Hybrids of polypyrrole minor groove binders structurally related to the natural antitumor agent distamycin A and -methylene--butyrolactones with Me, Ph, and 4-substituted Ph groups at the lactone C() position were prepd. and evaluated for in vitro cytotoxic activity against a variety of cancer cell lines. The apoptotic and cytotoxic activities against several tumor cell lines were reported and discussed in terms of their structural differences in relation to both the no. of N-methylpyrrole rings and the type of the alkylating unit tethered to the oligopeptidic frame. For polypyrroles I [R = C(:NH)NH2, n = 2, 3; R = NHC(:NH)NH2, n = 3] the cytotoxicity of the hybrids was much greater than that of the -methylene--butyrolactone units II (R1 = Me, Ph, 4-ClC6H4, 4-PhC6H4; m = 1, 3, 5, 7) alone. Using the human leukemia cell line HL-60, the effects of a selected series of compds. on programmed cell death (apoptosis) were detd. I [R = C(:NH)NH2, n = 2, 3; R = NHC(:NH)NH2, n = 3] induce apoptosis as demonstrated from identification of nuclear changes assocd. with apoptosis using fluorescence microscopy and by DNA laddering on agarose gel electrophoresis. I [R = C(:NH)NH2, n = 2] was the most potent, esp. after a short incubation period. It induced extensive hydrolysis of poly ADP-ribose polymerase (PARP), considered to be a hallmark of apoptosis, which plays a crit. role in chromatin architecture and DNA metab.

Design, synthesis, and biological evaluation of hybrid molecules containing alpha-methylene-gamma-butyrolactones and polypyrrole minor groove binders

BARALDI, Pier Giovanni;AGHAZADEH TABRIZI, Mojgan;ROMAGNOLI, Romeo
2004

Abstract

Hybrids of polypyrrole minor groove binders structurally related to the natural antitumor agent distamycin A and -methylene--butyrolactones with Me, Ph, and 4-substituted Ph groups at the lactone C() position were prepd. and evaluated for in vitro cytotoxic activity against a variety of cancer cell lines. The apoptotic and cytotoxic activities against several tumor cell lines were reported and discussed in terms of their structural differences in relation to both the no. of N-methylpyrrole rings and the type of the alkylating unit tethered to the oligopeptidic frame. For polypyrroles I [R = C(:NH)NH2, n = 2, 3; R = NHC(:NH)NH2, n = 3] the cytotoxicity of the hybrids was much greater than that of the -methylene--butyrolactone units II (R1 = Me, Ph, 4-ClC6H4, 4-PhC6H4; m = 1, 3, 5, 7) alone. Using the human leukemia cell line HL-60, the effects of a selected series of compds. on programmed cell death (apoptosis) were detd. I [R = C(:NH)NH2, n = 2, 3; R = NHC(:NH)NH2, n = 3] induce apoptosis as demonstrated from identification of nuclear changes assocd. with apoptosis using fluorescence microscopy and by DNA laddering on agarose gel electrophoresis. I [R = C(:NH)NH2, n = 2] was the most potent, esp. after a short incubation period. It induced extensive hydrolysis of poly ADP-ribose polymerase (PARP), considered to be a hallmark of apoptosis, which plays a crit. role in chromatin architecture and DNA metab.
2004
Baraldi, Pier Giovanni; Nunez, Md; AGHAZADEH TABRIZI, Mojgan; DE CLERCQ, E; Balzarini, J; Bermejo, J; Estevez, F; Romagnoli, Romeo
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/517050
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 83
  • ???jsp.display-item.citation.isi??? 77
social impact