Ana Estévez-Braun

Inhibitory effects of lapachol derivatives on epstein-barr virus activation.

Sixteen derivatives (2-17) synthesized from the naphthoquinone lapachol (1), were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. They exhibited a variety of inhibitory activities from very high to moderate, which allow us to suggest structure-activity relationships. Ten of these derivatives are reported for the first time, their structures being thoroughly determined by spectroscopic methods.

Structure and absolute configuration of triterpene dimers from Maytenus scutioides

Abstract Eight new triterpene dimers ( 1–8 ) were isolated from Maytenus scutioides (Celastraceae). Their structures were determined on the basis of spectroscopic evidence and their absolute configurations by means of CD studies. Their possible biogenetic route is discussed. One unnatural dimer was synthesized by a hetero Diels-Alder reaction.

Bioactive Montanine Derivatives from Halide-induced Rearrangements of Haemanthamine-type Alkaloids. Absolute Configuration by VCD

An unexpected rearrangement of haemanthamine-type alkaloids in the presence of halogenating agents has been found. Rearranged compounds present the 5,11-methanomorphantridine framework characteristic of montanine-type alkaloids. These compounds are difficult to obtain because of their scarcity in natural sources and because the synthetic approaches developed so far require numerous steps. Vibrational circular dichroism (VCD) spectroscopy was used to determine the absolute configuration of one of the rearranged compounds. Several rearranged alkaloids showed antimalarial activity.

Pancratium canariense as an Important Source of Amaryllidaceae Alkaloids

Four new alkaloids (1-4) have been isolated from a methanolic extract of bulbs of Pancratium canariense, together with 12 known alkaloids (5-16). The structures of the new alkaloids were determined by extensive 1D and 2D NMR spectroscopic studies and X-ray diffraction.

Synthesis and Anti-HIV Activity of Lupane and Olean-18-ene Derivatives. Absolute Configuration of 19,20-Epoxylupanes by VCD

Lupane triterpenoids 2 and 5-12 and oleanene derivatives 13 and 14 were prepared from lupeol (1), betulin (3), and germanicol (4). They were tested for anti-HIV activity, and some structure-activity relationships were outlined. The 20-(S) absolute configuration of epoxylupenone (8) was assessed by comparison of the observed and DFT-calculated vibrational circular dichroism spectra. The CompareVOA algorithm was employed to support the C-20 configuration assignment. The 20,29 double bond in lupenone (2) and 3-epilupeol (15) was stereoselectively epoxidized to produce 20-(S)-8 and 20-(S)-16, respectively, an assignment in agreement with their X-ray diffraction structures.

Electronic and Cytotoxic Properties of 2-Amino-naphtho[2,3-b]furan-4,9-diones

The electronic properties of a new set of cytotoxic 2-amino-naphtho[2,3-b]furan-4,9-dione derivatives (1-8) are evaluated. The electron delocalization of these compounds is described by means of their redox potentials and solvatochromic properties. The large solvatochromism of their intramolecular electron transfer band is analyzed using the linear solvation energy relationship method. In addition, this method determined the importance of the molecular environment, quantifying the interactions that compounds (1-8) establish with their surrounding media, with the capacity of acting as hydrogen-bond acceptors (HBA) and hydrogen-bond donors (HBD) and the dipolarity/polarizability being the most significant ones. As a result, a relationship between the electronic and the cytotoxic properties of these compounds is proposed.

Three lignans from Bupleurum salicifolium

Abstract Three new lignans, 2β-hydroxy-2α-3′,4′-dimethoxybenzyl-3α-3″,4″-methylenedioxybenzyl-γ-butyrolactone, 2β-acetyl-2α-3′,4′-dimethoxybenzyl-3α-3″,4″-methylenedioxybenzyl-γ-butyrolactone and 3′,4′-dimethoxybenzyl-3-3″,4″-methylenedioxybenzyl-2,3-dehydro-γ-butyrolactone, were isolated from the leaves of Bupleurum salicifolium . Three other lignans were identified as 2β-3′,4′-dimethoxybenzyl-3α-3″,4″-methylene-dioxybenzyl-γ-butyrolactone, 2β,3α-bis(3′,4′-dimethoxybenzyl)-γ-butyrolactone and 1-3′,4′-dimethoxyphenyl-2,3-naphthalide-γ-butyrolactone. The triterpene betulin was also obtained.

Synthesis and cytotoxic activity of metallic complexes of lawsone

In the present study, a series of metallic complexes of the 1,4-naphthoquinone lawsone (2-6) were synthesized and evaluated for potential cytotoxicity in a mouse leukemic macrophagic RAW 264.7 cell line. Cell viability was determined by the MTT assay. Significant growth inhibition was observed for the copper complex (4) with an IC(50) value of 2.5 μM. This compound was selected for further evaluation of cytotoxic activity on several human cancer cells including HT-29 (human colorectal adenocarcinoma), HepG2 (human hepatocellular carcinoma) and HeLa, (human cervical adenocarcinoma cells). Significant cell viability decrease was also observed in HepG2 cells. The apoptotic potential of this complex was evaluated in these cells. Compound 4 induced apoptosis by a mechanism that involves the activation of caspases 3, 8 and 9 and modulation of apoptotic-related proteins such as Bax, Bad, and p53. These results indicate that metal complexes of lawsone derivatives, in particular compound 4, might be used for the design of new antitumoral agents.

Multicomponent Synthesis of Antibacterial Dihydropyridin and Dihydropyran Embelin Derivatives

A series of dihydropyran and dihydropyridin embelin derivatives were synthesized through a novel and straightforward one-pot protocol based on a three-component reaction with embelin, aldehydes, and cyclic enaminones as synthetic imputs. The type of substituent on the nitrogen atom of the β-enaminone is key to obtain nitrogenated or oxygenated rings. The obtained compounds were active against Gram-positive bacteria, including multiresistant Staphylococcus aureus clinical isolates.

Synthesis and study of antiproliferative, antitopoisomerase II, DNA-intercalating and DNA-damaging activities of arylnaphthalimides

A series of arylnaphthalimides were designed and synthesized to overcome the dose-limiting cytotoxicity of N-acetylated metabolites arising from amonafide, the prototypical antitumour naphthalimide whose biomedical properties have been related to its ability to intercalate the DNA and poison the enzyme Topoisomerase II. Thus, these arylnaphthalimides were first evaluated for their antiproliferative activity against two tumour cell lines and for their antitopoisomerase II in vitro activities, together with their ability to intercalate the DNA in vitro and also through docking modelization. Then, the well-known DNA damage response in Saccharomyces cerevisiae was employed to critically evaluate whether these novel compounds can damage the DNA in vivo. By performing all these assays we conclude that the 5-arylsubstituted naphthalimides not only keep but also improve amonafides biological activities.