The SOSA (selective optimization of side activities) approach is reviewed. It's an alternative to high-throughput screening for drug discovery

Selective optimization of side activities: another way for drug discovery.

Natural phenolic compounds 1900-2000: a bird's eye view of a century's chemistry.

Microorganisms are indispensable for every aspect of human life, in fact all life on earth, although they cannot be seen by the naked eye. Since time immemorial, every process in the biosphere has been affected by the apparently unending ability of microbes to renovate the world around them. More recently, many discoveries have been made in isolating a special class of microorganisms, mainly fungi but also bacteria, commonly called endophytes, which have been shown to have the natural potential for accumulation of various bioactive metabolites which may directly or indirectly be used as therapeutic agents against a plethora of maladies (Kusari & Spiteller, 2010, 2011). Bioprospecting endophytes have led to exciting possibilities to explore and utilize their potential. Several bioprospecting strategies might be employed in order to discover potent endophytes with desirable traits (Figure 1). These include randomly sampling different plants from any population to isolate the associated endophytes, or first performing a detailed study of an ecosystem in order to determine its features with regard to its natural population of plant species, their relationship with the environment, soil composition, and biogeochemical cycles. Another approach is to evaluate the evolutionary relatedness among groups of plants at a particular sampling site, correlating to species, genus, and populations, through morphological data matrices and molecular sequencing, followed by isolation of endophytes from the desired plants. Traditional medicinal plants are also bioprospected for endophytes, especially for the ones capable of producing one or more of the bioactive secondary metabolites present in the host plants. Finally, the valuable information obtained using the different bioprospecting schemes can be pooled together, comparatively evaluated, and stored for further use applying suitable data mining approaches.

/pdf/metabolomics-of-endophytic-fungi-producing-associated-plant-39jt4a3gjs.pdf

Metabolomics of Endophytic Fungi Producing Associated Plant Secondary Metabolites: Progress, Challenges and Opportunities

Previous data showing that several chloroquine analogues containing an intramolecular hydrogen-bonding motif were potent against multidrug-resistant P. falciparum led to the exploration of the importance of this motif. A series of 116 compounds containing four different alkyl linkers and various aromatic substitutions with hydrogen bond accepting capability was synthesized. The series showed broad potency against the drug-resistant W2 strain of P. falciparum. In particular, a novel series containing variations of the alpha-aminocresol motif gave eight compounds with IC50 values more potent than 5 nM against the W2 strain. Such simple modifications, significantly altering the pKa and sterics of the basic side chain in chloroquine analogues, may prove to be part of a strategy for overcoming the problem of worldwide resistance to affordable antimalarial drugs.

http://derisilab.ucsf.edu/pdfs/Madrid_JMedChem_06.pdf

Incorporation of an Intramolecular Hydrogen-bonding Motif in the Side-Chain of 4-Aminoquinolines Enhances Activity against Drug-Resistant P. falciparum

Advances in the Synthesis of Aryltetralin Lignan Lactones

Compounds Related to Podophyllotoxin. X. Synthesis of Picropodophyllin1

The total synthesis of a series of racemic C-18 functionalized steroids was carried out in a search for novel estrogen-and/or progestin-receptor agonists or antagonists. The target compound 3,18-dihydroxyestra-1,3,5(10)-triene (2), 13-(2-oxopropyl)gona-4-en-3-one (3), 13-(1-hydroxy-1-prop-2-ynyl)gona-4-en-3-one (4a and 4b) and 13-(1-acetoxy-2-oxo-1-propyl)gona-4-en-3-one (5) are position isomers of the highly biologically active estradiol, progesterone, norethindrone, and 17-acetoxyprogesterone, respectively. Nevertheless the synthetic C-18 functionalized steroids 3-5 showed little activity in the Clauberg and anti-Clauberg assays. Compound 2 showed no antagonism in the postcoital assay despite the fact that it exhibited weak but measurable in vitro receptor-binding activity.

Shih Yi Wang

Papers

Compounds Related to Podophyllotoxin. X. Synthesis of Picropodophyllin1

Steroids. 2. Synthesis of C-18 functionalized steroids via the Smith-Hughes route.

Synthesis of a dl-stereoisomer of podophyllic acid1

Synthesis of picropodophyllin1

Steroids. 2. synthesis of c-18 functionalized steroids via the smith-hughes route