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, 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

Study of reactivity of cyanoacetohydrazonoethyl-<i>N</i>-ethyl-<i>N</i>-methyl benzenesulfonamide: preparation of novel anticancer and antimicrobial active heterocyclic benzenesulfonamide derivatives and their molecular docking against dihydrofolate reductase

<p>This article describes the synthesis of some novel heterocyclic sulfonamides having biologically active thiophene <b>3</b>, <b>4</b>, <b>5</b>, <b>6</b>, coumarin <b>8</b>, benzocoumarin <b>9</b>, thiazole <b>7</b>, piperidine <b>10</b>, pyrrolidine <b>11</b>, pyrazole <b>14</b> and pyridine <b>12</b>, <b>13</b>. Starting with 4-(1-(2-(2-cyanoacetyl)hydrazono)ethyl)-N-ethyl-N-methylbenzenesulfonamide <b>(2)</b>, which was prepared from condensation of acetophenone derivative <b>1</b> with 2-cyanoacetohydrazide. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR and MS spectral data. All the newly synthesized heterocyclic sulfonamides were evaluated as <i>in-vitro</i> anti-breast cancer cell line (MCF7) and as <i>in-vitro</i> antimicrobial agents. Compounds <b>8</b>, <b>5</b> and <b>11</b> were more active than MTX reference drug and compounds <b>12</b>, <b>7</b>, <b>4</b>, <b>14</b>, <b>5</b> and <b>8</b> were highly potent against <i>Klebsiella pneumonia</i>. Molecular operating environment performed virtual screening using molecular docking studies of the synthesized compounds. The results indicated that some prepared compounds are suitable inhibitor against dihydrofolate reductase (DHFR) enzyme (PDBSD:4DFR) with further modification.</p