ABSTRACT
A novel monoraphid diatom species, Cocconeiscrisscrossis You, Yu, Kociolek & Wang, sp. nov. is examined and described from the Qingyi River and Maolan Nature Reserve of southern China. The morphological description is based on light microscopy and scanning electron microscopy observations and the new species is compared with similar taxa in this genus. The characteristics unique to Cocconeiscrisscrossissp. nov. include its central area extending irregularly to both sides, it having closed valvocopulae with heavily silicified fimbriate margins and poles of the valvocopulae have 'sword-shaped' siliceous extensions. These features differentiate this new species from others in the genus. This new species was found in alkaline waterbodies, including streams, waterfall and ponds. It was usually found as an epiphyte on the stones; however, it was present on other substrates such as mosses.
ABSTRACT
This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.
Subject(s)
Antineoplastic Agents/chemical synthesis , Benzazepines/chemical synthesis , Cell Cycle Proteins/antagonists & inhibitors , Lactams/chemical synthesis , Protein Serine-Threonine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , Thiones/chemical synthesis , Administration, Oral , Animals , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Benzazepines/pharmacokinetics , Benzazepines/pharmacology , Biological Availability , Cell Line, Tumor , Cell Survival/drug effects , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Humans , Lactams/pharmacokinetics , Lactams/pharmacology , Mice , Mice, Nude , Mitosis , Models, Molecular , Neoplasm Transplantation , Protein Conformation , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship , Thiones/pharmacokinetics , Thiones/pharmacology , Transplantation, Heterologous , Polo-Like Kinase 1ABSTRACT
Preparative chemical methods for the synthesis of eight oxidative transformation products of ethinyl estradiol (EE) and norethindrone acetate (NA) are described. The prepared materials are useful as reference materials and standards for pharmaceutical analysis of EE and NA as bulk chemical or in formulated product. All eight products result from oxidation of the A and/or B rings of the parent compounds. Oxidation of the heteroannular 3,5 dienyl acetate derivative of NA resulted in the 6 alpha-hydroxy, 6 beta-hydroxy and 6-keto NA. Oxidation of 6-keto NA led to the preparation of 6 alpha-hydroxy, 6 beta-hydroxy, 6-keto- and Delta(6) EE. Delta(11) EE was prepared from estrone.
