Molecular Design of Bivalent or Dual Action Drugs

CNU IR > Pharmacy and Science > 2011 Taiwanese-Russian Organic, Medicinal and Bio Chemistry Interactions & PST Medicinal Chemistry Symposium > Item 310902800/24201

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Title:	Molecular Design of Bivalent or Dual Action Drugs
Authors:	N. S. Zefirov V. A.Palyulin O. N. Zefirova
Date:	2011
Issue Date:	2011-06-23 14:56:57 (UTC+8)
Abstract:	Design of new drugs is a sophisticated process involving the application of molecular modeling and QSAR techniques, virtual screening and molecular docking. The joint application of these approaches provides deeper understanding of both structure-activity relationships and ligand-receptor interactions as well as facilitates lead finding and optimization. For the above discussed design the molecular models of all closed and open forms of metabotropic (mGluR1-8) and ionotropic (NMDA andd AMPA) glutamate receptors, adenosine, melatonin, GABAA and GABAc receptors and tubulin have been either built or refined. The docking of known agonists, antagonists, modulators, and channel blockers into the models was used to reveal binding modes of ligands and to explain known structure-activity relationships. Dual action of a drug can be sub-classified into (1) its action on two different biotargets and (2) action on two different sites of the same biotarget. The first case will be exemplified by our design of new neuroprotective compounds. The second will be exemplified by our design of new neuroprotective compounds. The second case will be clarified using (a) the bivalent positive modulator of AMPA receptor and (b) dual action conjugate of colchicine with a "simplified" taxol analogue interacting with tubulin. This approach was successfully used in the design of new neuroprotectors with cognition enhancing properties (extraordinary high potency of some designed compounds starting from picomolar concentration had been revealed - absolute record among all currently known positive AMPA receptor modulators) as well as for synthesis of dual action compounds active against human lung carcinoma A549 cell line.
Relation:	2011年台俄有機、藥物與生物化學交流暨藥物化學研討會，起迄日：2011/04/06~2011/04/05，地點：溪頭台大實驗林
Appears in Collections:	[Pharmacy and Science] 2011 Taiwanese-Russian Organic, Medicinal and Bio Chemistry Interactions & PST Medicinal Chemistry Symposium

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