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 IC₅₀ 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 IC₅₀ 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 IC₅₀ 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.

In this study, some Schiff bases derived from 4-aminoantipyrine (4-AAP) (VI–X) were synthesized, characterized by elemental analysis (C, H, N) and three spectral techniques (FT-IR, ¹H, and ¹³C NMR), and then their antioxidant activity was investigated by employing four different methods. Subsequently, the inhibitory influences of the synthesized molecules against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase enzymes were tested. More importantly, the cytotoxic effects of all title molecules were also evaluated on HeLa human cervical cancer and L929 mouse fibroblast cell lines. According to the results obtained, compound (VI) (IC₅₀: 16.82 ± 0.17 μM) showed higher ABTS cation radical scavenging activity than BHA (IC₅₀: 17.59 ± 0.10 μM). In CUPRAC assay, it was determined that the activity ordering of the bioactive molecules has been determined as VII > X > VII > α-TOC > IX > I > II > V > VI. In AChE assay, compound (I) indicated a high potent inhibition activity with 91.75 ± 1.15% better than galanthamine. In BChE assay, compound (VII) had good BChE inhibition activity (78.76 ± 1.47%) better than galanthamine. Compound (V) showed strong tyrosinase inhibition activity with 52.85 ± 0.23% value at 200 μM concentration. Compound (III) showed the best cytotoxic effect on HeLa cells with an IC₅₀ dose of 21.47 µM. Consequently, it can be said that some of these synthesized molecules were potentially new anti-Alzheimer drug candidate molecules.