Pharmacological properties of furoxans and benzofuroxans: recent developments

The chemistry of furoxans (1, 2, 5-oxadiazole-2-oxides) and benzofuroxans (benzo[1, 2-c]1, 2, 5-oxadiazole-1-oxides) is very well known. These systems are widely used in organic chemistry as intermediate compounds for the synthesis of numerous heterocycles. In the other hand, furoxan and benzofuroxan derivatives were extensively studied as bioactive compounds. They possess remarkable biological activities, such as anti-microbial and anti-parasitic properties, mutagenic, immunosuppressive and anticancer effects, anti-aggregating and vasorelaxant activity, among others. In some cases, molecular mode of action was proposed. Recently, the research and development in the medicinal chemistry of these systems have produced hybrid compounds in which furoxan or benzofuroxan moieties together with a classical drug moieties are present in a single molecule. So, new anti-ulcer drugs, calcium channel modulators and vasodilator derivatives were described and they are currently in study. In this presentation recent developments in the medicinal chemistry of furoxans and benzofuroxans will be reviewed.     

Pharmacological properties of some xanthone derivatives

A series of aminoalkanolic derivatives of xanthone were examined in some experimental models of epilepsia, i.e., pilocarpine, aminophylline and pentetrazole-induced seizures. A final objective of this research was to examine the action of these compounds on the central nervous system, namely on spontaneous locomotor activity, amphetamine-induced hyperactivity and narcotic sleep induced by hexobarbital, as well as their influence on the gamma-aminobutyric acid (GABA) level and glutamic acid decarboxylase (GAD) activity in mice brain. The most interesting were the pharmacological results of (R)-2-N-methylamino-1-butanol derivative of 7-chloro-2-methylxanthone [Id], which displayed protective activity against the seizures induced by maximum electroshock and pentetrazole induced seizures; moreover, this compound had a relatively low toxicity and did not exhibit a neurotoxic effect. The influence on the locomotor activity as well as on the amphetamine-induced locomotor hyperactivity in mice was also seen for Id. Compound Id did not decrease the GABA level in mice brain.     

Phytoestrogens: recent developments

Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. Based on their chemical structure, phytoestrogens can be classified into four main groups, i. e., isoflavonoids, flavonoids, stilbenes, and lignans. For each group, the chemistry, dietary sources and biotransformation of the most interesting compounds will be discussed. Since phytoestrogens are structurally very similar to the estrogen 17beta-estradiol, they may exhibit selective estrogen receptor modulating activities. Therefore, special attention will be given to the hormonal effects of various isoflavonoids, including genistein, daidzein, coumestrol and equol, several prenylated flavonoids, especially 8-prenylnaringenin, and the stilbene resveratrol. Furthermore, their non-hormonal effects will be discussed briefly. Finally, the latest developments on the potential protective properties of phytoestrogens and phytoestrogen-containing foods against hormone-dependent breast and prostate cancers and cardiovascular diseases, and as estrogen replacement therapy for postmenopausal women will be discussed.     

Naturally-occurring xanthones: recent developments

A literature survey covering the report of naturally occurring xanthones from January 2000 to December 2004, with 219 references, is presented in this review. Among 515 xanthones reported in this period, 278 were new natural xanthones. These xanthones have been identified from 20 families of higher plants (122 species in 44 genera), fungi (19 species) and lichens (3 species). The structural formulas of 368 identified xanthones, their distribution and a brief mention of their biological properties are also included.     

Pharmacological properties of some aminoalkanolic derivatives of xanthone

A series of appropriate aminoisopropanoloxy derivatives of 2-, 3- or 6-xanthone was synthesized and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure threshold (ScMet) assays and for neurotoxicity (TOX). The most interesting result was the anticonvulsant activity of (+/-)-3-(2-propylamino)-1- [(2-methyl)-6-xanthonoxy]-2-propanol hydrochloride (10), which displayed anti-MES activity with a protective index (TD50/ED50) of 0.80. Some of the obtained compounds were also tested for their effect on the circulatory system (influence on the non-working heart perfusion, protection against adrenaline induced-arrhythmia) and acute toxicity.     

Pharmacological properties of some p-chlorophenoxyacetic acid derivatives]

Among some derivatives of p-chlorophenoxyacetic acid (dialkylaminoethyl, diethylaminoethylmercaptomercaptan and tropine ethers, dialkylaminoethylene amides) there have been discovered compounds with marked neurotropic, locally anesthetic, antiarrhythmic and antihypoxic properties.     

Pharmacological properties of new heterocyclic derivatives of 1,5-benzodiazepine

Sixteen new heterocyclic 1,5-benzodiazepine derivatives (compounds AN8-AN24) were screened for their central action. Compounds AN8-AN10 and AN17 strongly antagonized the action of pentetrazol, compounds AN10, AN14-AN17 and AN22 had potent antiserotonin properties, and compounds AN10, AN19, AN20 and AN23 markedly potentiated the action of DOPA.