An efficient one-pot synthesis and docking studies of bioactive new antiproliferative dispiro[oxindole/acenaphthylenone‒benzofuranone] pyrrolidine scaffolds.

A new and efficient method has been developed to synthesize dispiro[oxindole/acenaphthylenone-benzofuranone]pyrrolidine compounds. This is done by triggering the 1,3-dipolar cycloaddition reaction of azomethine ylides by reacting isatin/acenaphthoquinone with L-picolinic acid/L-proline/sarcosine/L-thioproline/tetrahydroisoquinolines, in a highly regioselective manner in an ionic liquid [DBU][Ac] with 4'-chloro-auron[2-(4-chlorobenzylidene)benzofuran-3(2H)-one]. Single-crystal X-ray diffraction data support the proposed structures of the new compounds. The heterocycles derived from amino acids such as L-picolinic acid, L-proline, and L-thioproline showed significant inhibitory effects against six human solid tumors, including lung, breast, cervix, colon, and others. These new structures were also tested in the active sites of the MDM2 receptor to further study their antiproliferative effects.

New pyrazolyl-dibenzo[b,e][1,4]diazepinones: room temperature one-pot synthesis and biological evaluation.

Several new (5-aryloxy-pyrazolyl)- and (5-aryl/olefin-sulfanyl-pyrazolyl)-dibenzo[b,e] [1,4] diazepinone scaffolds have been synthesized, by assembling 5-substituted 3-methyl-1-phenyl-pyrazole-4-carbaldehydes of varied nature with different cyclic diketones and aromatic diamines successfully in the presence of indium chloride in acetonitrile, at room temperature. Desired products are excellent in the purity and isolated without chromatography. All new structures are confirmed, on the basis of single-crystal X-ray diffraction data of representative 29e. Compounds reported in the present work revealed good antioxidant, antimicrobial and antiproliferative activities with promising FRAP (ferric reducing antioxidant power), bacterial resistance and human solid tumor cell growth inhibitory values, respectively. Compounds 25c and 29e, overall, registered good to moderate activity against A549 (lung), HeLa (cervix), SW1573 (lung) T-47D (breast) and WiDr (colon) cell lines, with GI50 values in the 2.6-5.1 µM and 1.8-7.5 µM ranges, respectively. Molecular docking was carried out to elucidate the binding modes of the compounds (25c, 29e) to topoisomerase I and II.

Efficient synthesis and biological evaluation of new benzopyran-annulated pyrano[2,3-c]pyrazole derivatives.

A one-pot method has been described to synthesize benzopyran-annulated pyrano[2,3-c]pyrazoles, effectively by combining O-alkenyloxy/alkynyloxy-acetophenones with various pyrazolones in triethylammonium acetate (TEAA) under microwave irradiation. While combination of O-allyloxy- or O-prenyloxy-acetophenones with pyrazolones occurred efficiently, that of O-propargyloxy-acetophenones was found effective in the presence of ZnO catalyst, via a domino Knoevenagel-hetero-Diels-Alder (DKHDA) reaction. Aminobenzopyran frameworks were also synthesized, after nitro-containing products were reduced in tandem with iron(II) in an acidic medium. The in vitro antiproliferative activity of these compounds was measured and discussed against gram-positive, gram-negative and M. tuberculosis bacteria, fungi, and various representative human solid tumor cell lines, in addition to their ferric reducing antioxidant capability.

A Base-Catalyzed, Domino Aldol/hetero-Diels-Alder Synthesis of Tricyclic Pyrano[3,4-c]chromenes in Glycerol.

The domino aldol/hetero-Diels-Alder synthesis of some new tricyclic pyrano[3,4-c]chromene derivatives has been achieved successfully after assembling a variety of acyclic or cyclic monoketones with prenyl ether-tethered aldehydes in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene in glycerol at 120 °C. The hitherto unreported stereochemical outcome of this synthetic sequence was studied and established on the basis of single-crystal X-ray diffraction data and 2D NMR NOESY spectroscopy along with the isolation and characterization of the intermediate Aldol condensation product.

One-pot synthesis, biological evaluation, and docking study of new chromeno-annulated thiopyrano[2,3-c]pyrazoles.

