Activity and Molecular Docking of Novel Thiourea Derivatives Tagged with Thiadiazole, Imidazole and Triazine Moieties as Potential DNA Gyrase and Topoisomerase IV Inhibitors.

To develop new antimicrobial agents, a series of novel thiourea derivatives incorporated with different moieties 2-13 was designed and synthesized and their biological activities were evaluated. Compounds 7a, 7b and 8 exhibited excellent antimicrobial activity against all Gram-positive and Gram-negative bacteria, and the fungal Aspergillus flavus with minimum inhibitory concentration (MIC) values ranged from 0.95 ± 0.22 to 3.25 ± 1.00 µg/mL. Furthermore, cytotoxicity studies against MCF-7 cells revealed that compounds 7a and 7b were the most potent with IC50 values of 10.17 ± 0.65 and 11.59 ± 0.59 µM, respectively. On the other hand, the tested compounds were less toxic against normal kidney epithelial cell lines (Vero cells). The in vitro enzyme inhibition assay of 8 displayed excellent inhibitory activity against Escherichia coli DNA B gyrase and moderate one against E. coli Topoisomerase IV (IC50 = 0.33 ± 1.25 and 19.72 ± 1.00 µM, respectively) in comparison with novobiocin (IC50 values 0.28 ± 1.45 and 10.65 ± 1.02 µM, respectively). Finally, the molecular docking was done to position compound 8 into the E. coli DNA B and Topoisomerase IV active pockets to explore the probable binding conformation. In summary, compound 8 may serve as a potential dual E. coli DNA B and Topoisomerase IV inhibitor.

Chiral Pyridine-3,5-bis- (L-phenylalaninyl-L-leucinyl) Schiff Base Peptides as Potential Anticancer Agents: Design, Synthesis, and Molecular Docking Studies Targeting Lactate Dehydrogenase-A.

A series of branched tetrapeptide Schiff bases 3-6 were designed and synthesized from corresponding tetrapeptide hydrazide 2 as a starting material.In vitroevaluation of the synthesized compounds 4-6 against breast MCF-7 carcinoma cells identified their excellent anticancer potency, with IC50 ranging from 8.12 ± 0.14 to 17.55 ± 0.27 µM in comparison with the references, cisplatin and milaplatin (IC50= 13.34 ± 0.11and 18.43 ± 0.13 µM, respectively). Furthermore, all derivatives demonstrated promising activity upon evaluation of theirin vitroandin vivosuppression of p53 ubiquitination and inhibition assessment for LDHA kinase. Finally, molecular docking studies were performed to predict the possible binding features of the potent derivatives within the ATP pocket of LDHA in an attempt to get a lead for developing a more potent LDHA inhibitor with anti-proliferative potency.

Anticancer Activities of Newly Synthesized Chiral Macrocyclic Heptapeptide Candidates.

As important cancer therapeutic agents, macrocyclic peptides have recently drawn great attention, mainly because they are synthetically accessible and have lower toxicity towards normal cells. In the present work, we synthesized newly macrocyclic pyridoheptapeptide derivatives. The synthesized derivatives were characterized using standard chemical and spectroscopic analytical techniques, and their anticancer activities against human breast and hepatocellular cancer cells were investigated. Results showed that compounds 1a and 1b were the most effective against hepatocellular (HepG2) and breast (MCF-7) cancer cell lines, respectively.

A New Validated Potentiometric Method for Sulfite Assay in Beverages Using Cobalt(II) Phthalocyanine as a Sensory Recognition Element.

A simple potentiometric sensor is described for accurate, precise, and rapid determination of sulfite additives in beverages. The sensor is based on the use of cobalt phthalocyanine as a recognition material, dispersed in a plasticized poly(vinyl chloride) matrix membrane. o-Nitrophenyl octyl ether (o-NPOE) as a membrane solvent and tri-dodecylmethyl- ammonium chloride (TDMAC) as ion discriminators are used as membrane additives. Under the optimized conditions, sulfite ion is accurately and precisely measured under batch and flow injection modes of analysis. The sensor exhibits fast and linear response for 1.0 × 10-2-1.0 × 10-6 M (800-0.08 µg/mL) and 1.0 × 10-1-5.0 × 10-5 M (8000-4 µg/mL) sulfite with Nernstian slopes of -27.4 ± 0.3 and -23.7 ± 0.6 mV/concentration decade under static and hydrodynamic modes of operation, respectively. Results in good agreement with the standard iodometric method are obtained.Validation of the assay method is examined in details including precision, accuracy, bias, trueness, repeatability, reproducibility, and uncertainty and good performance characteristics of the method are obtained. The sensor response is stable over the pH range of 5 to 7 without any significant interference from most common anions. The advantages offered by the proposed sensor (i.e., wide range of assay, high accuracy and precision, low detection limit, reasonable selectivity, long term response stability, fast response, and long life span and absence of any sample pretreatment steps) suggest its use in the quality control/quality assurance routine tests in beverages industries, toxicological laboratories and by inspection authorities.

