Arturo San Feliciano

A Short Review on Cardiotonic Steroids and Their Aminoguanidine Analogues

Concepcion P. Melero*, Manuel Medarde and Arturo San FelicianoDepartamento de Quimica Farmaceutica, Facultad de Farmacia, Campus Miguel de Unamuno, 37007Salamanca, SpainTel.: +34 923 29 45 28, Fax: +34 923 29 45 15, E-mail: medarde@gugu.usal.es*Author to whom correspondence should be addressed.Received: 14 November 1999 / Accepted: 9 December 1999 / Published: 21 January 2000Abstract: A short review on cardiotonic steroids and their analogues is presented. The natu-ral, semisynthetic and synthetic derivatives, as well as their mechanism of action and struc-ture-activity relationships are shown, with a special reference to aminoguanidine deriva-tives.Keywords: Digitalis glycosides analogues, structure-activity relationships, inotropic activ-ity, Na+,K+-ATPase, aminoguanidine analogues.

Synthesis and Antimitotic and Tubulin Interaction Profiles of Novel Pinacol Derivatives of Podophyllotoxins

Several pinacol derivatives of podophyllotoxins bearing different side chains and functions at C-7 were synthesized through reductive cross-coupling of podophyllotoxone and several aldehydes and ketones. While possessing a hydroxylated chain at C-7, the compounds retained their respective hydroxyl group with either the 7α (podo) or 7β (epipodo) configuration. Along with pinacols, some C-7 alkylidene and C-7 alkyl derivatives were also prepared. Cytotoxicities against neoplastic cells followed by cell cycle arrest and cellular microtubule disruption were evaluated and mechanistically characterized through tubulin polymerization inhibition and assays of binding to the colchicine site. Compounds of the epipodopinacol (7β-OH) series behaved similarly to podophyllotoxin in all the assays and proved to be the most potent inhibitors. Significantly, 7α-isopropyl-7-deoxypodophyllotoxin (20), without any hydroxyl function, appeared as a promising lead compound for a novel type of tubulin polymerization inhibitors. Experimental results were in overall agreement with modeling and docking studies performed on representative compounds of each series.

Sesquiterpenoids and phenolics of pulicaria paludosa

Abstract Thirteen sesquiterpenoids of the skeletal types caryophyllane, cadinane, oplopane, eudesmane, allo-aromadendrane and 4-epi-guaiane, were isolated from Pulicaria paludosa. Their structures were established mainly by NMR techniques and chemical transformations. Four of them are new natural products. Three flavonoids and some simple phenolic derivatives were also isolated.

Synthesis and pharmacological activity of diarylindole derivatives. Cytotoxic agents based on combretastatins

Taking into account the structure of Combretastatins, we have synthesized and assayed for cytotoxic activity of new indole derivatives. Two aryl groups are maintained in the cis orientation required for activity by means of an indole moiety built up on less active ketoderivatives used as starting materials.

The distribution of lignanoids in the order coniferae

Lignan distribution in the Coniferae order, which includes six families, has been reviewed from 1967 to 1994. The occurrence of lignanoids in five of the six families of this order has been reported and the predominant lignan type is different for each one.

Preparation and cytotoxicity of podophyllotoxin derivatives lacking the lactone ring

Abstract Several cyclolignans lacking of the lactone moiety can easily be prepared from naturally occurring lignans such as podophyllotoxin and deoxypodophyllotoxin by simple chemical transformations. Their cytotoxicity has been studied in four tumoral cell lines. Most of the compounds show similar effects in all the neoplastic systems tested, except the aldehyde 9 (methyl 9-deoxy-9-oxo-α-apopicropodophyllate) and the hydrazones 16 and 17 which show a highly selective cytotoxicity towards HT-29 human colon carcinoma. Additionally, several molecular modeling studies have been done with aldehyde 9 and the corresponding saturated aldehyde 13 in comparison with podophyllotoxin.

Lignans from Juniperus sabina

Abstract Four new natural products, β-peltatin-B methyl ether, podorhizol acetate, 2′-methoxyepipicropodophyllotoxin and 2′-methoxypicropodophyllotoxin, were isolated from the lignan fraction of a n -hexane extract from the leaves of Juniperus sabina , along with picropodophyllotoxone, epipodophyllotoxin, (+)-dihydrosesamin, podorhizol, anhydropodorhizol, epipicropodophyllotoxin and 2′-methoxypodophyllotoxin.

3-Phenylcoumarins as Inhibitors of HIV-1 Replication

We have synthesized fourteen 3-phenylcoumarin derivatives and evaluated their anti-HIV activity. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase gene as reporter. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Six compounds displayed NF-κB inhibition, four resulted Tat antagonists and three of them showed both activities. Three compounds inhibited HIV replication with IC50 values < 25 µM. The antiviral effect of the 4-hydroxycoumarin derivative 19 correlates with its specific inhibition of Tat functions, while compound 8, 3-(2-chlorophenyl)coumarin, seems to act through a mechanism unrelated to the molecular targets considered in this research.

Lignans from Juniperus thurifera

Abstract The isolation and identification of two new natural lignans, (-)epi-podorhizol and deoxypicropodophyllotoxin, and 12 known lignans from a hexane extract of Juniperus thurifera is described.

Chemical constituents of the bark of Dipteryx alata vogel, an active species against Bothrops jararacussu venom.

The effect of four sub-extracts prepared from the lyophilized hydroalcoholic bark of Dipteryx alata (Leguminosae-Papilionoideae) dissolved in a methanol-water (80:20) mixture through a liquid-liquid partition procedure has been investigated against the neuromuscular blockade of the venom of the snake Bothrops jararacussu. The active CH2Cl2 sub-extract has been extensively analyzed for its chemical constituents, resulting in the isolation of four lupane-type triterpenoids: lupeol (1), lupenone (2), 28-hydroxylup-20(29)-en-3-one (3), betulin (4), nine isoflavonoids: 8-O-methylretusin (5), 7-hydroxy-5,6,4’-trimethoxyisoflavone (6), afrormosin (8), 7-hydroxy-8,3’,4’-trimethoxyisoflavone (9), 7,3’-dihydroxy-8,4’-dimethoxyisoflavone (10), odoratin (11), 7,8,3’-trihydroxy-4’-methoxyisoflavone (13), 7,8,3’-trihydroxy-6,4’-dimethoxyisoflavone (15), dipteryxin (17), one chalcone: isoliquiritigenin (7), one aurone: sulfuretin (14) and three phenolic compounds: vanillic acid (12), vanillin (16), and protocatechuic acid (18). Their chemical structures were elucidated on the basis of spectroscopic analysis, including HRMS, 1D- and 2D-NMR techniques.