A new synthetic route towards multifunctionalized cyclic amidrazones for feeding chemical space.

In the context of growing impetus to develop new molecular scaffolds as well as a variety of 3D fragments to escape from flatland, we have reintroduced the accessibility of the underexplored azaheterocyclic amidrazones as promising bioisosteres. Herein, we present an original and versatile approach to synthesize cyclic amidrazones functionalized at different positions of the scaffold in view of diversifying the substitution pattern towards multifunctionalization, extension or fusion of the ring system and 3D-shaping of fragments. This unprecedented synthetic route represents a sweet achievement to cover further lead-like chemical space.

An attempt to prepare sulfonyl analogues of fotemustine: unexpected rearrangement to sulfamate during nitrosation step.

This paper describes a flexible strategy to access diethyl ((((-(2-chloroethyl)--nitrososulfamoyl)amino)arylmethyl) phosphonates, as aryl analogues of fotemustine. The new aryl sulfamidophosphonates prepared from 2-chloroethylamine were successfully obtained under eco-environmental conditions using ultrasound irradiation. These compounds did not produce the expected nitroso analogues of fotemustine after the nitrosation reaction but the corresponding sulfamates which were fully characterized.

Synthesis and biological evaluation of DIDS analogues as efficient inhibitors of RAD51 involved in homologous recombination.

RAD51 is a pivotal protein of the homologous recombination DNA repair pathway, and is overexpressed in some cancer cells, disrupting then the efficiency of cancer-treatments. The development of RAD51 inhibitors appears as a promising solution to restore these cancer cells sensitization to radio- or chemotherapy. From a small molecule identified as a modulator of RAD51, the 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), two series of analogues with small or bulky substituents on the aromatic parts of the stilbene moiety were prepared for a structure-activity relationship study.

Identification of sulfonamide compounds active on the insect nervous system: Molecular modeling, synthesis and biological evaluation.

Insect nicotinic acetylcholine receptors (nAChRs) are a recognized target for insecticide design. In this work, we have identified, from a structure-based approach using molecular modeling tools, ligands with potential selective activity for pests versus pollinators. A high-throughput virtual screening with the Openeye software was performed using a library from the ZINC database, thiacloprid being used as the target structure.

Impairments in learning and memory performances associated with nicotinic receptor expression in the honeybee Apis mellifera after exposure to a sublethal dose of sulfoxaflor.

Sulfoxaflor is a new insecticide which acts on the nicotinic acetylcholine receptor (nAChRs) in a similar way to neonicotinoids. However, sufloxaflor (SFX) is thought to act in a different manner and is thus proposed as an alternative in crop protection. The goal of this study is to evaluate the toxicity of SFX and its sublethal effect on the honeybee Apis mellifera after acute exposure.