- New synthesis of 6[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid and evaluation of the influence of adamantyl group on the DNA binding of a naphthoic retinoid
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6[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid (Adapalene), a synthetic aromatic retinoid specific for RARβ and RARγ receptors, has been prepared utilizing a Pd/C-mediated Suzuki coupling between 6-bromo-2-naphthoic acid and 4-methoxyphenyl boronic acid, followed by introduction of an adamantyl group in the position 3 of the formed 6-(4-methoxyphenyl)-2-naphthoic acid. The interaction of 6-(4-methoxyphenyl)-2- naphthoic acid/ethyl ester and the 3-adamantyl analogs with DNA was studied in aqueous solution at physiological conditions by UV-vis spectroscopy. The calculated binding constants Kligand-DNA ranged between 1.1 × 104 M-1 and 1.1 × 105 M-1, the higher values corresponding to those of the adamantylated compounds. Molecular modeling studies have emphasized that the intercalative binding of adapalene and its derivatives to DNA is mainly stabilized by hydrophobic interactions related to the presence of the adamantyl group.
- Milanese, Alberto,Gorincioi, Elena,Rajabi, Mehdi,Vistoli, Giulio,Santaniello, Enzo
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p. 151 - 158
(2011/11/07)
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- Synthesis of aryl-substituted naphthalene-linked pyrrolobenzodiazepine conjugates as potential anticancer agents with apoptosis-inducing ability
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A library of new aryl-substituted naphthalene C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates with various linker architectures were designed, synthesized, and evaluated for their anticancer activity against a panel of 11 human cancer cell lines. All 32 conjugates show anticancer potential, with some of them exhibiting particularly high activity (0.01-0.19μM). Thermal denaturation studies showed effective DNA binding capacity relative to DC-81. In assays for biological activity relating to cell-cycle distribution, these PBD conjugates induce G0/G1-phase arrest and also cause an increase in the levels of p53 and caspase-9 proteins, followed by apoptotic cell death. One conjugate in particular is the most promising candidate of the series, with the potential to be selected for further studies, either alone or in combination with existing anticancer therapies. Getting into the groove: Pyrrolobenzodiazepine (PBD) conjugates showed an effective ability to bind DNA. They induce G0/G1-phase arrest, enhance the expression levels of p53 and caspase-9, and induce apoptosis. One conjugate stands out as particularly promising; it is a suitable candidate for further study, either alone or in combination with current anticancer therapies.
- Kamal, Ahmed,Reddy, M. Kashi,Ramaiah, M. Janaki,Srikanth,Rajender,Reddy, V. Santosh,Kumar, G. Bharath,Pushpavalli,Bag, Indira,Juvekar, Aarti,Sen, Subrata,Zingde, Surekha M.,Pal-Bhadra, Manika
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experimental part
p. 1665 - 1679
(2012/01/05)
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