16-membered macrolide lactone derivatives bearing a triazole-functionalized arm at the aglycone C13 position as antibacterial and anticancer agents.
PBN-AR
Instytucja
Instytut Genetyki Człowieka Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
angielski
Czasopismo
ChemMedChem
ISSN
1860-7179
EISSN
1860-7187
Wydawca
WILEY-BLACKWELL
DOI
URL
Rok publikacji
2016
Numer zeszytu
Strony od-do
1886-1891
Numer tomu
11
Identyfikator DOI
Liczba arkuszy
1
Autorzy
(liczba autorów: 9)
Pozostali autorzy
+ 8
Streszczenia
Język
angielski
Treść
A series of new C13-triazole-bridged and C13-ether leucomycin analogues with a reduced aldehyde group were synthesized. Derivatives with the highest antibacterial [MIC values (S. epidermidis, S. pneumoniae): ∼2-4 μg mL(-1) ; 2.55-5.09 μm] and cytotoxic [IC50 values (HeLa, KB, MCF-7, A549, HepG2 cells): ∼1.35-3.70 μm] potencies were those with the best aqueous solubility and bearing a saccharide-triazole arm at the C13 position of the aglycone. These derivatives preferentially bind at the ribosomal tunnel and show the most attractive selectivity indexes [SI; calculated relative to the human dermal fibroblast (HDF) cell line], even higher than that of the reference compound cytarabine. Results of molecular docking studies of this type of macrolide antibiotics at the ribosomal tunnel, together with experimentally determined lipophilicity and aqueous solubility values, as well as biological assay data revealed the importance of the introduced functional group at the aglycone C13 arm to the future design of anticancer and antibacterial drug candidates. Our results clearly indicate that the high antibacterial and anticancer activities of these types of macrolides do not necessarily depend on the presence of the aldehyde group at the aglycone lactone ring.
Inne
System-identifier
PX-57d7c244c2dce1a362654d88
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