A novel acyl hydrazone schiff’s bases of benzimidazole-2-thiol

A series of novel acyl hydrazone derivatives of benzimidazole-2-thiol were synthesized. The acylhydrazide was condensed with a series of aromatic substituted aldehydes to yield the tetra decylhydrazone Schiff”s bases of benzimidazole-2-thiol. The acylhydrazide was taken in methanol in round bottom flask added 2-3 drops acetic acid and refluxed on hotplate the reaction mixture was monitored with TLC. After completion of reaction the product was precipitated in ice cool water, washed and dried. The synthesized compounds were screened for different biological activities such as antimicrobial, antihistamine, neutropic, analgesic, antiprotozoal, antimalarial, antiallergic, antioxidant, anticonvulsant, anti-tubercular and have shown a good results.

Efficient artificial light-harvesting systems based on aggregation-induced emission constructed in supramolecular gels

Based on a new designed acyl hydrazone gelator (G2), we developed an efficient energy transfer supramolecular organogel in glycol with two different hydrophobic fluorescent dyes rhodamine B (RhB) and acridine...

Reactivity of N-acyl hydrazone probes with the mammalian proteome

Small molecule probes with distinct reactivities are useful tools for the identification and characterization of protein modifications and function.

Synthesis of spiro(indoline-2,3′-hydropyridazine) via an “on-water” [4 + 2] annulation reaction

An on-water [4 + 2] annulation reaction between 2-methyl-3H-indolium salt and α-bromo N-acyl hydrazone has been developed. The environmentally friendly strategy provides the first facile access to spiro(indoline-2,3'-hydropyridazine) scaffolds.

In vitro selection implicates ROP1 as a resistance gene for an experimental therapeutic benzoquinone acyl hydrazone in Toxoplasma gondii

Toxoplasma gondii is a globally distributed apicomplexan parasite and the causative agent of toxoplasmosis in humans. While pharmaceuticals exist to combat acute infection, they can produce serious adverse reactions, demonstrating a need for enhanced therapies. KG8 is a benzoquinone acyl hydrazone chemotype identified from a previous chemical screen for which we previously showed in vitro and in vivo efficacy against T. gondii. However, the genetic target and mechanism of action of KG8 remain unknown. To investigate potential targets, we generated resistant T. gondii lines by chemical mutagenesis followed by in vitro selection. Whole genome sequencing of resistant clones revealed a P207S mutation in the gene encoding rhoptry organelle protein 1 (ROP1), in addition to two lesser resistance-conferring mutations in the genes for rhoptry organelle protein 8 (ROP8) and a putative ADP/ATP carrier protein (TGGT1_237700). Expressing ROP1P207S in parental parasites was sufficient to confer significant (10.3-fold increased EC50) KG8 resistance. After generating a library of mutants carrying hypermutated rop1 alleles followed by KG8 pressure, we sequenced the most resistant clonal isolate (>16.9-fold increased EC50) and found independent recapitulation of the P207S mutation, along with three additional mutations in the same region. We also demonstrate that a rop1 knockout strain is insensitive to KG8. These data implicate ROP1 as a putative resistance gene of KG8. This work further identifies a compound which can be used in future studies to better understand ROP1 function and highlights this novel chemotype as a potential scaffold for the development of improved T. gondii therapeutics.

Design, Synthesis and Biological Evaluation of Novel Triazole N-acylhydrazone Hybrids for Alzheimer’s Disease

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that involves different pathogenic mechanisms. In this regard, the goal of this study was the design and synthesis of new compounds with multifunctional pharmacological activity by molecular hybridization of structural fragments of curcumin and resveratrol connected by an N-acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative 3e showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aβ42 oligomers in neuronal SH-SY5Y cells. In parallel, compound 3e showed a good profile of safety and ADME parameters. Taken together, these results suggest that 3e could be considered a lead compound for the further development of AD therapeutics.