title: Toxicogenomic analysis of pharmacological active coumarins isolated from Calophyllum brasiliense.
abstract: Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree, mainly distributed in South and Central America. It is an important source of bioactive natural products like, for instance soulatrolide, and mammea type coumarins. Soulatrolide is a tetracyclic dipyranocoumarins and a potent inhibitor of HIV-1 reverse transcriptase and Mycobacterium tuberculosis. Mammea A/BA and A/BB coumarins, pure or as a mixture, are highly active against several leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. In the present work, a toxicogenomic analysis of Soulatrolide and Mammea A/BA + A/BB (3:1) mixture was performed in order to validate the toxicological potential of this type of compounds. Soulatrolide or mixture of mammea A/BA + A/BB (3:1) was administered orally to male mice (CD-1) at dose of 100 mg/kg/daily, for 1 week. After this time, mice were sacrificed, and RNA extracted from the liver of treated animals. Transcriptomic analysis was performed using Affymetrix Mouse Gene 1.0 ST Array. Robust microarray analysis (RMA) and two way ANOVA test revealed for mammea mixture treatment 46 genes upregulated and 72 downregulated genes; meanwhile, for soulatrolide 665 were upregulated and 1077 downregulated genes. Enrichment analysis for such genes revealed that in both type of treatments genetic expression were mainly involved in drug metabolism. Overall results indicate a safety profile. The microarray data complies with MIAME guidelines and are deposited in GEO under accession number GSE72755.
authors.affiliation: Instituto de Química, UNAM, Mexico City, Mexico.
authors.forename: J C
authors.initials: JC
authors.lastname: Gomez-Verjan
authors.affiliation: Instituto de Química, UNAM, Mexico City, Mexico.
authors.forename: E A
authors.initials: EA
authors.lastname: Estrella-Parra
authors.affiliation: Instituto de Química, UNAM, Mexico City, Mexico.
authors.forename: I
authors.initials: I
authors.lastname: Gonzalez-Sanchez
authors.affiliation: Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, UNAM, Mexico City, Mexico.
authors.forename: N A
authors.initials: NA
authors.lastname: Rivero-Segura
authors.affiliation: Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, UNAM, Mexico City, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Vazquez-Martinez
authors.affiliation: Lab. Fitofarmacología, Depto. de Farmacología, Facultad de Medicina, UNAM; México City, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: Magos-Guerrero
authors.affiliation: Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, U.S.A.
authors.forename: D
authors.initials: D
authors.lastname: Mendoza-Villanueva
authors.affiliation: Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, UNAM, Mexico City, Mexico.
authors.forename: M A
authors.initials: MA
authors.lastname: Cerbón-Cervantes
authors.affiliation: Instituto de Química, UNAM, Mexico City, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Reyes-Chilpa