Structural determinants involved in the activation and regulation of G protein-coupled receptors: lessons from the alpha1-adrenegic receptor subtypes.

The aim of a large number of studies on G protein-coupled receptors was centered on understanding the structural basis of their main functional properties. Here, we will briefly review the results obtained on the alpha1-adrenergic receptor subtypes belonging to the rhodopsin-like family of receptors. These findings contribute, on the one hand, to further understand the molecular basis of adrenergic transmission and, on the other, to provide some generalities on the structure-functional relationship of G protein-coupled receptors.

Progress on Lamellarins

This review covers recent literature on the lamellarins, a family of marine natural products, and related analogs, encompassing synthetic strategies for total synthesis, structure-activity relationships (SAR), and studies on mechanisms of biological action, namely in the context of antitumor activity. It reviews work published from January 2008 to December 2010.

Compostos de platina em quimioterapia do câncer

The vast majority of clinically used antitumor drugs are either synthetic or natural product based organic compounds. In this review we describe different aspects, such as structure-activity relationships, mechanism of action, clinical uses and possible future prospects, of the platinum antitumor complexes, a distinct class of antitumor agents.

Estratégias para a obtenção de compostos farmacologicamente ativos a partir de plantas medicinais: conceitos sobre modificação estrutural para otimização da atividade

In the present paper we discuss, based in our experience, some experimental procedures which may be employed for isolation of active compounds from medicinal plants. We have also emphasized some insights about the way to obtain more active and selective compounds from natural products through structural modifications oriented for analysis of structure-activity relationships.

Synthesis of angiotensin-converting enzyme (ACE) inhibitors: an important class of antihypertensive drugs

This report outlines the discovery, the design and development of new compounds, and, structure-activity relationships for this drug category. Updated approaches to planned syntheses of new worthy ACE-inhibitors are also exploited.

Peptídeos de conformação restrita induzida pela incorporação de unidades (aza)lactâmicas

Conformational constraint is an approach which can be used to restrict the flexibility of peptide molecules and to provide information on the topographical requirements of receptors. The incorporation of conformationally constrained units in a peptide can lead to peptide analogues that present numerous advantages such as the potentialization of the pharmacological activity and the decrease of enzymatic degradation. This review discusses the peptide analogues containing a lactam or azalactam unit in their sequences. Of particular interest has been the replacement of a dipeptide motif in a peptide that simulates a beta-turn.

Ambergris: perfume e síntese

Rules for the occurence of the ambergris odor is presented and discussed in terms of the relationship between chemical structure and odor. A general overview of the major approaches in the synthesis of Ambrox® , the key ambergris-type compound, is also presented.

Novas estratégias terapêuticas para o tratamento da depressão: uma visão da química medicinal

Depression is a widespread humor disturbance promoted mainly by depletion of biogenic neurotransmitter amines involved in the CNS synapses. Effective drug treatments for depression have been available for more than forty years. Despite its remarkable structural diversity, this paper discuss under the medicinal chemistry point of view, all different classes of "monoamine based" antidepressant drugs, emphasizing the rational design, structure-activity relationships (SAR), biotransformation and physico-chemical properties related with antidepressant activity and molecular mechanism of action.

Esquizofrenia: quarenta anos da hipótese dopaminérgica sob a ótica da Química Medicinal

Schizophrenia is a devastating psychiatric illness that affects 1-2% of the world population and continues as a challenge to neuroscience. In this work, we describe an account about the historical evolution of the dopaminergic hypothesis of schizophrenia discussing, from the medicinal chemistry point of view all different classes of antipsychotic drugs, emphasizing the rational design, structure activity relationships (SAR) and physico-chemical properties related with its molecular mechanism of action.

QSAR: a abordagem de Hansch

The Hansch Analysis, also known by QSAR-2D, is an extremely effective tool in the identification and/or improvement of the pharmacological or toxicological profile of xenobiotics. This article presents the theme didactically and with enough detail to clarify the conceptual basis of Hansch Analysis. Besides, it shows the application of the technique in measuring the influence of physicochemical properties on the biological activity of compounds with pharmacological interest.

Sínteses química e enzimática de peptídeos: princípios básicos e aplicações

This review begins with a brief discussion of the biological importance and chemical features of peptides. A description of the existing synthetic methods follows with emphasis on the basic aspects of the chemical and enzymatic syntheses. Techniques used to purify and characterize the synthesized peptides are also discussed. Finally, a few applications of the final products in chemistry, biochemistry, immunology and medicine are presented, such as identification and quantification of naturally occurring peptides, inspection of structure-activity relationships, therapeutics, development and/or improvement of analytical techniques and search for new vaccines.

Alcalóides pirrolizidínicos em espécies do gênero Senecio

Senecio species contain a large variety of secondary metabolites and many of these plants afford pyrrolizidine alkaloids. This paper is a review of the literature, describing 62 pyrrolizidine alkaloids already isolated in 62 of more than 2000 species of Senecio, distributed worldwide. The structure-activity relationships involving their toxicity are also discussed, since some Senecio species used for medicinal purposes are responsible for causing serious adverse effects.

Importância do metabolismo no planejamento de fármacos

It is widely recognized that pharmacokinetic optimization needs to be addressed early in drug discovery to reduce the high failure rate in bringing drugs to market. Poor absorption, too short duration of action due to high elimination rate, or the presence of active metabolites are examples of properties that can potentially lead to unsuccessful clinical programmes. Here I describe a brief overview of advantages and molecular strategies for improving metabolic and pharmacokinetic properties applied to the discovery of fluconazol, beta-blockers, ritonavir and ezetimibe and to the development of the prodrugs enalapril and bambuterol.

Macrolactamas bioativas e síntese de macrociclos por reação de carbociclização radicalar mediada por hidreto de tri-n-butilestanho

This review presents natural, semi-synthetic and synthetic bioactive macrolactams and their structure-activity relationships when available. For macrolactams in clinical use the advantages and disadvantages in relation to other drugs are presented, and for synthetic macrolactams the method used in the cyclization is showed. Regarding macrocyclic synthesis by the tri-n-butyltin hydride-mediated radicalar carbocyclization reaction the precursor, the reaction conditions, products and yields, mechanism and cyclization mode are discussed.

Derivados oleananos e ursanos e sua importância na descoberta de novos fármacos com atividade antitumoral, anti-inflamatória e antioxidante

Oleanolic and ursolic acids are triterpenes that exist abundantly in the plant kingdom. They show antitumor activity and their cytotoxic activity was already evaluated against a broad range of cell lines. The inhibition of enzymes involved in the metabolism of DNA and the induction of apoptosis are known events that have been related to the antitumour activity of these triterpenes. The antiinflamatory and antioxidant activities also seem to play an important role in their antitumour activity. In this review, it is presented an overview of the importance of the potential antitumour, antiinflamatory and antioxidant activities of these triterpenoid derivatives. Also, we propose a structural-activity relationship to triterpenes containing oleanane or ursane skeleton and their cytotoxic activity.