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Resveratrol, a natural compound known especially for its antioxidant properties and protective action, opens the door for both it and its structural derivatives to be considered not only as chemopreventive but also as cancer chemotherapeutic agents. Due to the pharmacokinetic problems of resveratrol that demonstrate its poor bioavailability, the study of new derivatives is of interest. Thus, in this work (E)-stilbenes derived directly from resveratrol and other cyclic analogues containing the benzofuran or indole nucleus have been synthesized. The synthesized compounds have been evaluated for their ability to affect tumor growth in vitro. Compounds 2 , 3 , 4 and 5 have shown cytotoxicity in human colon cancer (HT-29) and human pancreatic adenocarcinoma cells (MIA PaCa-2) higher than those of (E)- resveratrol. The indolic derivative 13 , a cyclic analog of resveratrol, has shown in vitro cytotoxic activity 8 times higher than resveratrol against HT-29 cancer cells. The cyclic derivatives 8 , 9 and 12 showed a high inhibition of cell growth in HCT-116 (KRas mutant) at 20 μM, while 13 shows moderate antiangiogenesis activity at 10 μM. [Display omitted] • A series of resveratrol derivatives has been synthesized. • Compounds 2 , 3 , 4 , 5, 8, 9, 10 and 13 have greater cytotoxicity than resveratrol. • 8 and 9 show better neuroprotective effect than resveratrol. • Resveratrol derivatives present a multi-target profile. [ABSTRACT FROM AUTHOR]

Conformationally restricted cyclic analogues of angiotensin II (ANG II), Asp-Arg-Val-Tyr-Val-His-Pro-Phe, with a link between positions 3 and 5 have considerable biological activity. It is proposed that the spatial arrangement of the pharmacophore groups of Tyr, His and Phe side chains and the C-terminal carboxyl group in ANG II and active analogues is similar. Conformational analysis of ANG II and two cyclic analogues c[Sar, Lys,Glu]ANG II and c[Sar,Hcy,Mpt]ANG II was performed, and a geometrical comparison of the low-energy conformations of these compounds allowed one to propose a model of receptor-bound conformation in terms of the spatial arrangement of the pharmacophore groups. This model is characterised by the close spatial location of the His-Phe side chains and the Tyr C-terminal carboxyl group and is stabilised by the electrostatic interaction of Arg and the C-terminal carboxyl group. [ABSTRACT FROM AUTHOR]

Two novel opioid analogues have been designed by substituting the native d-Ala residues in position 2,2' of biphalin with two residues of d-penicillamine or l-penicillamine and by forming a disulfide bond between the thiol groups. The so-obtained compound 9 containing d-penicillamines showed excellent μ/δ mixed receptor affinities (K i (δ) = 5.2 nM; K i (μ) = 1.9 nM), together with an efficacious capacity to trigger the second messenger and a very good in vivo antinociceptive activity, whereas product 10 was scarcely active. An explanation of the two different pharmacological behaviors of products 9 and 10 was found by studying their conformational properties.