Plant regeneration from cocoyam callus derived from shoot tips and petioles

The effects of various growth regulators on morphogenesis from cocoyam tissues (Xanthosoma sagittifolium) were investigated. Calluses were initiated from shoot tip and petiole explants and proliferated on medium containing 1.36 μM dicamba. Callus production was significantly greater from petioles than from shoot tips. Thidiazuron (0.045 μM) enhanced callus production when dicamba (13.5 μM) was used, and was more favorable to petioles than shoot tips. Friable shoot tip callus was subcultured into liquid media containing either 1.36 μM dicamba alone, 1.35 μM 2,4-D + 0.46 μM kinetin or 1.36 μM dicamba + 0.46 μM kinetin to induce adventive regeneration. Tissues producing single or aggregated shoot buds were subcultured into media containing 0, 0.049 and 0.49 μM 2-isopentenyladenine where bud multiplication and shoot regeneration were observed. Bud aggregates were formed from callus in liquid cultures containing 1.36 μM dicamba, 1.36 μM dicamba + 0.46 μM kinetin or 1.35 μM 2,4-D + 0.46 μM kinetin. Shoot bud clumps which remained green produced shoots, daughter buds, and plantlets in stationary and agitated liquid media containing 0, 0.049 and 0.49 μM 2iP. This revised version was published online in June 2006 with corrections to the Cover Date.     

Rapid hit to lead evaluation of pyrazolo[3,4-d]pyrimidin-4-one as selective and orally bioavailable mGluR1 antagonists

Our HTS effort yielded a preferential mGluR1 pyrimidinone antagonist 1 with lead-like characteristics. Rapid hit to lead (HTL) study identified compounds with improved functional activity and selectivity such as 1b with little improvements in ADME properties. Addition of an aminosulfonyl group on the N-1 aromatic ring led to 2f, a compound with similar in vitro biochemical profiles as those of 1b but drastically improved in vitro ADME properties. These improvements were paralleled by rat PK study characterized by low clearance and quantitative bioavailability. Compound 2f represented a true lead-like molecule that is amenable for further lead optimization (LO) evaluation.