New 2-alkylthio-1-benzylimidazole-5-carboxylic acid derivatives targeting gp41: design, synthesis and in vitro anti-HIV activity evaluation.

Background Although current available medications have increased the quality of life in HIV-infected patients, there are still some shortcomings in HIV treatment arising from viral resistance, drug side effects and high cost of medication. Therefore, there is an urgent need for some suitable HIV inhibitors with different mechanisms of action. Gp41, located on the HIV cell surface, plays an important role in the fusion of viral and host cell membranes.

Design, synthesis, in silico studies, and antiproliferative evaluations of novel indolin-2-one derivatives containing 3-hydroxy-4-pyridinone fragment.

Keeping in view the pharmacological properties of indolinones as promising scaffold as kinase inhibitors, herein, a novel series of 3-hydrazonoindolin-2-one derivatives bearing 3-hydroxy-4-pyridinone moiety were synthesized, studied by molecular docking, and fully characterized by spectroscopic techniques. All the prepared compounds were evaluated for their cytotoxicity attributes against a panel of tumor cell lines, including non-small cell lung cancer (A549), breast carcinoma (MCF-7), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). They displayed moderate to promising antiproliferative effects toward A549 and MCF-7 cells but remarkable results against AML and CML.

design of novel FAK inhibitors using integrated molecular docking, 3D-QSAR and molecular dynamics simulation studies.

Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays a crucial role in integrin signaling that regulates essential cellular functions including growth, motility, proliferation and survival in different types of cells. Interestingly, it has also shown to be up-regulated in various types of tumors, hence it has emerged as a significant therapeutic target for the development of selective inhibitors. In present work, with the aim of achieving further insight into the structural characteristics required for the FAK inhibitory activity, a combined approach of molecular modeling studies including molecular docking, three-dimensional quantitative structure activity relationship (3D-QSAR) and molecular dynamics (MD) simulation were carried out on a series of 7-pyrrolo[2,3-]pyrimidine and thieno[3,2-]pyrimidine FAK inhibitors.

Recent Advances in the Design and Development of Non-nucleoside Reverse Transcriptase Inhibitor Scaffolds.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have always been an important part of the anti-HIV-1 combination therapy known as combination antiretroviral therapy (cART) since 1996. The use of NNRTIs for about 22 years has led to some mutations in the residues that compose the reverse transcriptase active site, resulting in the emergence of drug-resistant viruses. Thus, the search for new potent NNRTIs with an improved safety profile and activity against drug-resistant HIV strains is indispensable, and many hit and lead NNRTIs have been discovered in the last decade.

2-(3,5-Dioxo-4-aza-tri-cyclo-[5.2.1.0(2,6)]dec-8-en-4-yl)acetic acid.

The asymmetric unit of the title compound, C11H11NO4, contains two mol-ecules, A and B, with different conformations: in mol-ecule A, the norborne and carb-oxy-lic acid groups lie to the same side of the heterocycle, whereas in a mol-ecule B, they lie on opposite sides. In the crystal, the A mol-ecules form R 2 (2)(8) carb-oxy-lic acid inversion dimers, linked by pairs of O-H⋯O hydrogen bonds. The B mol-ecules link to one of the ketone O atoms of the A mol-ecule by an O-H⋯O inter-action, resulting in tetra-mers (two A and two B mol-ecules).