[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade, but no tuberculosis-specific drugs have been discovered in 40 years. We identified a diarylquinoline, R207910, that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro (minimum inhibitory concentration 0.06 μg/ml). In mice, R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit. Substitution of drugs included in the World Health Organization's first-line tuberculosis treatment regimen (rifampin, isoniazid, and pyrazinamide) with R207910 accelerated bactericidal activity, leading to complete culture conversion after 2 months of treatment in some combinations. A single dose of R207910 inhibited mycobacterial growth for 1 week. Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers. Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate (ATP) synthase.

https://science.sciencemag.org/content/sci/307/5707/223.full.pdf

A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis.

G protein-coupled, seven-transmembrane segment receptors (GPCRs or 7TM receptors), with more than 1000 different members, comprise the largest superfamily of proteins in the body. Since the cloning of the first receptors more than a decade ago, extensive experimental work has uncovered multiple aspects of their function and challenged many traditional paradigms. However, it is only recently that we are beginning to gain insight into some of the most fundamental questions in the molecular function of this class of receptors. How can, for example, so many chemically diverse hormones, neurotransmitters, and other signaling molecules activate receptors believed to share a similar overall tertiary structure? What is the nature of the physical changes linking agonist binding to receptor activation and subsequent transduction of the signal to the associated G protein on the cytoplasmic side of the membrane and to other putative signaling pathways? The goal of the present review is to specifically address these questions as well as to depict the current awareness about GPCR structure-function relationships in general. (Endocrine Reviews 21: 90 ‐113, 2000)

/pdf/uncovering-molecular-mechanisms-involved-in-activation-of-g-1ah0sdoqbc.pdf

Uncovering Molecular Mechanisms Involved in Activation of G Protein-Coupled Receptors

Quinolines and structurally related heterocycles as antimalarials

Antimalarials from nature

Tuberculosis (TB) is one of the most devastating diseases primarily due to several decades of neglect, and presents a global health threat of escalating proportions. TB is the second leading infectious cause of mortality today behind only HIV/AIDS. The impetus for developing new structural classes of anti-tuberculosis drugs comes from the emergence of multi-drug resistant (MDR) strains to commonly used drugs, substantially longer durations of therapy that are needed as a result of resistance, and the resurgence of disease in immuno - compromised patients. Recent years have witnessed emergence of many new structural classes of anti-TB agents, which have exhibited promising activities against drug-sensitive and drug-resistant strains of the causative organism Mycobacterium tuberculosis. These analogs ideally should decrease the overall duration of therapy with improved efficacy, and exhibit mechanisms of action different from those of existing drugs to counter the resistant strains of M. tuberculosis. This review provides a comprehensive literature compilation on advances in the new structural classes of anti-TB analogs reported during the past five years. Our discussion and observations are concentrated on chemotherapeutic potential of alphabetically listed twenty-seven new structural classes of anti-tuberculosis agents that include:- acetamides, 5-arylidene-2-thiohydantoins, benzoxazoles and benzothiazoles, benzoic acid hydrazones, benzoxazines, carbohydrates, chalcones, coumarins, deazapteridines, imidazoles, indoloquinazolinones, isothiosemicarbazones, mycobactins, 1,8- naphthyridines, phenazines, purines, pyridines, N-pyridinylsalicylamides, pyrimidines and thymidines, pyrroles, quinolines, quinoxalines, terpenes, thiadiazine thiones, thiolactomycines, toludines, and triazoles.

Rahul Jain

Papers

Quinolines and structurally related heterocycles as antimalarials

Antimalarials from nature

Recent advances in new structural classes of anti-tuberculosis agents.

Synthesis, anti-tuberculosis activity, and 3D-QSAR study of 4-(adamantan-1-yl)-2-substituted quinolines.

Ring-substituted quinolines as potential anti-tuberculosis agents.