Antiulcerogenic effect of Cuphea ignea extract against ethanol-induced gastric ulcer in rats.

BACKGROUND: Cuphea ignea is one of the herbal resources belonging to Lythraceae family. Some species of this family have been used traditionally in South and Central America's folk medicine for treating stomach disorders. Therefore, the present study was performed to evaluate the gastropreventive effect of aqueous ethanolic extract of C. ignea aerial parts on ethanol-induced gastric ulcer. METHODS: Gastric ulcers were induced in Sprague Dawley rats using one oral dose of absolute ethanol (1.5 mL/rat). The C. ignea aerial parts extract at doses of 250 and 500 mg/kg body weight and ranitidine (a reference drug) at a dose of 30 mg/kg body weight were orally administrated daily for 7 days before ulcer induction. One hour after ethanol administration blood samples were collected and then stomachs of sacrificed rats were subjected to biochemical, macroscopic and microscopic studies. RESULTS: Oral administration of C. ignea extract significantly attenuated gastric ulcer as revealed by significant reduction in the gastric ulcer index and volume of gastric juice while significantly increased preventive percentage, gastric pH value and pepsin activity. Pre-treatment of C. ignea extract markedly improved the serum level of TNF-α, the gastric MPO activity and NO content. Furthermore, C. ignea pre-treatment significantly increased the gastric levels of enzymatic and non- enzymatic antioxidants namely CAT, SOD, GSH-Px, and GSH with concomitant reduction in MDA level compared with those in the ethanol group. These results were further supported by histopathological findings which revealed the curing effect of C. ignea on the hemorrhagic shock induced by ethanol toxicity. CONCLUSIONS: C. ignea extract showed a potential gastroprotective effect on ethanol-induced gastric ulcer, and its effect may be mediated through suppression of oxidative stress and gastric inflammation.

Novel Potentiometric 2,6-Dichlorophenolindo-phenolate (DCPIP) Membrane-Based Sensors: Assessment of Their Input in the Determination of Total Phenolics and Ascorbic Acid in Beverages.

In this work, we demonstrated proof-of-concept for the use of ion-selective electrodes (ISEs) as a promising tool for the assessment of total antioxidant capacity (TAC). Novel membrane sensors for 2,6-dichlorophenolindophenolate (DCPIP) ions were prepared and characterized. The sensors membranes were based on the use of either CuII-neocuproin/2,6-dichlorophenolindo-phenolate ([Cu(Neocup)2][DCPIP]2) (sensor I), or methylene blue/2,6-dichlorophenolindophenolate (MB/DCPIP) (sensor II) ion association complexes in a plasticized PVC matrix. The sensors revealed significantly enhanced response towards DCPIP ions over the concentration range 5.13 × 10-5-1.0 × 10-2 and 5.15 × 10-5-1.0 × 10-2 M at pH 7 with detection limits of 6.3 and 9.2 µg/mL with near-Nernstian slope of -56.2±1.7 and -51.6±2 mV/decade for sensors I and II, respectively. The effects of plasticizers and various foreign common ions were also tested. The sensors showed enhanced selectivity towards DCPIP over many other phenolic and inorganic ions. Long life span, high potential stability, high reproducibility, and fast response were also observed. Method validation was also verified by measuring the detection limit, linearity range, accuracy, precision, repeatability and between-day-variability. The sensors were introduced for direct determination of TAC in fresh and canned juice samples collected from local markets. The obtained results agreed fairly well with the data obtained by the standard method.

Potent Anti-Ovarian Cancer with Inhibitor Activities on both Topoisomerase II and V600EBRAF of Synthesized Substituted Estrone Candidates.

