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The regio- and stereospecific synthesis ofO-methyl-chiro-inositols andO-methyl-scyllo-inositol was achieved, starting fromp-benzoquinone. After preparing dimethoxy conduritol-B as a key compound, regiospecific bromination of the alkene moiety of dimethoxy conduritol-B and acid-catalyzed ring opening of dimethoxydiacetate conduritol-B epoxide with Ac2O afforded the desired newchiro-inositol derivatives andscyllo-inositol derivative, respectively. Spectroscopic methods were employed for the characterization of all synthesized compounds. The novel inositols (11-17) had effective inhibition profiles against human carbonic anhydrase isoenzymes I and II (hCA I and II) and acetylcholinesterase (AChE). The novel inositols11-17were found to be effective inhibitors against AChE, hCA I, and hCA II enzymes.K(i)values were calculated in the range of 87.59 +/- 7.011 to 237.95 +/- 17.75 mu M for hCA I, 65.08 +/- 12.39 to 538.98 +/- 61.26 mu M for hCA II, and 193.28 +/- 43.13 to 765.08 +/- 209.77 mu M for AChE, respectively. Also, due to the inhibitory effects of the novel inositols11-17against the tested enzymes, these novel inositols are potential drug candidates to treat some diseases such as glaucoma, epilepsy, leukemia, and Alzheimer's disease., Ordu University Scientific Research Projects Coordination Unit (ODU/BAP) [AR-1324], The authors are indebted to Ordu University Scientific Research Projects Coordination Unit (ODU/BAP, Grant No: AR-1324) for financial support of this study.

Alzheimer's disease (AD) is one of the cognitive or memory-related impairments occurring with advancing age. Since its exact mechanism is not known, the full therapy has still not been found. Acetylcholinesterase (AChE) has been reported to be a viable therapeutic target for the treatment of AD and other dementias. To this end, acetylcholinesterase inhibitors (AChEIs) are commonly used. AChE is a member of the hydrolase enzyme family. A hydrolase is an enzyme that catalyzes the hydrolysis of a chemical bond. AChE is useful for the development of novel and mechanism-based inhibitors. It has a role in the breakdown of acetylcholine (ACh) neurotransmitters, such as acetylcholine-mediated neurotransmission. AChEIs are the most effective approaches to treat AD. AChE hydrolyzes ACh to acetate and choline, as an important neurotransmitter substance. Recently, Gulcin and his group explored new AChEIs. The most suggested mechanism for AD is the deficiency of ACh, which is an important neurotransmitter. In this regard, AChEIs are commonly used for the symptomatic treatment of AD. They act in different ways, such as by inhibiting AChE, protecting cells from free radical toxicity and beta-amyloid-induced injury or inhibiting the release of cytokines from microglia and monocytes. This review focuses on the role of AChEIs in AD using commonly available drugs. Also, the aim of this review is to research and discuss the role of AChEIs in AD using commonly available drugs. Therefore, in our review, related topics like AD and AChEIs are highlighted. Also, the latest work related to AChEIs is compiled. In recent research studies, novel natural and synthetic AChEIs, used for AD, are quite noteworthy. These studies can be very promising in detecting potent drugs against AD.

Humic acid is a principal component of humic substances, which is the major organic constituents of soil, coal, peat, many upland streams, dystrophic lakes, and ocean water. It is produced by the biodegradation of dead organic matters. Humic substances contain major groups for chemistry, such as polyphenols, polycarboxylic acids, carbonyl groups, and peroxides. The presence of carboxylate and phenolate groups gives the humic acids the ability to form complexes with ions such as, Fe2+, Fe3+, Mg2+, and Ca2+. Acetylcholinesterase (AChE, E.C.3.1.1.7), also known as AChE, is a hydrolase that hydrolyses the neurotransmitter acetylcholine. AChE is found at mainly neuromuscular junctions and cholinergic brain synapses, where its activity serves to terminate synaptic transmission. Reduction in the activity of the cholinergic neurons is a well-known property of Alzheimer's disease. Acetylcholinesterase inhibitors are employed to reduce the rate at which acetylcholine (ACh) is broken down, so that increasing the concentration of ACh in the brain and fighting the loss of ACh caused by the death of cholinergic neurons. Natural compounds are very important for Alzheimer's disease. Humic substances are the major natural bio-polyelectrolyte and contain major groups for chemistry. In this study, the effect of humic acid was investigated on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE, E.C.3.1.1.8) enzymes. AChE and BChE inhibition studies were performed according to Ellman method. IC50 and K-i values were calculated for humic acid. These values were found 0.474 and 0.181 nM for AChE and 20.83 and 0.208 nM for BChE, respectively. The inhibition type was determined as competitive., Distinguished Scientist Fellowship Program, King Saud University, S.H. Alwasel would like to thank the Distinguished Scientist Fellowship Program, King Saud University for their support.