In vivo effective dibenzo[b,d]furan-1-yl-thiazoles as novel PDE-4 inhibitors.

Herein we report the synthesis, PDE-4B and TNF-α inhibitory activities of a few dibenzo[b,d]furan-1-yl-thiazole derivatives. The hydroxycyclohexanol amide derivatives 14, 18, 24, 29, 31 and 33 exhibited promising in vitro PDE-4B and TNF-α inhibitory activities. Compound 24 showed good systemic availability in preclinical animal models and was also found to be non-toxic (exploratory mutagenicity test).

Quinolone-based HDAC inhibitors.

HDAC inhibitors emerged as promising drug candidates in combating wide variety of cancers. At present, two of the compounds SAHA and Romidepsin were approved by FDA for cutaneous T-cell lymphoma and many are in various clinical phases. A new quinolone cap structure was explored with hydroxamic acid as zinc-binding group (ZBG).

Three new pentacyclic triterpenes and some flavonoids from the fruits of an Indian Ayurvedic plant Dendrophthoe falcata and their estrogen receptor binding activity.

Extensive chromatographic screening of extracts of the fruits of the Indian Ayurvedic plant, Dendrophthoe falcata, resulted in the isolation of three new triterpenes, 3beta-acetoxy-1beta-(2-hydroxy-2-propoxy)-11alpha-hydroxy-olean-12-ene (1), 3beta-acetoxy-11alpha-ethoxy-1beta-hydroxy-olean-12-ene (2) and 3beta-acetoxy-1beta-hydroxy-11alpha-methoxy-olean-12-ene (3) along with nine known compounds, 3beta-acetoxy-1beta,11alpha-dihydroxy-olean-12-ene (4), 3beta-acetoxy-1beta,11alpha-dihydroxy-urs-12-ene (5), 3beta-acetoxy-urs-12-ene-11-one (6), 3beta-acetoxy-lup-20(29)-ene (7), 30-nor-lup-3beta-acetoxy-20-one (8), (20S)-3beta-acetoxy-lupan-29-oic acid (9), kaempferol-3-O-alpha-L-rhamnopyranoside (10), quercetin-3-O-alpha-L-rhamnopyranoside (11), and gallic acid (12). The structures of these compounds were determined using 1D and 2D NMR and high resolution electrospray mass spectrometry. These compounds were assayed for binding to estrogen receptors-alpha and beta and kaempferol-3-O-alpha-L-rhamnopyranoside (10) was found to be a ligand for both receptors with greater affinity for beta.