A series of 16-(α-alkoxyalkane)-17-hydrazino-estra-1(10),2,4-trien[17,16-c]-3-ol (3a-l) and estra-1(10),2,4-trien-[17,16-c]pyrazoline-3-ol derivatives (4a-d) were synthesized from corresponding arylidines 2a,b which was prepared from estrone 1 as starting material. Condensation of 1 with aldehydes gave the corresponding arylidine derivatives 2a,b which were treated with hydrazine derivatives in alcohols to give the corresponding derivatives 3a-l, respectively. Additionally, treatment of 2a,b with methyl- or phenylhydrazine in ethanolic potassium hydroxide afforded the corresponding N-substituted pyrazoline derivatives 4a-d, respectively. All these derivatives showed potent anti-ovarian cancer both in vitro and in vivo. The mechanism of anti-ovarian cancer was suggested to process via topoisomerase II and V600EBRAF inhibition.

In Vitro and In Vivo Anti-Breast Cancer Activities of Some Newly Synthesized 5-(thiophen-2-yl)thieno-[2,3-d]pyrimidin-4-one Candidates.

In this study, some of new thiophenyl thienopyrimidinone derivatives 2-15 were prepared and tested as anti-cancer agents by using thiophenyl thieno[2,3-d]pyrimidinone derivative 2 as a starting material, which was prepared from cyclization of ethyl ester derivative 1 with formamide. Treatment of 2 with ethyl- chloroacetate gave thienopyrimidinone N-ethylacetate 3, which was reacted with hydrazine hydrate or anthranilic acid to afford acetohydrazide 4 and benzo[d][1,3]oxazin-4-one 5, respectively. Condensation of 4 with aromatic aldehydes or phenylisothiocyanate yielded Schiff base derivatives 6,7, and thiosemicarbazise 10, which were treated with 2-mercaptoacetic acid or chloroacetic acid to give the corresponding thiazolidinones 8, 9, and phenylimino-thiazolidinone 11, respectively. Treatment of 4 with ethylacetoacetate or acetic acid/acetic anhydride gave pyrazole 12 and acetyl acetohydrazide 13 derivatives, respectively. The latter compound 13 was reacted with ethyl cycno-acetate or malononitrile to give 14 and 15, respectively. In this work, we have studied the anti-cancer activity of the synthesized thienopyrimidinone derivatives against MCF-7 and MCF-10A cancer cells. Furthermore, in vivo experiments showed that the synthesized compounds significantly reduced tumor growth up to the 8th day of treatment in comparison to control animal models. Additionally, the synthesized derivatives showed potential inhibitory effects against pim-1 kinase activities.

Design, Synthesis, Anticancer Evaluation and Molecular Modeling of Novel Estrogen Derivatives.

A series of estrone derivatives 3⁻8 was designed and synthesized using estrone arylmethylenes 2a,b as starting materials and their structures were confirmed by different spectral data and elemental analyses. All the newly synthesized compounds exhibited potent in vitro and in vivo cytotoxic activities against breast cancer cell lines. In addition, all compounds were subjected to in vitro and in vivo inhibition assays for EGFR and VEGFR-2 kinases as well as p53 ubiquitination activity to obtain more details about their mechanism of action. Based on the promising results, a molecular docking study was investigated for the most representative compound 5a against the two targets, EGFR and VEGFR-2 kinases, to assess its binding affinity, hoping to rationalize and obtain potent anticancer agents in the future.

Design, Synthesis and Docking Studies of Novel Macrocyclic Pentapeptides as Anticancer Multi-Targeted Kinase Inhibitors.

A series of macrocyclic pyrido-pentapeptide candidates 2⁻6 were synthesized by using N,N-bis-[1-carboxy-2-(benzyl)]-2,6-(diaminocarbonyl)pyridine 1a,b as starting material. Structures of the newly synthesized compounds were established by IR, ¹H and 13C-NMR, and MS spectral data and elemental analysis. The in-vitro cytotoxicity activity was investigated for all compounds against MCF-7 and HepG-2 cell lines and the majority of the compounds showed potent anticancer activity against the tested cell lines in comparison with the reference drugs. Out of the macrocyclic pyrido-pentapeptide based compounds, 5c showed encouraging inhibitory activity on MCF-7 and HepG-2 cell lines with IC50 values 9.41 ± 1.25 and 7.53 ± 1.33 µM, respectively. Interestingly, 5c also demonstrated multitarget profile and excellent inhibitory activity towards VEGFR-2, CDK-2 and PDGFRß kinases. Furthermore, molecular modeling studies of the compound 5c revealed its possible binding modes into the active sites of those kinases.

