22906-89-4Relevant articles and documents
Synthesis and Biological Evaluation of Dantrolene-Like Hydrazide and Hydrazone Analogues as Multitarget Agents for Neurodegenerative Diseases
Bolognino, Isabella,Giangregorio, Nicola,Tonazzi, Annamaria,Martínez, Antón L.,Altomare, Cosimo D.,Loza, María I.,Sablone, Sara,Cellamare, Saverio,Catto, Marco
, p. 2807 - 2816 (2021)
Dantrolene, a drug used for the management of malignant hyperthermia, had been recently evaluated for prospective repurposing as multitarget agent for neurodegenerative syndromes, including Alzheimer's disease (AD). Herein, twenty-one dantrolene-like hydrazide and hydrazone analogues were synthesized with the aim of exploring structure-activity relationships (SARs) for the inhibition of human monoamine oxidases (MAOs) and acetylcholinesterase (AChE), two well-established target enzymes for anti-AD drugs. With few exceptions, the newly synthesized compounds exhibited selectivity toward MAO B over either MAO A or AChE, with the secondary aldimine 9 and phenylhydrazone 20 attaining IC50 values of 0.68 and 0.81 μM, respectively. While no general SAR trend was observed with lipophilicity descriptors, a molecular simplification strategy allowed the main pharmacophore features to be identified, which are responsible for the inhibitory activity toward MAO B. Finally, further in vitro investigations revealed cell protection from oxidative insult and activation of carnitine/acylcarnitine carrier as concomitant biological activities responsible for neuroprotection by hits 9 and 20 and other promising compounds in the examined series.
Comparative study of microwave assisted and conventional synthesis of furfuraldehyde based hydrazone derivatives and their metal complexes with biological evaluation
Jabeen, Mussarat,Mehmood, Karamat,Khan, Misbahul Ain,Nasrullah, Muhammad,Maqbool, Tahir,Jabeen, Farhat,Afzal, Misbah
, p. 431 - 436 (2017/01/24)
A series of acyl hydrazone derivatives were synthesized by the condensation of different hydrazides (benzohydrazide, isoniazid, nicotinic acid hydrazide and salicylhydrazide) and 5-(4′-nitrophenyl) furan-2-carbaldehyde. These hydrazones were subjected for metal complexation to yield copper(II) and nickel(II) complexes using conventional and microwave irradiation method. The microwave method was found to be successful with nearly the same or higher yields and shorter reaction time. The synthesized compounds were characterized by EIMS, CHN analysis, FTIR and NMR spectroscopy. All the synthesized compounds were screened for their antibacterial and antioxidant activities.
Phenylhydrazones as Correctors of a Mutant Cystic Fibrosis Transmembrane Conductance Regulator
Nieddu, Erika,Pollarolo, Benedetta,Mazzei, Marco T.,Anzaldi, Maria,Schenone, Silvia,Pedemonte, Nicoletta,Galietta, Luis J. V.,Mazzei, Mauro
, p. 112 - 123 (2016/02/09)
The phenylhydrazone RDR-1 is endowed with moderate activity as F508del-CFTR corrector; nevertheless, its simple structure enables stimulating developments in this class of correctors. Therefore, we synthesized a number of phenylhydrazones 3 by reacting phenylhydrazine derivatives 1 with furfural derivatives 2. By the same reaction, also the pyridine derivatives 4, the thiophene derivatives 5, and the hydrazides 6 and 7 were prepared. All compounds were tested as F508del-CFTR correctors in the cystic fibrosis (CF) bronchial epithelial cell line CFBE41o-, using corr-4a and VX-809 as controls. Some of the tested compounds emerged as interesting F508del-CFTR correctors at 20 μM (3c) and 2 μM (5d). 3c and 5d administered together with VX-809 produced a satisfactory additivity of action. When the structure of 5d was overlapped with RDR-1 and five other established correctors, a shared central design was clearly visible. This fact may be of interest in the search for new F508del-CFTR correctors. Starting from RDR-1, a known F508del-CFTR corrector, some phenylhydrazones were synthesized. Two new compounds (3c and 5d) showed encouraging activity and, when administered together with the corrector VX-809, gave an additivity of action. Overlapping the molecular design of 5d with RDR-1 and other known correctors revealed a common structural moiety, which may help in the search for new drugs against cystic fibrosis.
