Microwave assisted synthesis of 2-amino-6-methoxy-4H-benzo[h]chromene derivatives

A convenient and efficient method using microwave assisted synthesis of 4H-benzo[h]chromenes (7 and 8), by the reaction of 4-methoxy-1-naphthol (1) with a mixture of aromatic aldehydes (2) and malononitrile (3) or ethyl cyanoacetate (5) and also, by the reaction of 4-methoxy-1-naphthol (1) with α-cyanocinnamonitriles (4) or ethyl α-cyanocinnamates (6) in ethanolic piperidine solution was examined. Structures of the newly synthesized compounds were established on the basis of spectral data, IR, 1H NMR, 13C NMR, 13C NMR-DEPT and MS data

Synthesis, reactions and biological evaluation of benzyltriazolophthalazine derivatives

A series of triazolophthalazine derivatives (4-22) were synthesized and characterized. The structures of the newly synthesized compounds were confirmed by spectral data. The newly synthesized compounds were also screened for their antimicrobial activity

Ethyl 2-amino-4-(4-fluoro­phen­yl)-6-meth­oxy-4H-benzo[h]chromene-3-carboxyl­ate

In the title compound, C23H20FNO4, the fluoro-substituted benzene ring is approximately perpendicular to the mean plane of the 4H-benzo[h]chromene ring system [maximum deviation = 0.264 (1) Å], with a dihedral angle of 83.79 (6)°. The pyran ring adopts a flattened boat conformation. The meth­oxy group is slightly twisted from the attached benzene ring of the 4H-benzo[h]chromene moiety [C—O—C—C = −2.1 (2)°]. An intra­molecular N—H⋯O hydrogen bond generates an S(6) ring motif. In the crystal, mol­ecules are linked by N—H⋯O and N—H⋯F hydrogen bonds into a layer parallel to the bc plane. The crystal packing also features C—H⋯π inter­actions

Synthesis, Reactions and Antimicrobial Activities of 8-Ethoxycoumarin Derivatives

Condensation of 3-acetyl-8-ethoxycoumarin (3) with thiosemicarbazide gave ethylidenehydrazinecarbothioamide 5, which was transformed into the thiazolidin-4-one derivatives 6,7. Interaction of 3 with DMF/POCl3 gave b-chloroacroline derivative 8. Treatment of 3 with malononitrile gave benzo[c]chromone and 2-aminobenzonitrile derivatives 9 and 10, respectively with respect to the reaction conditions. Condensation of 3-(2-bromoacetyl)-8-ethoxycoumarin (4) with o-phenylenediamine gave 3-(quioxaline-2-yl)-8-ethoxycoumarin hydrobromide (11), while 4 reacted with 2-aminopyridine to give chromenopyridopyrimidine derivative 12. Condensation of 4 with potassium thio-cyanate/methanol gave an unexpected derivative, 2H-chromeno-3-carboxy(methyl-carbonimidic)thioanhydride 16, which upon treatment with (NH2)2·H2O gave 3-ethoxy-2-hydroxybenzaldehyde azine 19. Interaction of 4 with thiourea derivatives gave thiazole derivatives 20a–c. The structures of the newly synthesized compounds were confirmed by their spectra data. The newly synthesized compounds were also screened for their antimicrobial activity

Synthesis, biological activity and molecular modeling study of new Schiff bases incorporated with indole moiety

Halawa AH, Abd El-Gilil SM, Bedair AH, et al. Synthesis, biological activity and molecular modeling study of new Schiff bases incorporated with indole moiety. Zeitschrift für Naturforschung C. 2017;72(11-12):467-475.A new series of heterocyclic Schiff bases 2-9 containing indole moiety were synthesized by facile and efficient condensation of indole-3/2/5-carboxaldehyde (1a/1b/1c) with different aromatic and heterocyclic primary amines using conventional and/or microwave irradiation methods. The structures of the obtained compounds were assigned by sophisticated spectroscopic and spectrometric techniques (1D-NMR, 2D-NMR and MS). The synthesized compounds were screened for their cytotoxicity and antibacterial activities. In vitro cytotoxicity screening revealed that compound 5 exhibited moderate activity against KB-3-1 cell line (IC50 = 57.7 mu M) while 5-indolylimino derivative 7 indicated close to the activity (IC50 = 19.6 mu M) in comparison with the positive control (+)-Griseofulvin (IC50 = 19.2 mu M), while the tested compounds 5, 6b, 7 and 9 revealed good or moderate antibacterial activity. In addition, molecular docking study of Schiff bases 2-9 was performed by Molecular Operating Environment (MOE 2014.09) program on the matrix metalloproteinase-8 (MMP-8) (Protein Data Bank (PDB) ID: 1MNC) in an attempt to explore their mode of action as anticancer drugs

Synthesis and biological activities of new bis-indole derivatives via microwave irradiation

