Nitrogen-bridgehead compounds: overview, synthesis, and outlook on applications.

The nitrogen-bridgehead is a common structural motif present in a multitude of natural products. As many of these abundant compounds exhibit biological activities, against cancer or bacteria, these derivatives are of high interest. While natural products are often associated with problematic characteristics, such as elaborate separation processes, high molecular complexity and limited room for derivatization, purely synthetic approaches can overcome these challenges.

Inhibition of protein translational machinery in triple-negative breast cancer as a promising therapeutic strategy.

Y-box binding protein-1 (YB-1) is a proto-oncogenic protein associated with protein translation regulation. It plays a crucial role in the development and progression of triple-negative breast cancer (TNBC). In this study, we describe a promising approach to inhibit YB-1 using SU056, a small-molecule inhibitor.

Access to Artemisinin-Triazole Antimalarials Organo-Click Reaction: High / Activity against Multi-Drug-Resistant Malaria Parasites.

Malaria is one of the most widespread diseases worldwide. Besides a growing number of people potentially threatened by malaria, the consistent emergence of resistance against established antimalarial pharmaceuticals leads to an urge toward new antimalarial drugs. Hybridization of two chemically diverse compounds into a new bioactive product is a successful concept to improve the properties of a hybrid drug relative to the parent compounds and also to overcome multidrug resistance.

Dipeptide-catalysed Michael reaction under physiological conditions: Examination of potential bioorthogonality.

Reactions for drug synthesis under cell-like conditions or even inside living cells can potentially be used e.g., to minimize toxic side effects, to maximize bioactive compound efficacy and/or to address drug delivery problems.

Autofluorescent Artemisinin-Benzimidazole Hybrids via Organo-Click Reaction: Study of Antiviral Properties and Mode of Action in Living Cells.

Drug modification by a fluorescent label is a common tool for studying its mechanism of action with fluorescence microscopy techniques. However, the attachment of a fluorescent label can significantly alter the polarity, solubility, and biological activity of the investigated drug, and, as a result, the studied mechanism of action can be misrepresented. Therefore, developing efficient drugs, which are inherently fluorescent and can be tracked directly in the cell is highly favorable.

Iron-Catalyzed Olefin Metathesis: Recent Theoretical and Experimental Advances.

The "metathesis reaction" is a straightforward and often metal-catalyzed chemical reaction that transforms two hydrocarbon molecules to two new hydrocarbons by exchange of molecular fragments. Alkane, alkene and alkyne metathesis have become an important tool in synthetic chemistry and have provided access to complex organic structures. Since the discovery of industrial olefin metathesis in the 1960s, many modifications have been reported; thus, increasing scope and improving reaction selectivity.

Four-Step Domino Reaction Enables Fully Controlled Non-Statistical Synthesis of Hexaarylbenzene with Six Different Aryl Groups*.

Hexaarylbenzene (HAB) derivatives are versatile aromatic systems playing a significant role as chromophores, liquid crystalline materials, molecular receptors, molecular-scale devices, organic light-emitting diodes and candidates for organic electronics. Statistical synthesis of simple symmetrical HABs is known via cyclotrimerization or Diels-Alder reactions. By contrast, the synthesis of more complex, asymmetrical systems, and without involvement of statistical steps, remains an unsolved problem.

The Artemisinin-Derived Autofluorescent Compound BG95 Exerts Strong Anticytomegaloviral Activity Based on a Mitochondrial Targeting Mechanism.

Human cytomegalovirus (HCMV) is a major human pathogen associated with severe pathology. Current options of antiviral therapy only partly satisfy the needs of a well-tolerated long-term treatment/prophylaxis free from drug-induced viral resistance. Recently, we reported the strong antiviral properties in vitro and in vivo of the broad-spectrum anti-infective drug artesunate and its optimized derivatives.

Target verification of artesunate-related antiviral drugs: Assessing the role of mitochondrial and regulatory proteins by click chemistry and fluorescence labeling.

Human cytomegalovirus (HCMV) infection is associated with serious pathology such as transplant rejection or embryonic developmental defects. Antiviral treatment with currently available drugs targeting viral enzymes is often accompanied with severe side effects and the occurrence of drug-resistant viruses. For this reason, novel ways of anti-HCMV therapy focusing on so far unexploited small molecules, targets and mechanisms are intensively studied.

In vivo proof-of-concept for two experimental antiviral drugs, both directed to cellular targets, using a murine cytomegalovirus model.

Infections with the human cytomegalovirus (HCMV) cause serious medical problems including organ rejection and congenital infection. Treatment of HCMV infections with currently available medication targeting viral enzymes is often accompanied with severe side effects and the occurrence of drug-resistant viruses. This demands novel therapeutical approaches like targeting genetically stable host cell proteins that are crucial for virus replication.

Three-Component Domino Knoevenagel/Vinylogous Michael Reaction: Entry to Challenging o-Terphenyls.

An unprecedented organocatalytic three-component domino Knoevenagel/vinylogous Michael reaction starting from simple enolizable aldehydes, malononitrile, and nitroolefins is reported. This facile two-step domino process provides a straightforward stereoselective route to multifunctional vinyl malononitrile products (up to 82 % yield, 85:15 d.r.