Genoprotection by complexation: The case of Phyllanthus orbicularis K extract

• Published in: Computational and theoretical chemistry Vol. 1164; p. 112555
• Main Authors: Castanedo, Lázaro A.M., Sánchez Lamar, Angel, Morera Boado, Cercis, Nuez Veulens, Ania de la, Matta, Chérif F.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.09.2019
• Subjects: 2-amino-1-methyl-6-phenylimidazo; 2–6 di-sec-butylphenol (DSBP); 4-aminobiphenyl (4-ABP); 5-b]pyridine (PhIP); Aromatic amines; Basis set superposition error (BSSE); Genoprotection; m-phenylendiamine (m-PDA); Statistical thermodynamics; m-phenylendiamine (m-PDA); Statistical thermodynamics; Aromatic amines; 2-amino-1-methyl-6-phenylimidazo; 4-aminobiphenyl (4-ABP); 2–6 di-sec-butylphenol (DSBP); Basis set superposition error (BSSE); Genoprotection; 5-b]pyridine (PhIP)
• ISSN: 2210-271X
• DOI: 10.1016/j.comptc.2019.112555

[Display omitted] •Phyllanthus orbicularis K’s extract has anti-mutagenic effects the mechanism of which is elucidated.•Mutagenic amines are shown to be inactivated by one of the phenolic compounds isolated from this plant.•Complexation is proposed as a mode of genoprotective action of the active ingredient(s) in this extract.•Semiempirical, DFT, and statistical mechanical calculations suggest the stability of the mutagen-phytophenol complexes. The aqueous extract of the herb Phyllanthus orbicularis Kunth inhibits the mutagenicity of certain aromatic amines (m-phenylendiamine (m-PDA), 4-aminobiphenyl (4-ABP), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)). Meanwhile, the phenolic compound 2–6 di-sec-butylphenol (DSBP) was isolated from this plant’s extract. Computational evidence is presented to support the possibility of a direct complexation between DSBP and each one of these three amines. This complexation is proposed as a possible mode of genoprotective action of the active ingredient(s) present in this extract. Semiempirical dispersion-corrected PM6-D and dispersion-corrected density functional theory (DFT) calculations, corrected for basis set superposition error (BSSE), and followed by statistical thermodynamics analysis demonstrate that the phenol-amines complexes are stable in the following order of decreasing stability: PhIP > m-PDA > 4-ABP. This complexation between the phenol (protector) and each one of the environmentally hazardous amines may interfere with their metabolic bioactivation preventing their conversion into ultimate mutagens. Results from multiple quantum chemical methods, including statistical mechanical analysis, are consistent which lends stronger support to the mechanism than would occur from any one method alone.