Synthesis and characterization of di-phenyl-tin(IV)-salicyliden-ortho-aminophenols: analysis of in vitro antitumor/antioxidant activities and molecular structures.
The one pot reactions carried among salicylaldehyde 1, ortho-aminophenols 2a-2g, and di-phenyl-tin(IV) oxide 3 led to seven di-phenyl-tin(IV) compounds 4a-4g in good yields (97-83%). All compounds were analyzed by IR, 1H, 13C, 119Sn NMR spectroscopy, mass spectrometry and elemental analyses; furthermore, in the case of compounds 4b, 4c, 4e and 4g by X-ray diffraction. Compounds 4a-4g were tested in vitro against six human tumor cell lines U251, PC-3, K-562, HCT-15, MCF-7 and SKLU-1 to assess their in vitro antitumor activity. The results suggest biological specificity towards U251, MCF-7 and SKLU-1 cells at doses below 2.5 microM, which are lower than cis-platin IC50's in the three cell lines. Since the inhibitory concentration values for the series were alike to Ph(2)SnCl(2) is feasible that only the Ph(2)Sn moiety is responsible for those activities, further experiments are under research. Besides, 4a-4g were tested for their antioxidant efficiency in rat brain homogenate showing that 4g is more active (IC50=3.01 microM) than the flavone quercetin (natural antioxidant, IC50=4.11 microM) on inhibition of thiobarbituric acid reactive substances (TBARS). The TBARS activity (IC50) correlates with the ortho-aminophenol substitutions and a linear combination among sigma Hammett, one bond tin coupling constants and tin chemical shifts against the measured IC(50-TBARS) was found. This correlation gave basis that the implied molecular variables can become trackers for the calculation of TBARS inhibitory concentrations in similar systems. Moreover, there seemed to be an inverse structure-response behavior among activities, since the 4g derivative is the less active compound for cytotoxic assays meanwhile it is the best in antioxidant tests.
Beltrán
Hiram I
HI
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, 04510 Coyoacán, México, DF, Mexico. hbeltran@correo.cua.uam.mx
Damian-Zea
Carlos
C
Hernández-Ortega
Simón
S
Nieto-Camacho
Antonio
A
Ramírez-Apan
Maria Teresa
MT
D000627:Aminophenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000627:Aminophenols; D000970:Antineoplastic Agents; D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D011794:Quercetin; D002945:Cisplatin