Introducing Casbah, Kronus, and MmasiCarm, Members of the Mycobacteriophage Subcluster B3.

Background: As part of a large science education effort, bacteriophages that lyse mc155 continue to be discovered.

Materials And Methods: Phages were isolated from soil samples from urban sites in the Northeastern United States. Their genomes were sequenced, assembled, and bioinformatically compared.

,2,6-Trisubstituted 1-benzimidazole derivatives as a new scaffold of antimicrobial and anticancer agents: design, synthesis, evaluation, and studies.

Compounds containing benzimidazole moiety occupy privileged chemical space for discovering new bioactive substances. In continuation of our recent work, 69 benzimidazole derivatives were designed and synthesized with good to excellent yields of 46-99% using efficient synthesis protocol sodium metabisulfite catalyzed condensation of aromatic aldehydes with -phenylenediamines to form 2-arylbenzimidazole derivatives followed by -alkylation by conventional heating or microwave irradiation for diversification. Potent antibacterial compounds against MSSA and MRSA were discovered such as benzimidazole compounds 3k (2-(4-nitrophenyl), -benzyl), 3l (2-(4-chlorophenyl), -(4-chlorobenzyl)), 4c (2-(4-chlorophenyl), 6-methyl, -benzyl), 4g (2-(4-nitrophenyl), 6-methyl, -benzyl), and 4j (2-(4-nitrophenyl), 6-methyl, -(4-chlorobenzyl)) with MIC of 4-16 μg mL.

Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress.

The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells.

Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses.

Drugs targeting SARS-CoV-2 could have saved millions of lives during the COVID-19 pandemic, and it is now crucial to develop inhibitors of coronavirus replication in preparation for future outbreaks. We explored two virtual screening strategies to find inhibitors of the SARS-CoV-2 main protease in ultralarge chemical libraries. First, structure-based docking was used to screen a diverse library of 235 million virtual compounds against the active site.

Synthesis of a Series of Novel 2-Amino-5-substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole Derivatives as Potential Anticancer, Antifungal and Antibacterial Agents.

Background: Many compounds containing a five-membered heterocyclic ring display exceptional chemical properties and versatile biological activities.

Objective: The objective of the present study was to prepare the 5-substituted 2-amino-1,3,4- oxadiazole and 2-amino-1,3,4-thiadiazole derivatives and evaluate their potential anticancer, antibacterial and antifungal activities.

Methods: Twenty-seven derivatives were synthesized by iodine-mediated cyclization of semicarbazones or thiosemicarbazones obtained from condensation of semicarbazide or thiosemicarbazide and aldehydes.

Docking Finds GPCR Ligands in Dark Chemical Matter.

High-throughput screening has revealed dark chemical matter, a set of drug-like compounds that has never shown bioactivity despite being extensively assayed. If dark molecules are found active at a therapeutic target, their extraordinary selectivity profiles make excellent starting points for drug development. We explored if ligands of therapeutically relevant G-protein-coupled receptors could be discovered by structure-based virtual screening of the dark chemical matter.