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, Eliwa EM, Frese M, Sewald N, Shaaban M, El-Agrody AM (2018)
MEDICINAL CHEMISTRY RESEARCH 27(3): 796-806.

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Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Abstract / Bemerkung
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.
Erscheinungsjahr
Zeitschriftentitel
MEDICINAL CHEMISTRY RESEARCH
Band
27
Ausgabe
3
Seite(n)
796-806
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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.
Halawa, A. H., Abd El-Gilil, S. M., Bedair, A. H., Eliwa, E. M., Frese, M., Sewald, N., Shaaban, M., et al. (2018). Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: cytotoxicity and molecular docking investigations. MEDICINAL CHEMISTRY RESEARCH, 27(3), 796-806. doi:10.1007/s00044-017-2103-7
Halawa, A. H., Abd El-Gilil, S. M., Bedair, A. H., Eliwa, E. M., Frese, M., Sewald, N., Shaaban, M., and El-Agrody, A. M. (2018). Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: cytotoxicity and molecular docking investigations. MEDICINAL CHEMISTRY RESEARCH 27, 796-806.
Halawa, A.H., et al., 2018. Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: cytotoxicity and molecular docking investigations. MEDICINAL CHEMISTRY RESEARCH, 27(3), p 796-806.
A.H. Halawa, et al., “Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: cytotoxicity and molecular docking investigations”, MEDICINAL CHEMISTRY RESEARCH, vol. 27, 2018, pp. 796-806.
Halawa, A.H., Abd El-Gilil, S.M., Bedair, A.H., Eliwa, E.M., Frese, M., Sewald, N., Shaaban, M., El-Agrody, A.M.: Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: cytotoxicity and molecular docking investigations. MEDICINAL CHEMISTRY RESEARCH. 27, 796-806 (2018).
Halawa, Ahmed H., Abd El-Gilil, Shimaa M., Bedair, Ahmed H., Eliwa, Essam M., Frese, Marcel, Sewald, Norbert, Shaaban, Mohamed, and El-Agrody, Ahmed M. “Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: cytotoxicity and molecular docking investigations”. MEDICINAL CHEMISTRY RESEARCH 27.3 (2018): 796-806.