TY - JOUR
T1 - Synthesis, cytotoxic activity, DNA topoisomerase-II inhibition, molecular modeling and structure-activity relationship of 9-anilinothiazolo[5,4-b]quinoline derivatives
AU - Loza-Mejía, Marco A.
AU - Olvera-Vázquez, Susana
AU - Maldonado-Hernández, Karina
AU - Guadarrama-Salgado, Teresita
AU - González-Sánchez, Ignacio
AU - Rodríguez-Hernández, Fernando
AU - Solano, José D.
AU - Rodríguez-Sotres, Rogelio
AU - Lira-Rocha, Alfonso
N1 - Funding Information:
We thank Maricela Gutiérrez, Rosa Isela del Villar, Victor M. Arroyo, Georgina Duarte and Margarita Guzmán for determination of all spectra and Nayeli López for elemental analysis. M. A. L.-M. wishes to thank Consejo Nacional de Ciencia y Tecnología (CONACYT-Mexico) for a scholarship for his doctorate studies. We also thank DGAPA-UNAM for financing project PAPIIT IN202805 as well as Facultad de Química for financial support (PAIP 6390-10, 6290-09).
PY - 2009/5/1
Y1 - 2009/5/1
N2 - Some novel 9-anilinothiazolo[5,4-b]quinoline derivatives were synthesized and their cytotoxic activities were examined. The inhibition of some of the most active compounds over human topoisomerase II (Topo II) activity was assessed with the kDNA decatenation assay. The novel compounds differ in the substituents attached to the anilino ring, a dialkylamino alkylamino group, a saturated heterocyclic moiety, a methylthio group at position 2 and a fluorine atom present or absent at 7-position. According to the data, compounds with a diethylaminopropylamino group and a chlorine atom at 4′-position of the anilino ring were the most cytotoxic. The molecular models of all compounds indicated a correlation between hydrophobicity and cytotoxic activity although the direction and magnitude of the dipole moment also had a significant influence on its cytotoxicity. The 2-dialkylaminoalkylamino substituent is flexible and is known to facilitate the crossing of cell membranes; thus, this last barrier may be a limiting step in the mechanisms mediating the cytotoxicity. On the other hand, the activity of 2-methylthio derivatives seems to rely more on the electronic effects brought about by the substitution of the aniline ring. The synthesis, cytotoxicity against cancer cell lines, in vitro inhibition of human topoisomerase II, molecular modeling and the preliminary analysis of structure-activity relationships are presented.
AB - Some novel 9-anilinothiazolo[5,4-b]quinoline derivatives were synthesized and their cytotoxic activities were examined. The inhibition of some of the most active compounds over human topoisomerase II (Topo II) activity was assessed with the kDNA decatenation assay. The novel compounds differ in the substituents attached to the anilino ring, a dialkylamino alkylamino group, a saturated heterocyclic moiety, a methylthio group at position 2 and a fluorine atom present or absent at 7-position. According to the data, compounds with a diethylaminopropylamino group and a chlorine atom at 4′-position of the anilino ring were the most cytotoxic. The molecular models of all compounds indicated a correlation between hydrophobicity and cytotoxic activity although the direction and magnitude of the dipole moment also had a significant influence on its cytotoxicity. The 2-dialkylaminoalkylamino substituent is flexible and is known to facilitate the crossing of cell membranes; thus, this last barrier may be a limiting step in the mechanisms mediating the cytotoxicity. On the other hand, the activity of 2-methylthio derivatives seems to rely more on the electronic effects brought about by the substitution of the aniline ring. The synthesis, cytotoxicity against cancer cell lines, in vitro inhibition of human topoisomerase II, molecular modeling and the preliminary analysis of structure-activity relationships are presented.
KW - Cytotoxic activity
KW - DNA topoisomerase-II inhibition
KW - Molecular modeling
KW - Structure-activity relationship
KW - Thiazolo[5,4-b]quinoline
UR - http://www.scopus.com/inward/record.url?scp=65349127031&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2009.03.052
DO - 10.1016/j.bmc.2009.03.052
M3 - Artículo
SN - 0968-0896
VL - 17
SP - 3266
EP - 3277
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 9
ER -