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STRUCTURAL, VIBRATIONAL, UVEVIS, QUANTUM-CHEMICAL PROPERTIES, MOLECULAR DOCKING AND ANTI-CANCER ACTIVITY STUDY OF ANNOMONTINE AND N-HYDROXYANNOMONTINE B-CARBOLINE ALKALOIDS: A COMBINED EXPERIMENTAL AND DFT APPROACH
Author
Affilliation
Federal University of Amazonas. Department of Chemistry. Manaus, AM, Brasil.
Federal Institute of Science and Technology of Amazonas. Manaus, AM, Brasil.
Federal University of Amazonas. Department of Chemistry. Manaus, AM, Brasil.
Federal University of Amazonas. Department of Chemistry. Manaus, AM, Brasil.
Federal University of Amazonas. Department of Chemistry. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Federal University of Amazonas. Department of Chemistry. Manaus, AM, Brasil.
Federal Institute of Science and Technology of Amazonas. Manaus, AM, Brasil.
Federal University of Amazonas. Department of Chemistry. Manaus, AM, Brasil.
Federal University of Amazonas. Department of Chemistry. Manaus, AM, Brasil.
Federal University of Amazonas. Department of Chemistry. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Federal University of Amazonas. Department of Chemistry. Manaus, AM, Brasil.
Abstract
A theoretical and experimental DFT study of the vibrational, structural and quantum properties of
annomontine (1) and N-hydroxyannomontine (2) alkaloids using the B3LYP exchange-correlation
functional with 6-311G (2d, p) basis set is presented. The theoretical geometry optimization data of
the two structures were compared with the X-ray data of (1) in the associated literature and a conformational
study is presented for both molecules, providing a good comprehension of the conformational
stability. In addition, natural bond orbitals (NBOs), HOMO-LUMO energy gap and mapped molecular
electrostatic potential surface (MEPS) calculations were also performed at the same calculation approach.
The calculated UV spectra agreed well with the measured experimental data, with transitions assigned.
The comparative IR studies confirmed the intramolecular hydrogen bonds of the conformations and the
intermolecular hydrogen bonds of dimeric forms and also revealed several characteristic vibrations for
the structures. Molecular docking studies with DNA Topoisomerase II-DNA complex showed binding free
energies of 11.5 and 10.6 kcal/mol for 2 and 1 respectively, while for amsacrine, used for the treatment
of leukemia, and doxorubicin, used for the treatment of breast cancer, bladder cancer, Kaposi's sarcoma,
and acute lymphocytic leukemia, the presented binding free energies values are 10.0 and 9.9 kcal/mol
respectively, revealing good bind affinities of the tested alkaloids with the complex. In vitro cytotoxicity
assay revealed an expressive antitumor activity of N-hydroxyannomontine against human hepatocellular
carcinoma cell line HepG2.
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