A one-pot synthesis of new chromeno-annulated thiopyrano[2,3-c]pyrazoles has been achieved through a domino-Knoevenagel-hetero-Diels-Alder reaction after combining various pyrazol-5-thiones with O-alkenyloxy/alkynyloxy-salicylaldehydes/naphthaldehydes in a Brønsted acidic ionic liquid, [Hmim]HSO[Formula: see text], methylimidazolium hydrogen sulphate, under microwave irradiation. The method is simple and in many cases the isolated products did not require further purification. The central pyranothiopyranyl cis-fusion was confirmed by 2D NMR NOESY and single-crystal X-ray analysis suggesting that the endo-E-Syn transition state would be the most favored pathway of the reaction. Many heterocycles of this new series were found active against six bacterial and two fungal strains. In addition, all the compounds possess good anti-oxidant activity with the ferric reducing anti-oxidant power value [Formula: see text]. All new structures were docked into active site of angiotensin I converting enzyme (ACE), assuming that the compounds possessed the anti-hypertensive activity potential on the basis of prediction of activity spectra of substances prediction results. Pyranyl ring oxygen in compound 9a forms two hydrogen bonds with HIS353 and HIS513 residues in the active site of the ACE having good G score ([Formula: see text]) of this compound, comparable to that of the reference drug captopril ([Formula: see text]).

An efficient domino reaction in ionic liquid: synthesis and biological evaluation of some pyrano- and thiopyrano-fused heterocycles.

An improved domino/Knoevenagel-hetero-Diels-Alder reaction of two new aldehyde substrates; 7-olefinoxy-coumarin-8-carbaldehyde and 2-alkensulfanyl-quinoline-3-carbaldehyde, with pyrazolones was studied in ionic liquid triethylammonium acetate (TEAA), affording a series of pyrazolopyran annulated-pyrano-fused coumarins, and thiopyrano-fused quinolones. Besides acting as catalyst, since no additional catalyst used, the ionic liquid TEAA also promised its easy recovery. In all new polyheterocycles, the cis-fusion of two pyranyl rings had been inferred from 2D NMR COSY and NOESY experiments. All are good antitubercular agents, as they are found active against Mycobacterium tuberculosis H37Rv, and antibacterial agents, as they are found active against three Gram-positive (Streptococcus pneumoniae, Clostridium tetani, Bacillus subtilis) and three Gram-negative (Salmonella typhi, Vibrio cholerae, Escherichia coli) bacteria.

An improved microwave assisted one-pot synthesis, and biological investigations of some novel aryldiazenyl chromeno fused pyrrolidines.

An improved microwave assisted one-pot method for the synthesis of twelve new aryldiazenylchromeno [4,3-b] pyrrolidines via intramolecular azomethine ylide cycloaddition route is described. The method is efficient and advantageous over conventional and solvent-free thermal methods. The stereochemistry of the compounds was confirmed on the basis of various NMR experiments, and finally by single crystal X-ray diffraction data. N-Methyl or ethyl pyrrolidine based heterocycles gave good biological activities.

An efficient one-pot synthesis, structure, antimicrobial and antioxidant investigations of some novel quinolyldibenzo[b,e][1,4]diazepinones.

A highly improved one-pot procedure for the synthesis of diazepinones, which incorporate a bioactive quinoline nucleus, under catalyst-, and solvent-free environment has been developed. The method allowed us to achieve the products in high yields without requiring a chromatographic separation. All new quinolyldibenzo[b,e][1,4]diazepinones 6a-h thus obtained were further treated to achieve N10-allylated products 7a-h by a simple allylation. The structure of all new synthesized compounds was established based on elemental analysis, mass, (1)H NMR, (13)C NMR, IR spectral data, 2D NMR experiments, and single crystal X-ray study. From in vitro antimicrobial activity studies it revealed all are active against Gram positive (Streptococcus pneumoniae, Clostridium tetani, and Bacillus subtilis), Gram negative (Salmonella typhi, Vibrio chlolerae and Escherichia coli), M. Tuberculosis H37RV bacteria, and fungus like Candia albicans and Aspergillus fumigatus. All were also found to display good antioxidant activity of a ferric reducing power.