Mushrooms: a potential natural source of anti-inflammatory compounds for medical applications.

For centuries, macrofungi have been used as food and medicine in different parts of the world. This is mainly attributed to their nutritional value as a potential source of carbohydrates, proteins, amino acids, and minerals. In addition, they also include many bioactive metabolites which make mushrooms and truffles common components in folk medicine, especially in Africa, the Middle East, China, and Japan. The reported medicinal effects of mushrooms include anti-inflammatory effects, with anti-inflammatory compounds of mushrooms comprising a highly diversified group in terms of their chemical structure. They include polysaccharides, terpenoids, phenolic compounds, and many other low molecular weight molecules. The aims of this review are to report the different types of bioactive metabolites and their relevant producers, as well as the different mechanisms of action of mushroom compounds as potent anti-inflammatory agents.

Antiproliferative Activity of Some Newly Synthesized Substituted Pyridine Candidates Using 4-(Aaryl)-6-(naphthalen-1-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile as Synthon.

Herein, we used nicotinonitrile derivatives 4a,b as scaffolds to build novel and active antineoplastic agents. The reaction of nicotinonitrile derivatives 4a,b with POCl3/PCl5 and/or hydrazine hydrate afforded 2-chloropyridones 6a,b and 2-hydrazinyl nicotinonitrile derivatives 11a,b, respectively, as building blocks for various heterocyclic compounds. The structures of all of the synthesized heterocycles were elucidated from their spectral and elemental analyses. The cytotoxic activities of the prepared derivatives were evaluated against different cancer cell lines. Results revealed potential cytotoxic effects of the synthesized compounds against evaluated cell lines, where NCIH 460 and RKOP 27 cell lines were the most affected by the prepared compounds. Derivative 14a was the most effective against all tested cell lines in terms of the obtained IC50 values (25 ± 2.6, 16 ± 2, 127 ± 25, 422 ± 26, and 255 ± 2 nM against NCIH 460, RKOP 27, HeLa, U937, and SKMEL 28 cells, respectively).

Low-cost potentiometric paper-based analytical device based on newly synthesized macrocyclic pyrido-pentapeptide derivatives as novel ionophores for point-of-care copper(ii) determination.

A simple, cost-effective, portable and disposable paper-based analytical device is designed and fabricated for copper(ii) determination. All solid-state ion-selective electrodes (ISEs) for copper and a Ag/AgCl reference electrode were constructed and optimized on the paper substrate. The copper electrodes were built using carbon nano-tube ink as a conductive substrate and an ion-to electron transducer. A suitable polymeric membrane is drop-cast on the surface of the conductive carbon ink window. The copper-sensing membrane is based on newly synthesized macrocyclic pyrido-pentapeptide derivatives as novel ionophores for copper detection. Under the optimized conditions, the presented all-solid-state paper-based Cu2+-ISEs showed a Nernstian response toward Cu2+ ions in 30 mM MES buffer, pH 7.0 over the linear range of 5.0 × 10-7-1.0 × 10-3 M with a limit of detection of 8.0 × 10-8 M. The copper-based sensors exhibited rapid detection of Cu2+ ions with a short response time (<10 s). The selectivity pattern of these new ionophores towards Cu2+ ions over many common mono-, di- and trivalent cations was evaluated using the modified separate solution method (MSSM). The presented paper-based analytical device exhibited good intra-day and inter day precision. The presented tool was successfully applied for trace Cu2+ detection in real samples of serum and whole blood collected from different children with autism spectrum disorder. The data obtained by the proposed potentiometric method were compared with those obtained by the inductively-coupled plasma (ICP) as a reference method. The presented copper paper-based analytical-device can be considered as an attractive tool for point-of-care copper determination because of its affordability, vast availability, and self-pumping ability, particularly when combined with potentiometric detection.

Paper-Based Potentiometric Sensors for Nicotine Determination in Smokers' Sweat.

