title: Increment of antimycobaterial activity on lichexanthone derivatives.
abstract: A new dihydropyranexanthone derived from the natural xanthone lichexanthone (1) was synthesised and, together with other 18 derivatives including ω-bromo and ω-aminoalkoxylxanthones (containing methyl, ethyl, propyl, tertbutylamino and piperidinyl moieties), were tested against Mycobacterium tuberculosis. Nine ω-aminoalkoxylxanthones showed good antimycobacterial activity, and their in vitro cytotoxicity was determined using VERO cells in order to calculate the selectivity index (SI). One of these nitrogenated xanthone derivatives showed very promising results, with MIC of 2.6 μM and SI of 48. This MIC is comparable to values found in "first and second line" drugs commonly used to treat TB. In order to understand better about this compound, it was evaluated together with two other ones that showed good SI, against resistant clinical strains of M. tuberculosis to verify the existence of cross-resistance. A chemometrical approach was useful to establish a pattern of antitubercular activity among the group of ω-aminoalkoxylxanthones, according to some structural and chemical features.
authors.affiliation: Centro de Ciências Exatas e Tecnologia, Universidade Federal de Mato Grosso do Sul, P. O. Box 549, Campo Grande, MS, Brazil. adilson.beatriz@ufms.br.
authors.forename: Ana Camila
authors.initials: AC
authors.lastname: Micheletti
authors.forename: Neli Kika
authors.initials: NK
authors.lastname: Honda
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Pavan
authors.forename: Clarice Q F
authors.initials: CQ
authors.lastname: Leite
authors.forename: Maria de Fatima Cepa
authors.initials: Mde F
authors.lastname: Matos
authors.forename: Renata Trentin
authors.initials: RT
authors.lastname: Perdomo
authors.forename: Danielle
authors.initials: D
authors.lastname: Bogo
authors.forename: Glaucia Braz
authors.initials: GB
authors.lastname: Alcantara
authors.forename: Adilson
authors.initials: A
authors.lastname: Beatriz
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D014709:Vero Cells; D044004:Xanthones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D044004:Xanthones; C587518:lichexanthone