Letters in Drug Design & Discovery - Volume 8, Issue 6, 2011

We report the synthesis and evaluation of a novel PPARδ agonist, compound 12a, characterized by a benzisoxazole ring. Compound 12a exhibited a potent human PPARδ transactivation activity (EC50: 0.011 μM). Preliminary biological testing suggests that compound 12a has significant HDL-cholesterol elevating effect in an animal model of dyslipidemia.

In order to investigate the SAR of Ezetimibe analogs for cholesterol absorption inhibitions, amide group and electron-deficient pyridine ring were introduced to the C-(3) carbon chain of Ezetimibe. Eight new derivatives of the 2- azetidinone cholesterol absorption inhibitors have been synthesized, and all of them were enantiomerically pure. All the new compounds were evaluated for their activity to inhibit cholesterol a Read More

Quantitative structure activity relationship approach using enhanced replacement method for variable selection was applied to a series of imidazole containing tetrahydrobenzodiazepines as inhibitors of farnesyltransferase. For the purpose the dataset was divided into training set of 31 compounds and test set of 5 compounds using k means clustering. Statistically significant equations were obtained with high correlation Read More

We report the results of the evaluation of a series of imidazole-based compounds against the enzyme 17α- hydroxylase/17,20-lyase (P-45017α). The results show that the compounds were, in general, weak inhibitors of P-45017α in comparison to the standard inhibitor ketoconazole (KTZ) - one was, however, found to be more potent than KTZ.

In order to explore structure-activity relationship (SAR) associated with xanthone framework, a series of prenylated xanthone derivatives 2-9 was synthesized from the key building block 1,3,6,8-tetrahydroxyxanthone 1 and evaluated for their in vitro growth inhibitory activities against HeLa and MDA-MB-231 human cancer cell lines. The in vitro evidence indicated that the inhibitory activity was significantly influenced by the positi Read More

Vasopressin receptor antagonists (vaptans) are a new class of drugs to treat congestive heart failure. Since there are three subtypes of the receptor located in different tissues, it is important to devise tailor-made vaptans to target the appropriate receptor subtype. The binding of three vaptans, OPC21268, mozavaptan and tolvapatan was measured to the human V1-vascular vasopressin receptor (hV1R). Whereas argini Read More

Zerumbonoquinone 10 and zerumbonaminone 11 have been designed to release toxic moieties selectively and preferentially under reductive conditions. These compounds were synthesized by coupling the quinone delivery system with zerumbone alcohol 8 and amine 9. All compounds were evaluated for cytotoxicity against KB (non reductase overexpressing cells), NCI-H187 and MCF-7 (reductase overexpressing cells) a Read More

2,4-Disubstituted pyrroles were polycondensed and tested for lipid-lowering effects in mice. Fluoro-substituted pyrrole monomers and polymers lowered total serum cholesterol by 30-35% and LDL-cholesterol by 47-64%. The lipidlowering effects were similar for polymers and their monomers, however, the polymers produced these effects at dosage concentrations 1/8th that of the monomers.

Novel NO-donor-caffeic acid hybrids with antioxidant, nitric oxide release and vasodilator properties were designed and synthesized through a symbiotic approach using caffeic acid and three different NO-donating groups such as nitric ester, 4-hydroxyl-3-phenylfuroxan and 4-hydroxymethyl-3-phenylsulfonylfuroxan. The antioxidant activities of these hybrid products were assessed by DPPH assay and by detecti Read More

Seven novel 6-(1-acetyl-3-(6-substituted-2-oxo-2H-chromen-3-yl)-4,5-dihydro-1H-pyrazol-5-yl)-2-amino-4- substituted-4H-chromene-3-carbonitrile derivatives were synthesized and characterized by 1H NMR and 13C NMR. All of the compounds have been screened for their antibacterial activity. The results show that compounds 4d and 4g displayed significant activity with MIC of 1.562 μg/mL against B. subtilis ATCC 6633 and 1.56 Read More

The synthesis, in vitro evaluation and conformational study of small-size peptides acting as antifungal agents are reported. These peptides displayed antifungal activity against human pathogenic strains including Candida albicans and Cryptococcus neoformans. Among the peptides reported here, RQWRRWWQR-NH2 exhibited the strongest activity against Cryptococcus neoformans. Our results allowed us to reduce i Read More

Acid-ester and acid-amide norcantharidin derivatives are prepared using a ‘one-pot’ synthetic procedure utilizing the ThalesNano H-cube™ flow hydrogenator. Traditionally, rapid library generation and reaction scale up of these analogues was limited by the batch wise hydrogenation of 5,6-dehydronorcantharidin. This was resolved with the use of flow chemistry. With no associated scale up issues, a method was devised to p Read More

A series of 19 isonicotinic acid hydrazide derivatives has been synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv using alamar blue susceptibility test. The synthesized compounds inhibit Mycobacterium tuberculosis H37Rv strain with minimum inhibitory concentration ranging from (0.00014-0.01174 mM). Among all synthesized compounds seven derivatives Read More