Herein, we describe for the first time, the design and fabrication of a novel nicotine paper-based sensor, in which a miniaturized paper reference electrode is integrated for potentiometric measurements. The paper-based sensors were designed using printed wax barriers to define the electrochemical cell and the sample zones. The electrodes were based on the use of the ion association complexes of the nicotinium cation (Nic) with either tetraphenylborate (TPB) or 5-nitrobarbiturate (NB) counter anions as sensing materials for nicotine recognition. A poly (3,4 ethylenedioxythiophene)/poly-(styrene sulfonate) (PEDOT/PSS) conducting polymer was used as an ion-to-electron transducer. The performance characteristics of the proposed sensors were evaluated and it revealed a rapid and stable response with a Nernstian slope of 55.2 ± 0.3 and 51.2 ± 0.6 mV/decade over the linear range of 1.0 × 10-5 to 1.0 × 10-2 M and detection limits of 6.0 and 8.0 µM for [Nic/TPB] and [Nic/NB], respectively. The sensors revealed a constant response over the pH range 3.5-6.5. The designed sensors provided a portable, inexpensive, and disposable way of measuring trace levels of nicotine coming from different cigarettes and in the collected human sweat of heavy smokers. All results were compared favorably with those obtained by the standard gas chromatographic method.

An all-solid-state potentiometric sensor modified with multi-walled carbon nanotubes (MWCNTs) for silicate assessment and water-quality testing.

A simple and cost-effective approach is proposed for silicate ion determination. The approach is based on designing an all-solid-state potentiometric sensor. The plasticized polyvinyl chloride (PVC) membrane sensor is based on the ion-association complex [Ni(bphen)3]2+[SiO3]2- as a sensory recognition material. The sensor is modified with multi-walled carbon nanotubes (MWCNTs) as an ion-to-electron transducer material. The performance characteristics of the new silicate-selective electrode were evaluated using a potentiometric water-layer test, potentiometric measurements, impedance spectroscopy, and current-reversal chronopotentiometry. The developed electrodes exhibited a low detection limit (0.11 µg mL-1) over a wide linear range (4.0 × 10-6 to 1.0 × 10-3 M) and near-Nernstian sensitivity (slope = -28.1 ± 1.4 mV per decade). They presented a very short response time (<5 s) over the pH range 6-12 and provided acceptable reliability, ease of design and miniaturization, and high potential stability, in addition to good accuracy and precision. The sensors exhibited enhanced selectivity for silicate over many common interfering anions, such as SO42-, NO3-, CH3COO-, CO32-, Cl-, S2-, and PO43-. These results could qualify the developed sensor to be used in a successful way for the trace determination of silicate ions in different matrices. The developed method was successfully applied to the potentiometric detection of silicate in different pre-packaged bottled drinking water samples.

Liquid Contact-Selective Potentiometric Sensor Based on Imprinted Polymeric Beads Towards 17ß-Estradiol Determination.

Novel potentiometric devices "ion-selective electrodes (ISEs)" were designed and characterized for the detection of 17ß-estradiol (EST) hormone. The selective membranes were based on the use of man-tailored biomimics (i.e., molecularly imprinted polymers (MIPs)) as recognition ionophores. The synthesized MIPs include a functional monomer (methacrylic acid (MAA)) and a cross-linker (ethylene glycol dimethacrylic acid (EGDMA)) in their preparation. Changes in the membrane potential induced by the dissociated 17ß-estradiol were investigated in 50 mM CO32-/HCO3- buffer solution at pH 10.5. The ion-selective electrodes (ISEs) exhibited fast response and good sensitivity towards 17ß-estradiol with a limit of detection 1.5 µM over a linear range starts from 2.5 µM with an anionic response of 61.2 ± 1.2 mV/decade. The selectivity pattern of the proposed ISEs was also evaluated and revealed an enhanced selectivity towards EST over several phenolic compounds. Advantages revealed by the presented sensor (i.e., wide range of assay, enhanced accuracy and precision, low limit of detection, good selectivity, long-term potential stability, rapid response and long life-span and absence of any sample pretreatment steps) suggest its use in routine quality control/quality assurance tests. They were successfully applied to estradiol determination in biological fluids and in different pharmaceutical preparations collected from the local market.

