Loop Diuretics: An Overview of Its History and Evolution.

The loop of Henle plays a key role in kidney function, especially in retaining solutes and concentrating urine. Diuretic agents, crucial for managing fluid overload and related conditions like hypertension and heart failure (HF), enhance water and electrolyte excretion. The history of diuretics dates back to 1775 with the discovery of Digitalis, evolving significantly with the introduction of chlorothiazide in 1957, which revolutionized diuretic therapy. Loop diuretics, developed in the 1950s and including drugs like torsemide, furosemide, and ethacrynic acid, are potent agents acting on the loop of Henle. They are vital for treating severe fluid overload conditions and require careful monitoring to manage potential side effects.

Asymmetric synthesis of the highly methylated tryptophan portion of the hemiasterlin tripeptides.

[reaction: see text] The asymmetric synthesis of the methylated tryptophan portion of hemiasterlin peptides is described. The key reactions are a SnCl4-mediated ring opening of epoxynitriles or epoxysulfones by N-methylindole followed by an asymmetric Strecker reaction. A second approach involving opening of glycidic esters by indoles is also described.

Castleman's Disease, a Case report.

INTRODUCTION: Castleman's disease is a rare lymphoproliferative disorder which may be confused with other causes of lymphadenopathy. CASE REPORT: Here we report a case of unicentric Castleman's disease presenting with cervical lymphadenopathy. The patient was treated with complete surgical excision of lesion and was disease free at the time of reporting this article. This case has been reported for its rarity. CONCLUSION: Though castleman's disease is a relatively rare entity it should be strongly considered in the differential diagnosis of cervical lymphadenopathy.

Triaminotriazine DNA helicase inhibitors with antibacterial activity.

Screening of a chemical library in a DNA helicase assay involving the Pseudomonas aeruginosa DnaB helicase provided a triaminotriazine inhibitor with good antibacterial activity but associated cytotoxicity toward mammalian cells. Synthesis of analogs provided a few inhibitors that retained antibacterial activity and demonstrated a significant reduction in cytotoxicity. The impact of serum and initial investigations toward a mode of action highlight several features of this class of compounds as antibacterials.

Novel non-nucleobase inhibitors of Staphylococcus aureus DNA polymerase IIIC.

The preparation and biological evaluation of 5-substituted-6-hydroxy-2-(anilino)pyrimidinones as a new class of DNA polymerase IIIC inhibitors, required for the replication of chromosomal DNA in Gram-positive bacteria, are described. These new dGTP competitive inhibitors displayed good levels of in vitro inhibition and antibacterial activity against Staphylococcus aureus. A new class of dATP competitive inhibitors, 6-substituted-2-amino-5-alkyl-pyrimidin-4-ones, whose antibacterial activity was unaffected by serum, were identified.

A new class of small molecule RNA polymerase inhibitors with activity against rifampicin-resistant Staphylococcus aureus.

The RNA polymerase holoenzyme is a proven target for antibacterial agents. A high-throughput screening program based on this enzyme from Staphylococcus aureus had previously identified a 2-ureidothiophene-3-carboxylate as a low micromolar inhibitor. An investigation of the relationships between the structures of this class of compounds and their inhibitory- and antibacterial activities is described here, leading to a set of potent RNA polymerase inhibitors with antibacterial activity. Characterization of this bioactivity, including studies of the mechanism of action, is provided, highlighting the power of the reverse chemical genetics approach in providing tools to inhibit the bacterial RNA polymerase.