- PHENOL DERIVATIVES FOR USE AS ANTIMICROBIAL, ANTIBACTERIAL, BACTERICIDE
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Phenol derivatives of general formula (I) and (II), wherein meanings of the substituents are indicated in the description, their pharmaceutically acceptable salts, together with the processes for their preparation, their use as antimicrobial, antibacterial, bactericide agents and the corresponding pharmaceutical compositions are disclosed.
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Page/Page column 36
(2020/09/19)
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- Influence of the adamantyl moiety on the activity of biphenylacrylohydroxamic acid-based HDAC inhibitors
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To investigate the influence of the adamantyl group on the biological properties of known HDAC inhibitors with a 4-phenylcinnamic skeleton, a series of compounds having the adamantyl moiety in the cap structure were synthesized and compared to the corresponding hydroxamic acids lacking this group. An unexpected finding was the substantial reduction of inhibitory activity toward the tested enzymes, in particular HDAC6, following the introduction of the adamantyl group. In spite of the reduced ability to function as HDAC inhibitors, the compounds containing the adamantyl moiety still retained a good efficacy as antiproliferative and proapoptotic agents. A selected compound (2c; ST3056) of this series exhibited an appreciable antitumor activity against the colon carcinoma xenograft HCT116.
- Cincinelli, Raffaella,Musso, Loana,Giannini, Giuseppe,Zuco, Valentina,De Cesare, Michelandrea,Zunino, Franco,Dallavalle, Sabrina
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supporting information
p. 251 - 259
(2014/05/06)
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- Synthesis and structure-activity relationships of new antiproliferative and proapoptotic retinoid-related biphenyl-4-yl-acrylic acids
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Atypical retinoids, or retinoid-related molecules (RRMs), represent a class of proapoptotic agents with a promising potential in the treatment of neoplastic diseases. In the present work, the synthesis and structure-activity relationship of a series of 3′-adamantan-1-yl-biphenyl-4-yl-acrylic acids substituted in ring A were studied. The synthesized compounds were evaluated for their antiproliferative activity in a human promyelocitic leukemia cell line (NB4), and in an ovarian carcinoma cell system including IGROV-1, carrying a functional wild-type p53, and a cisplatin-resistant subline, IGROV-1/Pt-1. The presence of at least one oxygenated substituent in positions 4′ or 5′ appears determinant for the antiproliferative activity. With two substituents of this kind the activity increases, particularly in the case of alkylenedioxy compounds. The activation of DNA damage response as indicated by phosphorylation of H2AX histone, RPA-2 protein, and p53 at serine 15 by the most apoptotic compounds provides additional support to the hypothesis that the genotoxic stress is a critical event mediating apoptosis induction by compounds of this group.
- Cincinelli, Raffaella,Dallavalle, Sabrina,Nannei, Raffaella,Merlini, Lucio,Penco, Sergio,Giannini, Giuseppe,Pisano, Claudio,Vesci, Loredana,Ferrara, Fabiana Fosca,Zuco, Valentina,Zanchi, Chiara,Zunino, Franco
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p. 4863 - 4875
(2008/03/15)
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- Synthesis and structure-activity relationships of a new series of retinoid-related biphenyl-4-ylacrylic acids endowed with antiproliferative and proapoptotic activity
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Atypical retinoids (AR) represent a class of proapoptotic agents with promising potential in the treatment of neoplastic diseases. In the present work 4′-hydroxybiphenyl-4-ylacrylic acids were studied as a novel series of AR. The synthesized compounds were evaluated for their antiproliferative activity in a human promyelocytic leukemia cell line (NB4) and in an ovarian carcinoma cell system including IGROV-1, carrying a functional wild-type p53, and a cisplatin-resistant subline, IGROV-1/Pt-1. The presence of a bulky lipophilic group at position 3′ (adamantan-1-yl being the best) and the E configuration of the acrylic moiety appear essential for activity below 1 μM. No substitution on the rings or on the double bond improved the activity. A qualitative correlation between the log P and molecular volume of the 3′-substituent and the antiproliferative activity was found. From the study of a few selected compounds, it appears that the presence of the carboxylic group is an essential requirement for apoptogenic properties but not for antiproliferative activity, this being maintained in amide derivatives. On the other hand, compounds able to induce apoptosis produced a detectable level of genotoxic damage. This observation supports the hypothesis that the genotoxic stress is a critical event mediating apoptosis induction by compounds of this class. Among the compounds investigated, E-3-(3′-adamantan-1-yl-4′- hydroxybiphenyl-4-yl)acrylic acid (2) was chosen for further investigation.
- Cincinelli, Raffaella,Dallavalle, Sabrina,Nannei, Raffaella,Carella, Serena,De Zani, Daniele,Merlini, Lucio,Penco, Sergio,Garattini, Enrico,Giannini, Giuseppe,Pisano, Claudio,Vesci, Loredana,Carminati, Paolo,Zuco, Valentina,Zanchi, Chiara,Zunino, Franco
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p. 4931 - 4946
(2007/10/03)
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- A novel atypical retinoid endowed with proapoptotic and antitumor activity
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The novel atypical retinoid E-3-(4′-hydroxy-3′-adamantylbiphenyl-4-yl)acrylic acid (ST1926, 4) exhibited a potent antiproliferative activity on a large panel of human tumor cells. Despite almost complete loss of ability to activate RARs, the compound was an effective apoptosis inducer and surprisingly produced DNA damage, that likely contributes to the proapoptotic activity. Following oral administration, 4 was well tolerated and caused tumor growth inhibition in the ovarian carcinoma, A2780/DX, and in the human melanoma, MeWo, growing in nude mice, thus supporting the therapeutic interest of the novel agent.
- Cincinelli, Raffaella,Dallavalle, Sabrina,Merlini, Lucio,Penco, Sergio,Pisano, Claudio,Carminati, Paolo,Giannini, Giuseppe,Vesci, Loredana,Gaetano, Carlo,Illy, Barbara,Zuco, Valentina,Supino, Rosanna,Zunino, Franco
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p. 909 - 912
(2007/10/03)
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