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Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes

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Neural Regeneration Research 2013年第24期8卷 2290-2302页

作者： Farfán-García Eunice Dalet trujillo-ferrara josé guadalupe Castillo-Hernández María del Carmen Guerra-Araiza Christian Humberto Soriano-Ursúa Marvin Antonio Escuela Superior de Medicina Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón s/n Col. Casco de Santo Tomas

In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.

关键词： neural regeneration G-Protein coupled receptors structural biology drug design neurodegenera-tive disorders , oligomedzation biased signaling Parkinson's disease Alzheimer's disease dopa-mine receptors muscarinic receptors grants-supported paper neuroregeneration

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Scope of translational medicine in developing boroncontaining compounds for therapeutics

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World Journal of Translational Medicine 2017年第1期6卷 1-9页

作者： Ana Karen García-ávila Eunice Dalet Farfán-García Juan Alberto Guevara-Salazar josé guadalupe trujillo-ferrara Marvin Antonio Soriano-Ursúa Department of Biochemistry and Section of Post Graduate Studies and Research Escuela Superior de MedicinaInstituto Politécnico Nacional Department of Physiology and Section of Post Graduate Studies and Research Escuela Superior de MedicinaInstituto Politécnico Nacional

The ubiquitousness of naturally occurring boron-containing compounds(BCCs) has led to their constant contact with ***,many synthetic BCCs have been elaborated for a broad spectrum of purposes,especially boric,boronic and borinic *** BCCs were once employed primarily as antiseptics and later as antibiotics,they have become an increasingly relevant therapeutic ***,this potential of BCCs has been drastically limited due to some unfortunate intra-hospital accidents in the 1940 s and 1950 *** increasing use of BCCs as insecticides,antimicrobials,and other agents is providing new insights into their role in the physiology of several living species and in the pathophysiology of *** is becoming clear that BCCs act through a wide range of mechanisms,as do their corresponding boron-free *** comparing BCCs and similar boron-free compounds,in many cases the former show advantages in the medical *** current minireview focuses on how BCCs have been developed by means of translational medicine,a process connecting biomedical research with clinical *** process of discovery is currently in an exponential stage.

关键词： Boron Boron-containing compounds Drug development Toxicity Medicinal chemistry Pharmacology

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