Novel medicinal compounds

In the past few deeades there has been a hiatus in the momentum of research and discovery of novel medicinal compounds . This particular trend in drug development perhaps is augmented due to two vital factors, namely first, strict empirical and rational approach to drug design and secondly, high standards of safety and therapeutic efficacy together with tremendous increased costs of research and development and finally the clinical trials. 

In order to identify novel lead compounds with antiviral effects, methanol and aqueous extracts of some medicinal plants in the Zingiberaceae family were screened for inhibition of proteases from human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV) and human cytomegalovirus (HCMV). By bioassay-guided fractionation, eight fiavones were isolated from the black rhizomes of Kaempferia parviflora Wall, ex Baker. The most effective inhibitors, 5-hydroxy-7-methoxyfiavone and 5,7-dimethoxyflavone, inhibited HIV-1 protease, with an inhibitory concentration 50 (IC50) values of 19 0,M. Moreover, 5-hydroxy-3,7-dimethoxyflavone inhibited HCV protease and HCMV protease, with IC50 values of 190 and 250 pM, respectively. 

Many early claims of having prepared simple 1-hydroxyindoles have proved to be unfounded, although the unusually stable l-hydroxy-2-phenylindole was obtained in 1895.1-Hydroxyindole itself polymerizes on attempted isolation, while O-acylation, O-alkylation, or the presence of substituents greatly stabilizes the molecule. One 1-hydroxyindole antibiotic has been identified and is the only 1-hydroxyindole derivative isolated from natural sources so far. In contrast, a substantial number of 1-methoxyindoles occurs in various plants, and some of these may inhibit tumor formation in mammals. The biochemistry of these compounds, which include 1-methoxy-indoles, -indolines and -2-oxindoles, has not been widely investigated and could be a very fruitful area for new research which might well lead to novel medicinal agents and other useful compounds. 

J-20) were identified as having the potential to deliver improved potency over the lead compound 3. These candidates were then used as the basis for a traditional medicinal chemistry investigation and optimization (Scheme 7.5). The overall outcome for this study was the identification of four novel thiol compounds with K 6-17 xM, 10-30-fold more potent than the lead compound 3 with a K of 185 xM. 

This section highlights the most significant applications of pyrroles, indoles, and carbazoles in the areas covered in CHEC-II(1996) <1996CHEC-II(2)207> and in related fields where substantial advances have been made since 1995. While sections on polymers, dyes, drugs, and medicinal compounds deal with novel applications of both old and new compounds, the survey of natural products has been restricted to those new structures that have been discovered during the past decade. 

The present and future efforts of medicinal chemists in the development of novel retinoid compounds are discussed in this section. This body of work should ultimately lead to receptor and receptor subtype-selective agonists and antagonists and novel compounds that block proliferative signaling processes. 

By its nature, a screening approach to lead identification has the potential to identify not only structurally novel lead compounds, but also unexpected modes of action or allosteric inhibition." hi cases for which there is no prior experience with drugging a particular biological target or where the natural ligand is not amenable to rational medicinal chemistry processes, screening may provide the most effective method for lead identification. However, because of the... 

Pharmacophoric model meticulously obtained for auxin i.e., a plant hormone) to evolve ultimately four novel groups of active medicinal compounds by thoroughly screening a conglomerate 3D-database of structures. 

The oceans have long been a source of nutrients, additives, and medicines derived from marine mammals and fish however, this article focuses on some of the potential which is harbored in predominantly microscopic organisms which are now being increasingly studied for novel bioactive compounds and chemicals and may provide a sustainable alternative source for new compounds and processes. 

Ebalunode, J.O. et al. (2009) Structure-based shape pharmacophore modeling for the discovery of novel anesthetic compounds. Bioorganic and Medicinal Chemistry, 17, 5133-5138. 

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