One-Pot Synthesis of -Fused Quinolone-4 Tetracyclic Scaffolds from 2,2-Disubstituted Indolin-3-ones.

A cascade transformation of C2-quaternary indoxyls leading to an efficient assembly of complex (dihydro)indolo[1,2-]quinolin-5-one ring systems is reported. The method involves the gram-scale preparation of 2-(2-aryl-3-oxoindolin-2-yl)-2-phenylacetonitriles which are then converted with methyl ketones to the corresponding 2-(2-oxo-2-aryl(alkyl)ethyl)-2-phenylindolin-3-ones. The latter can either be isolated with good yields (75-96%) or, in the case of -nitroacetophenone, used for further base-assisted intramolecular SAr cyclization resulting in indoxyl-fused quinolone-4 hybrids (up to 95%).

[Antihypertensive therapy in patients with arterial hypertension and concomitant diseases in real clinical practice (according to the National Registry of Arterial Hypertension, 2019-2022)].

Background: Arterial hypertension (AH) remains the leading risk factor associated with cardiovascular diseases (CVDs), cerebrovascular disease and chronic kidney disease. About 70% of patients with AH who are on monotherapy cannot achieve blood pressure (BP) targets, and therefore all quidelines for the management of AH have recently recommended prescribing combination therapy (PCT). In real clinical practice (RCP), there remains significant uncertainty in the effectiveness and rationality of therapy, despite the wide availability of antihypertensive drugs (AHD) and the presence of recommendations for a stepwise approach to prescribing combinations of specific groups of AHD in different clinical situations.

G-Quadruplex Forming DNA Sequence Context Is Enriched around Points of Somatic Mutations in a Subset of Multiple Myeloma Patients.

Multiple myeloma (MM) is the second most common hematological malignancy, which remains incurable despite recent advances in treatment strategies. Like other forms of cancer, MM is characterized by genomic instability, caused by defects in DNA repair. Along with mutations in DNA repair genes and genotoxic drugs used to treat MM, non-canonical secondary DNA structures (four-stranded G-quadruplex structures) can affect accumulation of somatic mutations and chromosomal abnormalities in the tumor cells of MM patients.

Practical Approaches for the Yeast Genome Modification.

The yeast is a unique genetic object for which a wide range of relatively simple, inexpensive, and non-time-consuming methods have been developed that allow the performing of a wide variety of genome modifications. Among the latter, one can mention point mutations, disruptions and deletions of particular genes and regions of chromosomes, insertion of cassettes for the expression of heterologous genes, targeted chromosomal rearrangements such as translocations and inversions, directed changes in the karyotype (loss or duplication of particular chromosomes, changes in the level of ploidy), mating-type changes, etc. Classical yeast genome manipulations have been advanced with CRISPR/Cas9 technology in recent years that allow for the generation of multiple simultaneous changes in the yeast genome.