Visible Light-Mediated Decarboxylation Rearrangement Cascade of ω-Aryl- N-(acyloxy)phthalimides.

A Smiles-type radical rearrangement induced by visible-light-mediated decarboxylation of ω-aryl- N-(acyloxy)phthalimides was developed, giving rise to pharmacologically important substance classes: phenylethylamine derivatives, dihydroisoquinolinones, and benzoazepinones were synthesized on the basis of readily available benzoic acids or benzaldehydes and ß- or γ-amino acids. This methodology facilitates the synthesis of enantiopure D-amphetamine and of precursors of capsazepinoid bronchodilators.

Antitubercular and Cytotoxic Chlorinated seco-Cyclohexenes from Uvaria alba.

Two new chlorine-containing polyoxygenated seco-cyclohexenes, albanols A (1) and B (2), along with the oxepinone metabolite grandiuvarone (3) were isolated from the endemic Philippine Annonaceae plant Uvaria alba. Both new compounds exhibited modest antitubercular activity. Compound 1 showed cytostatic activity (ranging from 1-50 µM) against HeLa cells and weak antiproliferative activity against HUVEC and K-562 cells with GI50 values of 106 and 81 µM, respectively.

Antitubercular and cytotoxic polyoxygenated cyclohexane derivatives from Uvaria grandiflora.

Chromatographic purification of the DCM sub-extract of Uvaria grandiflora led to the isolation and characterization of a new polyoxygenated cyclohexane derivative, grandifloranol (1), together with five known compounds. Among the compounds isolated, zeylenone (3) showed moderate antitubercular activity against Mycobacterium tuberculosis H37Rv with MIC90 value of 51.2 µM and antiproliferative or cytotoxic activity against human myeloid leukaemia (K-562) and HeLa cells with IC50 values of 2.3 and 18.3 µM, respectively.

Antibacterial and COX-2 Inhibitory Tetrahydrobisbenzylisoquinoline Alkaloids from the Philippine Medicinal Plant Phaeanthus ophthalmicus.

Phaeanthus ophthalmicus (Roxb. ex G.Don) J.Sinclair (previously known as P. ebracteolatus (Presl) Merr) is a Philippine medicinal plant occurring as evergreen shrub in the lowland forests of Luzon islands. It is used traditionally by Filipinos to treat bacterial conjunctivitis, ulcer and wound infections. Based on previous investigations where cyclooxygenase-2 (COX-2) functions as immune-linked factor in infectious sensitivities to bacterial pathogens by triggering pro-inflammatory immune-associated reactions, we investigated the antimicrobial and COX inhibitory activities of the extracts and tetrahydrobisbenzylisoquinoline alkaloids of P. ophthalmicus in vitro and in silico to validate its ethnomedicinal uses. Thus, the dichloromethane-methanol (DCM-MeOH) crude extract and alkaloid extracts exhibiting antibacterial activities against drug-resistant bacterial strains such as methicillin-resistance Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Klebsiella pneumoniae + CRE and Pseudomonas aeruginosa + MBL afforded (+)-tetrandrine (1) and (+)-limacusine (2) as the major biologically active tetrahydrobisbenzylisoquinoline alkaloidal constituents after purification. Both tetrahydrobisbenzylisoquinoline alkaloids 1 and 2 showed broad spectrum antibacterial activity with strongest inhibition against the Gram-negative bacteria MßL-Pseudomonas aeruginosa Klebsiella pneumoniae + CRE. Interestingly, the alkaloid limacusine (2) showed selective inhibition against ovine COX-2 in vitro. These results were ascertained by molecular docking and molecular dynamics simulation experiments where alkaloid 2 showed strong affinity in the catalytic sites of Gram-negative bacterial enzymes P. aeruginosa elastase and K. pneumoniae KPC-2 carbapenemase (enzymes involved in infectivity mechanisms), and of ovine COX-2. Overall, our study provides credence on the ethnomedicinal use of the Philippine medicinal plant P. ophthalmicus as traditional plant-based adjuvant to treat bacterial conjunctivitis and other related infections. The antibacterial activities and selective COX-2 inhibition observed for limacusine (2) point to its role as the biologically active constituent of P. ophthalmicus. A limited number of drugs with COX-2 inhibitory properties like celecoxib also confer antibacterial activity. Thus, tetrahydrobisbenzyl alkaloids, especially 2, are promising pharmaceutical inspirations for developing treatments of bacterial/inflammation-related infections.