A SnO2/CeO2 Nano-Composite Catalyst for Alizarin Dye Removal from Aqueous Solutions.

A new SnO2/CeO2 nano-composite catalyst was synthesized, characterized and used for the removal of alizarin dyes from aqueous solutions. The composite material was prepared using a precipitation method. X-ray powder diffractometry (XRD), high resolution transmission electron microscopy (HR-TEM), Brunauer-Emmett-Teller methodology (BET) and Fourier Transform Infrared Spectrometry (ATR-FTIR) were utilized for the characterization of the prepared composite. The prepared nano-composite revealed high affinity for the adsorption and decomposition of alizarin dyes. The adsorption capacity under different experimental conditions (adsorbate concentration, contact time, adsorbent dose and pH) was examined. Under optimized experimental conditions, the removal of alizarin yellow, alizarin red and alizarin-3-methylimino-diacetic acid dyes from aqueous solutions was about 96.4%,87.8% and 97.3%, respectively. The adsorption isotherms agreed with the models of Langmuir, Freundlich and Temkin isotherms.

Synthesis and Characterization of New Dihydronaphthalene Candidates as Potent Cytotoxic Agents against MCF-7 Human Cancer Cells.

In the present work, a new series of dihydronaphthalene derivatives were synthesized starting with 6-methoxy-1-tetralone 1, and the corresponding hydrazine derivative 2. Reaction of compound 2 with aryl isothiocyanates produced thiosemicarbazides 3a-d, which were reacted with ethyl chloroacetate to give thiazolidinone derivatives 4a-d. Pyrano thiazolecarbonitrile derivatives 5a-f were prepared by heating a mixture of compounds 4a or 4c, aryl aldehydes, and malononitrile utilizing distilled water in the presence of catalytic amount of potassium hydrogen phthalate. Also, treatment of 4a with DMF-DMA under solvent-free conditions gave enaminone derivative 6, which condensed with ethyl acetoacetate or acetylacetone or malononitrile or cyanothioacetamide to give compounds 7-10, respectively. Finally, reaction of the enaminone 6 with 2-aminoimidazol or 2-aminothiazol in the presence of glacial acetic acid produced derivatives 11 and 12, respectively. Cytotoxic evaluation of eleven compounds, against MCF-7 (human breast adenocarcinoma) cell lines, was estimated. Results revealed that five of the examined compounds 5a, 5d, 5e, 10, and 3d showed potent cytotoxic activities recording, IC50 values; 0.93 ± 0.02, 1.76 ± 0.04, 2.36 ± 0.06, 2.83 ± 0.07, and 3.73 ± 0.09 µM, respectively, which were more potent than the reference used (Saturosporin, IC506.08 ± 0.15 µM). The new products were also examined towards normal epithelial breast cells (MCF10A). All of them showed very good safety profile with different degrees and were safer than the reference drug used. Compound 5a was the most effective against MCF-7 cells and was less toxic than Saturosporin by about 18.45-folds towards MCF01A normal cells. All the new compounds were fully characterized by the different spectral and analytical tools. Herein, detailed syntheses, spectroscopic, and biological data are reported.

Synthesis and Characterization of Macrocyclic Chiral Tröger's Base Phenhomazine Candidates as Anticancer Agent.

1,4,7,10-Tetraoxa[10](2,8)trögerophane 5 was synthesized from its corresponding precursors. Heating of 2 with p-nitrophenoxide afforded bis(p-nitrophenyl)ether 3, which was treated with hydrazine hydrate to give bis(p-aminophenyl)ether 4. Treatment of 4 with paraformaldehyde and triflouroacetic anhydride gave trögerophane 5. Reaction of 5 with trifluroacetic anhydride afforded phenhomazine derivative 6, which was treated with potassium carbonate to afford tetrahydrophenhomazine 7. Finally, reaction of 7 with phenacylchloride, bromoacetic acid, or ethyl bromoacetate in the presence of triethyl amine under reflux, afforded the corresponding macrocyclic compounds 8, 9 and 10, respectively. The synthesized trögerophane,precursors and its newly synthesized phenhomazines derivatives were screened for anticancer activity. Results revealed that 1,4,7,10-tetraoxa[10](2,8)trögerophane had a promising selectivity towards colon cancer cell line with an IC50 of 92.7 µg/ml.