Synthesis and some enzyme inhibition effects of isoxazoline and pyrazoline derivatives including benzonorbornene unit

Abstract

Four new and four known isoxazoline derivatives were synthesized from the reactions of benzonorbornadiene with nitrile oxides formed from the corresponding benzaldehydes. Three new and one known pyrazoline derivatives were also synthesized from the reactions of the benzonorbornadiene with nitrile imines formed from the corresponding compounds. The synthesized nitrogenbased novel heterocyclic compounds were evaluated against the human carbonic anhydrase isoenzymes I and II (hCA I and hCA II), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes. The synthesized nitrogenbased novel heterocyclic compounds showed IC 50 values in the range of 2.69-7.01 against hCA I, 2.40-4.59 against hCA II, 0.81-1.32 µM against AChE, and 20.83-1.70 µM against BChE enzymes. On the contrary, nitrogen-based novel heterocyclic compounds demonstrated K i values between2.93 ± 0.59-8.61 ± 1.39 against hCA I, 2.05 ± 0.62-4.97 ± 0.95 against hCA II, 0.34 ± 0.02-0.92 ± 0.17 nM against AChE, and 0.50 ± 0.04-1.20 ± 0.16 µM against BChE enzymes. The synthesized nitrogen-based novel heterocyclic compounds exhibited effective inhibition profiles against both indicated metabolic enzymes. These results may contribute to the development of new drugs particularly to treat some disorders, which are widespread in the world including glaucoma and Alzheimer's diseases.

Vinyl functionalized 5,6‐dimethylbenzimidazolium salts: Synthesis and biological activities

“…[ 75 ] It is known that hydroxyl, carboxyl, phenyl, acyl, benzyl, cyanate, thiocyanate, aldehyde, methoxy, halogen, alcohol, and amine groups promote markedly significant inhibitory ability against enzymes. [ 71 ] However, the inhibitory effects of the compounds were observed to be lower than that of the standard inhibitor, AZA. The K i values of studied vinyl functionalized 5,6‐dimethylbenzimidazolium salts ( 1a–g ) against hCA I were decreased in the following order: AZA (K i : 81.2 ± 16.9 nM) < 1e (K i : 484.8 ± 62.6 nM) < 1d (K i : 545.0 ± 110.1 nM) < 1f (K i : 639.9 ± 59.8 nM) < 1g (K i : 803.6 ± 398.4 nM) < 1a (K i : 997.5 ± 176.2 nM) < 1b (K i : 1339.9 ± 169.4 nM) < 1c (K i : 1389.7 ± 243.2 nM) (Table 1).…”

“…CAIs show numerous bioactivities linked to many global diseases such as glaucoma, obesity, cancer, epilepsy, and osteoporosis. [70,71] Both CA I and CA II are the most studied isoenzymes. [72] While CA I is expressed in erythrocytes and the gastrointestinal tract, CA II is expressed in almost all tissues, especially in the eye, gastrointestinal tract, erythrocytes, bone osteoclasts, kidney, testis brain, and lung.…”

Design and Synthesis of Carbothioamide/Carboxamide-Based Pyrazoline Analogs as Potential Anticancer Agents: Apoptosis, Molecular Docking, ADME Assay, and DNA Binding Studies

“…Natural compounds have fewer N–N bonds than living creatures because they are more difficult to form. Heterocyclic analogs such as 1 H -pyrazole-1-carbothioamide/carboxamide are often used to design and develop physiologically active novel medications. − The pyrazoline core showed the potential anticancer activity − , and 1 H -pyrazole-1-carbothioamide types also exhibited biological activities such as antibacterial, antifungal, antiviral, antimalarial, antioxidant, anti-inflammatory, , , and analgesic effects. − Anticancer drugs have DNA as their primary intracellular target. In the present era, researchers are learning about the interaction of medications with DNA, and they believe that this interaction is responsible for DNA damage produced by malignant tumor cells’ inability to proliferate quickly. , Medication and micro-molecules commonly employ noncovalent, intercalation, groove binding, and electrostatic binding to interact with DNA.…”

Synthesis and Biological Activity of Some Bromophenols and Their Derivatives Including Natural Products

“…Increased AChE activity is closely linked to the pathology of some diseases including Lewy bodies dementia, Alzheimer's disease, with Lewy bodies, Myasthenia gravis, and glaucoma. It is known that abnormal BChE activity is associated with many diseases, including cardiovascular diseases, diabetes, hepatocellular carcinoma, chronic liver disease, metabolic syndrome, postoperative delirium as well as organophosphate and metal poisoning [37,51] . In compounds 5 and 27 , respectively, a considerable increase in anti‐BChE activity was observed after swapping from a 3‐methylbenzyl group to a benzyl group.…”

“…It is known that abnormal BChE activity is associated with many diseases, including cardiovascular dis- eases, diabetes, hepatocellular carcinoma, chronic liver disease, metabolic syndrome, postoperative delirium as well as organophosphate and metal poisoning. [37,51] In compounds 5 and 27, respectively, a considerable increase in anti-BChE activity was observed after swapping from a 3-methylbenzyl group to a benzyl group. Derivative 28 has a K i of 6.67 nM, making it the third most effective molecule against BChE among the synthesized compounds.…”