Synthesis of Novel Hydrazide–Hydrazone Compounds and In Vitro and In Silico Investigation of Their Biological Activities against AChE, BChE, and hCA I and II

Abstract

The abnormal levels of the human carbonic anhydrase isoenzymes I and II (hCA I and II) and cholinesterase enzymes, namely, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are linked with various disorders including Alzheimer's disease. In this study, six new nicotinic hydrazide derivatives (7−12) were designed and synthesized for the first time, and their inhibitory profiles against hCA I, hCA II, AChE, and BChE were investigated by in vitro assays and in silico studies. The structures of novel molecules were elucidated by using spectroscopic techniques and elemental analysis. These molecules showed inhibitory activities against hCA I and II with IC 50 values ranging from 7.12 to 45.12 nM. Compared to reference drug acetazolamide (AZA), compound 8 was the most active inhibitor against hCA I and II. On the other hand, it was determined that IC 50 values of the tested molecules ranged between 21.45 and 61.37 nM for AChE and between 18.42 and 54.74 nM for BChE. Among them, compound 12 was the most potent inhibitor of AChE and BChE, with IC 50 values of 21.45 and 18.42 nM, respectively. In order to better understand the mode of action of these new compounds, state-of-the-art molecular modeling techniques were also conducted.

Investigation of Newly Synthesized Fluorinated Isatin-Hydrazones by In Vitro Antiproliferative Activity, Molecular Docking, ADME Analysis, and e-Pharmacophore Modeling

“…Hydrazones, which are employed in diverse domains of organic chemistry, are renowned for their versatility and are recognized as a significant category of compounds for new drug development . Hydrazones, which are regarded as a significant group of organic compounds, encompass CN bonds that are conjugated with the lone pair of electrons of a functional nitrogen atom, and possess the structure R 1 R 2 CNNH 2 , Nitrogen atoms exhibit nucleophilic properties, whereas carbon atoms possess both electrophilic and nucleophilic characteristics. , Hydrazone linkages in pharmaceutical materials have significant value in numerous transformations and have attracted great interest because of their many biological and clinical applications, such as anticancer, antimicrobial, antioxidant, antituberculosis, anti-inflammatory, antiviral, antiproliferative, and enzyme inhibitory activities. − …”