C-Geranylated flavonoids from Paulownia tomentosa fruits with antimicrobial potential and synergistic activity with antibiotics

0463702 - ÚOCHB 2017 RIV GB eng J - Journal Article
Navrátilová, A. - Nešuta, Ondřej - Vančatová, I. - Čížek, A. - Varela-M, R. E. - López-Abán, J. - Villa-Pulgarin, J. A. - Mollinedo, F. - Muro, A. - Žemličková, H. - Kadlecová, D. - Šmejkal, K.
C-Geranylated flavonoids from Paulownia tomentosa fruits with antimicrobial potential and synergistic activity with antibiotics.
Pharmaceutical Biology. Roč. 54, č. 8 (2016), s. 1398-1407. ISSN 1388-0209. E-ISSN 1744-5116
Institutional support: RVO:61388963
Keywords : flavonoid * geranyl * Leishmania * MRSA * synergy
Subject RIV: FR - Pharmacology ; Medidal Chemistry
Impact factor: 1.916, year: 2016

C-6-Geranylated flavonoids possess promising biological activities. These substances could be a source of lead compounds for the development of therapeutics. The study was designed to evaluate their antibacterial and antileishmanial activity. C-6-Geranylated flavanones were tested in micromolar concentrations against promastigote forms of Leishmaniabrazilensis, L. donovani, L. infantum, and L. panamensis against methicillin-resistant Staphylococcus aureus (MRSA); and synergistic potential with antibiotics was analyzed. IC50 values (after 72h) were calculated and compared with that of miltefosine. Flow cytometry and DNA fragmentation analysis were used the mechanism of the effect. Geranylated flavanones or epigallocatechin gallate were combined with oxacillin, tetracycline, and ciprofloxacin, and the effects of these two-component combinations were evaluated. Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were established (after 24h), the synergy was measured by the checkerboard titration technique, and the sums of the fractional inhibitory concentrations (Sigma FICs) were computed. 3-O-Methyl-5-O-methyldiplacone and 3-O-methyldiplacone showed good antileishmanial activities (IC50 8-42M). 3-O-Methyl-5-hydroxydiplacone activates the apoptotic death at leishmanias, the effect of 3-O-methyl-5-O-methyldiplacone has another mechanism. The test of the antibacterial activity showed good effects of 3-O-methyldiplacol and mimulone against MRSA (MIC 2-16g/mL), and in six cases, the results showed synergistic effects when combined with oxacillin. Synergistic effects were also found for the combination of epigallocatechin gallate with tetracycline or oxacillin. This work demonstrates anti-MRSA and antileishmanial potential of geranylated flavanones and uncovers their promising synergistic activities with antibiotics. In addition, the mechanism of antileishmanial effect is proposed.
Permanent Link: http://hdl.handle.net/11104/0262809