Halawa AH, Bedair AH, El-Agrody AM, et al. Synthesis and biological activities of new bis-indole derivatives via microwave irradiation. Zeitschrift für Naturforschung B. 2017;72(9):639-646.Three new series of bis-indole derivatives were synthesized based on p-phenylenediamine (2-4, 5 and 6) and 4,4'-ethylenedianiline moieties (7-9) using facile and efficient condensation of three positional isomeric indole-carboxaldehyde derivatives (1a-c) with bifunctional amines upon microwave irradiation. The symmetric dimeric indole derivatives 2-4 as well as non-symmetric analogues 5 and 6 were obtained by in situ condensation of the respective positional 3-, 2- and 5-isomeric indole-carboxaldehydes with p-phenylenediamine, while compounds 7-9 resulted from respective condensation based on 4,4'-ethylenedianiline. Structures of the obtained compounds were deduced by advanced spectroscopic methods (H-1 NMR, C-13 NMR and MS). In agar diffusion assay, derivative 6 showed moderate antibacterial activity against various Gram positive and negative bacteria, while derivative 7 displayed moderate activity against several Gram positive bacteria. However, in Resazurin assay employing the human cervix carcinoma cell line (KB-3-1), derivatives 2-9 turned out to be inactive

Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: cytotoxicity and molecular docking investigations

Halawa AH, Abd El-Gilil SM, Bedair AH, et al. Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: cytotoxicity and molecular docking investigations. MEDICINAL CHEMISTRY RESEARCH. 2018;27(3):796-806.New amide linked bis-indoles 10a, b, and 12 have been synthesized by treatment of tryptamine (9) or 5-aminoindole (11) with oxalyl chloride or adipoyl chloride. In addition, a newly indole derivatives 14-16 incorporated or fused with coumarin moieties have been prepared through the reaction of 9 or 11 with 4-chloro-3-formylcoumarin (13a) or 4-chloro-3-nitrocoumarin (13b). Further, 13-(3-nitrophenyl)-6,13-dihydrochromeno[4,3-b]pyrrolo[3,2-f]quinolin-12(3H)-one (20) has been produced via one-pot Mannish reaction of 11, 4-hydroxycoumarin (17), and 3-nitrobenzaldehyde (18) in the presence of N-chlorosuccinimide (NCS) as a catalyst. A mixture of 3-[(3H-indol-3-ylidene)methyl]-4-hydroxy-2H-chromen-2-one (24A), and 3-[(1H-indol-3-yl)methylene]chroman-2,4-dione (24B) has been obtained with ratio 1:1 through Knoevenagel condensation reaction of indole-3-carboxaldehyde (21) and 17. Structures of the obtained compounds have been assigned by sophisticated spectroscopic techniques (H-1-NMR, C-13-NMR, and 2D NMR) and mass spectrometry. All the synthesized compounds have been screened for their cytotoxic activity against the human cervix carcinoma cell line (KB-3-1), where compounds 14a, 16, and 20 exhibit the highest potent activity (IC50 = 1.8, 2.2, and 7.9 A mu M, respectively) in comparison with the positive control (+)-Griseofulvin (IC50 = 19.2 A mu M), whereas the tautomeric mixture 24A, B show moderate activity (IC50 = 71.3 A mu M). Moreover, molecular docking study of the synthesized compounds toward the matrix metalloproteinase-8 (MMP-8) (PDB ID: 1MNC) has also discussed

Synthesis, in vitro cytotoxicity activity against the human cervix carcinoma cell line and in silico computational predictions of new 4-arylamino-3-nitrocoumarin analogues

Halawa AH, Eliwa EM, Hassan AA, et al. Synthesis, in vitro cytotoxicity activity against the human cervix carcinoma cell line and in silico computational predictions of new 4-arylamino-3-nitrocoumarin analogues. JOURNAL OF MOLECULAR STRUCTURE. 2020;1200: UNSP 127047.A new series of 4-arylamino-3-nitrocoumarin analogues (4-18) have been synthesized and characterized by sophisticated spectroscopic techniques (H-1 NMR, C-13 NMR) and mass spectrometry. All the new synthesized compounds were evaluated for their in vitro cytotoxic activity against the human cervix carcinoma cell line (KB-3-1) using resazurin assay with (+)-griseofulvin as the positive control (IC50 = 19 mu M). Among them, thiazolidinylidene derivative 17a that bearing malononitrile unit displayed the best cytotoxic potency with IC50 value of 21 mu M. Also, in silico docking simulation studies were conducted on human DNA topoisomerase 1 (Top1) (PDB: 1T8I) to explore and interpret the interaction pattern between the selected compounds and target enzyme as well confirm the acquired cytotoxicity results. In addition to the above, in silico predictions of physicochemical properties, ADME (absorption, distribution, metabolism and excretion) parameters, oral toxicity and indication of toxicity targets were implemented for some title compounds. (C) 2019 Published by Elsevier B.V