Synthesis, biochemical and computational evaluations of novel bis-acylhydrazones of 2,2'-(1,1'-biphenyl)-4,4'-diylbis(oxy))di(acetohydrazide) as dual cholinesterase inhibitors.

A series of twenty-seven bis(acylhydrazones) were successfully synthesized with high yields through a multistep process, which entailed the esterification of hydroxyl groups, hydrazination with an excess of hydrazine hydrate, and subsequent reactions with various carbonyl moieties (aldehydes). In the final stage of synthesis, different chemical species including aromatic, heterocyclic, and aliphatic compounds were integrated into the framework. The resulting compounds were characterized using several spectroscopic techniques (1H NMR, 13C NMR, and mass spectrometry). Their anticholinesterase activities were assessed in vitro by examining their interactions with two cholinesterase enzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the synthesized hits, compounds 3, 5, 6, 9-12, and 14 exhibited good to moderate inhibition of AChE. Specifically, 10 (IC50 = 26.3 ± 0.4 µM) and 11 (IC50 = 28.4 ± 0.5 µM) showed good inhibitory activity against AChE, while 9, 12, 3, and 6 exhibited significant inhibition potential against AChE with IC50 values ranging from 35.2 ± 1.1 µM to 64.4 ± 0.3 µM. On the other hand, 5 (IC50 = 22.0 ± 1.1 µM) and 27 (IC50 = 31.3 ± 1.3 µM) displayed significant, and 19 (IC50 = 92.6 ± 0.4 µM) showed moderate inhibitory potential for BChE. Notably, 5 and 27 exhibited dual inhibition of AChE and BChE, with greater potency than the standard drug galantamine. The binding patterns of these molecules within the binding cavities of AChE and BChE were anticipated by molecular docking which showed good correlation with our in vitro findings. Further structural optimization of these molecules may yield more potent AChE and BChE inhibitors.

Application of connectivity index of cubic fuzzy graphs for identification of danger zones of tsunami threat.

Fuzzy graphs are very important when we are trying to understand and study complex systems with uncertain and not exact information. Among different types of fuzzy graphs, cubic fuzzy graphs are special due to their ability to represent the membership degree of both vertices and edges using intervals and fuzzy numbers, respectively. To figure out how things are connected in cubic fuzzy graphs, we need to know about cubic α-strong, cubic ß-strong and cubic δ-weak edges. These concepts better help in making decisions, solving problems and analyzing things like transportation, social networks and communication systems. The applicability of connectivity and comprehension of cubic fuzzy graphs have urged us to discuss connectivity in the domain of cubic fuzzy graphs. In this paper, the terms partial cubic α-strong and partial cubic δ-weak edges are introduced for cubic fuzzy graphs. The bounds and exact expression of connectivity index for several cubic fuzzy graphs are estimated. The average connectivity index for cubic fuzzy graphs is also defined and some results pertaining to these concepts are proved in this paper. The results demonstrate that removing some vertices or edges may cause a change in the value of connectivity index or average connectivity index, but the change will not necessarily be related to both values. This paper also defines the concepts of partial cubic connectivity enhancing node and partial cubic connectivity reducing node and some related results are proved. Furthermore, the concepts of cubic α-strong, cubic ß- strong, cubic δ-weak edge, partial cubic α-strong and partial cubic δ-weak edges are utilized to identify areas most affected by a tsunami resulting from an earthquake. Finally, the research findings are compared with the existing methods to demonstrate their suitability and creativity.