Animals ; Anti-HIV Agents ; chemistry ; pharmacology ; Furans ; pharmacology ; HIV Integrase Inhibitors ; chemistry ; pharmacology ; HIV-1 ; drug effects ; Humans ; Keto Acids ; chemistry ; pharmacology ; Molecular Structure ; Naphthyridines ; pharmacology ; Triazoles ; pharmacology

BACKGROUND: Antimicrobial susceptibility of Legionella spp. has rarely been studied in Korea. Therefore, we aimed to determine the susceptibility of Legionella spp. to various antibiotics. METHODS: We assessed the antimicrobial susceptibility of 66 environmental and clinical Legionella isolates collected between January 2001 and December 2008 from Korea and Japan. The minimum inhibitory concentrations (MICs) of 6 antibiotics, namely, azithromycin, ciprofloxacin, clarithromycin, clindamycin, gatifloxacin, and gemifloxacin were determined by the broth microdilution method using buffered starch yeast extract broth. RESULTS: The MIC ranges of the 6 antibiotics used against the Legionella isolates were as follows: 0.004-0.062 microgram/mL (azithromycin), 0.002-0.5 microgram/mL (ciprofloxacin), 0.004-0.5 microgram/mL (clarithromycin), 0.12-4 microgram/mL (clindamycin), 0.002-0.12 microgram/mL (gatifloxacin), and 0.008-1 microgram/mL (gemifloxacin). CONCLUSIONS: Legionella spp. isolates from Korea and Japan were most susceptible to gatifloxacin. Azithromycin, clarithromycin, ciprofloxacin, and gemifloxacin were also effective for treating legionellosis.
Anti-Bacterial Agents/*pharmacology ; Azithromycin/pharmacology ; Ciprofloxacin/pharmacology ; Clarithromycin/pharmacology ; Clindamycin/pharmacology ; Drug Resistance, Bacterial ; Fluoroquinolones/pharmacology ; Humans ; Legionella/*drug effects/isolation & purification ; Legionellosis/diagnosis/microbiology ; Microbial Sensitivity Tests ; Naphthyridines/pharmacology

The mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, acts as a "master switch" for cellular anabolic and catabolic processes, regulating the rate of cell growth and proliferation. Dysregulation of the mTOR signaling pathway occurs frequently in a variety of human tumors, and thus, mTOR has emerged as an important target for the design of anticancer agents. mTOR is found in two distinct multiprotein complexes within cells, mTORC1 and mTORC2. These two complexes consist of unique mTOR-interacting proteins and are regulated by different mechanisms. Enormous advances have been made in the development of drugs known as mTOR inhibitors. Rapamycin, the first defined inhibitor of mTOR, showed effectiveness as an anticancer agent in various preclinical models. Rapamycin analogues (rapalogs) with better pharmacologic properties have been developed. However, the clinical success of rapalogs has been limited to a few types of cancer. The discovery that mTORC2 directly phosphorylates Akt, an important survival kinase, adds new insight into the role of mTORC2 in cancer. This novel finding prompted efforts to develop the second generation of mTOR inhibitors that are able to target both mTORC1 and mTORC2. Here, we review the recent advances in the mTOR field and focus specifically on the current development of the second generation of mTOR inhibitors as anticancer agents.
Antineoplastic Agents ; pharmacology ; Cell Proliferation ; drug effects ; Furans ; pharmacology ; Humans ; Imidazoles ; pharmacology ; Indoles ; pharmacology ; Mechanistic Target of Rapamycin Complex 1 ; Mechanistic Target of Rapamycin Complex 2 ; Morpholines ; pharmacology ; Multiprotein Complexes ; antagonists & inhibitors ; Naphthyridines ; pharmacology ; Neoplasms ; pathology ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Purines ; pharmacology ; Pyridines ; pharmacology ; Pyrimidines ; pharmacology ; Quinolines ; pharmacology ; Signal Transduction ; Sirolimus ; pharmacology ; TOR Serine-Threonine Kinases ; antagonists & inhibitors