Synthesis, Molecular Docking, In Vitro and In Vivo Studies of Novel Dimorpholinoquinazoline-Based Potential Inhibitors of PI3K/Akt/mTOR Pathway.

A (series) range of potential dimorpholinoquinazoline-based inhibitors of the was synthesized. Several compounds exhibited cytotoxicity towards a panel of cancer cell lines in the low and sub-micromolar range. Compound with the highest activity and moderate selectivity towards MCF7 cells which express the mutant type of PI3K was also tested for the ability to inhibit PI3K-(signaling pathway) downstream effectors and associated proteins.

Bioinformatic Analysis of the Nicotinamide Binding Site in Poly(ADP-Ribose) Polymerase Family Proteins.

The PARP family consists of 17 members with diverse functions, including those related to cancer cells' viability. Several PARP inhibitors are of great interest as innovative anticancer drugs, but they have low selectivity towards distinct PARP family members and exert serious adverse effects. We describe a family-wide study of the nicotinamide (NA) binding site, an important functional region in the PARP structure, using comparative bioinformatic analysis and molecular modeling.

Discovery of Novel Tankyrase Inhibitors through Molecular Docking-Based Virtual Screening and Molecular Dynamics Simulation Studies.

Tankyrase enzymes (TNKS), a core part of the canonical Wnt pathway, are a promising target in the search for potential anti-cancer agents. Although several hundreds of the TNKS inhibitors are currently known, identification of their novel chemotypes attracts considerable interest. In this study, the molecular docking and machine learning-based virtual screening techniques combined with the physico-chemical and ADMET (absorption, distribution, metabolism, excretion, toxicity) profile prediction and molecular dynamics simulations were applied to a subset of the ZINC database containing about 1.

[Cardiovascular syphilis (current state of the problem and analysis of own observations)].

A description of two cases of cardiovascular syphilis is presented. The introduction discusses the relevance of visceral syphilis. The literary review is constructed in a chronological format and reflects the stages of studying the problem of cardiovascular syphilis.

[The Experience of Use Triple Antithrombotic Therapy in Patients With Acute Coronary Syndrome and Atrial Fibrillation].

Aim: In real life to evaluate the effectiveness and safety of apixaban with double antiplatelet therapy for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and the recent episode of acute coronary syndrome without ST segment elevation.

Materials And Methods: 8 patients with atrial fibrillation and the recent (8-14 days after the onset of symptoms of ACS) episode of acute coronary syndrome without ST segment elevation were involved into the research. The effectiveness (deaths, stroke and systemic embolism) and the safety (major clinically significant and not significant bleeding) were investigated within 3 months.