Recent applications of hydantoin and thiohydantoin in medicinal chemistry

Cho, SeoHyun; Kim, Seokho; Shin, Dongyun

doi:10.1016/j.ejmech.2018.12.066

Cited by 143 publications

(74 citation statements)

References 110 publications

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“…The multifactorial nature of AD and the absence of an effective and long-lasting therapy so far, have stimulated medicinal chemists to follow multitarget drug design strategies based even on repositioning of approved drugs [17]. A recent example is represented by the antidiabetic drugs rosiglitazone and pioglitazone, as seen in Figure 1, isosteric analogues of hydantoins [18] that competitively inhibit MAO B with a low- and submicromolar K i value, respectively, for the human enzyme. The high specificity shown by pioglitazone, and the crystallographic data in support of it [19], justify the possible repositioning of these molecules among promising neuroprotective agents.…”

Section: Introductionmentioning

confidence: 99%

A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer’s Disease

et al. 2019

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The orphan drug dantrolene (DAN) is the only therapeutic treatment for malignant hyperthermia (MH), a pharmacogenetic pathology affecting 0.2 over 10,000 people in the EU. It acts by inhibiting ryanodine receptors, which are responsible for calcium recruitment in striatal muscles and brain. Because of its involvement in calcium homeostasis, DAN has been successfully investigated for its potential as neuroprotecting small molecule in several animal models of Alzheimer’s disease (AD). Nevertheless, its effects at a molecular level, namely on putative targets involved in neurodegeneration, are still scarcely known. Herein, we present a prospective study on repurposing of DAN involving, besides the well-known calcium antagonism, inhibition of monoamine oxidase B and acetylcholinesterase, cytoprotection from oxidative insult, and activation of carnitine/acylcarnitine carrier, as concurring biological activities responsible for neuroprotection.

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Section: Introductionmentioning

confidence: 99%

A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer’s Disease

et al. 2019

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“…The object was to combine the 1,2,4-triazole nucleus to the cinnamaldehyde since it is known that more e cacious antimicrobial substances can be discovered by adding two biologically effective components together into a single molecular structure [41,42]. Thereafter product Oxadiazole compound (12) was obtained as a result of ring closure reaction of hydrazide compound (5) with CS 2 in basic media. The NH and NH 2 peaks resulting from the hydrazide compound disappeared in both the FT-IR and 1 H NMR data of the oxadiazol derivative compound.…”

Section: Discussionmentioning

confidence: 99%

“…Organic molecules bearing heterocyclic compounds have received a signi cant consideration in all elds of life comprising medicinal, pharmaceutical, combinatorial, natural resources, agriculture and dyes products [3,12]. Hybrid compounds are molecules with two or more structural elds, which have diverse dual activities and biological features.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antimicrobial, Antiproliferative Evaluation of Novel Quinolone and Conazole Analogues via Conventional and Microwave Techniques

Ceylan

Cebeci

Demirbaş

et al. 2021

Preprint

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1,2,4-Triazole-3-one (3), acquired from cinnemaldehyde was converted to the corresponding carbox(thio)amides via several steps (6a-c). Their reaction with sodium hydroxide gave the 1,2,4-triazole derivatives (7a-c). Compound 3 treatment with 2-bromo-1-(4-chlorophenyl) ethanone or 2-chloro-1-(2,4-dichlorophenyl)ethanone afforded the compounds 8a,b and by reducing these compounds reduction products were obtained (9a,b). The synthesis of (10a-e) was carried out by the reaction compounds 9a,b with different benzyl chlorides. Then oxadiazol derivative (12) was obtained by ring closure from hydrazide compound 5. Subsequently compounds 3, 7a-c and 12 were treated with various amines in the presence of formaldehyde to yield Mannich bases (11a-e, 14a-e, 13a,b). Microwave-assisted and conventional techniques were utilized for the syntheses. The structures of newly synthesized compounds were illuminated by spectroscopic methods. Their antimicrobial (MIC method), and anticancer activities (Abay’s method) were examined. Results showed that most of the compounds exhibited good antimicrobial activities. Especially compounds 14a-e which is a mannich base showed very good antitubercular activity against Mycobacterium smegmatis compared with Streptomycin standard drug. Also compounds 8a and 9b have been found to have strong antiproliferative effects on the HeLa cervical cancer cells and also these compounds did not have cytotoxic effect on normal cell.

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“…The biological activities of heterocyclic compounds are increased by a variety of functional groups alone or combined in different positions such as the para or ortho positions in a phenyl ring [15,16]. Among these bioactive compounds is thiohydantoin, which is an important class of biologically active compounds [17,18]. Thiohydantoins are sulfur analogs of hydantoins with one or two carbonyl groups that have been substituted by thiocarbonyl groups [19].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of novel 2-thioxo-4-imidazolidinone derivatives and evaluation of their antibacterial, and antifungal activities

2021

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The infectious diseases caused by antimicrobials pathogens are difficult, harmful, and sometimes impossible to treat. Therefore, design new drugs to treat antimicrobial infections is the biggest challenge for modern medicine. 2-Thioxo-4-imidazolidinone is used for the synthesis of a wide variety of new substituted imidazolidinone derivatives. In this study, we designing eight novel compounds derived for the 2-thioxo-4-imidazolidinones (5ah). The preparation was in two steps via Micheal addition of phenyl hydrazide (2a), 4-methyl phenyl hydrazide 2b on N-substituted maleimides 1a-d in ethanol, and the second step by reaction of maleimide derivatives with cyclohexyl isothiocyanate 4 in acetonitrile. The chemical structures of the compounds were identified using FT-IR, 1 H-NMR, 13 C-NMR, and mass spectra, as well as the melting point. The antibacterial and antifungal evaluation was carried out to target their activities. Compound N-(5-(2-((4-chlorophenyl)amino)-2-oxoethyl)-3cyclohexyl-4-oxo-2-thioxoimidazolidin-1-yl) benzamide (5b) exhibited antibacterial activity toward Staphylococcus aureus and Pseudomonas aeruginosa with equal minimum inhibitory concentration (MIC) values of 25 mg/mL. Compounds N-(3-cyclohexyl-4-oxo-5-(2-oxo-2-(phenylamino)ethyl)-2-thioxoimidazolidin-1-yl) benzamide (5a), N-(5-(2-((4-chlorophenyl)amino)-2-oxoethyl)-3-cyclohexyl-4-oxo-2-thioxoimidazolidin-1-yl) benzamide (5b), N-(5-(2-((4-bromophenyl)amino)-2-oxoethyl)-3-cyclohexyl-4-oxo-2-thioxo imidazolidin-1-yl) benzamide (5c), and N-(3-cyclohexyl-4-oxo-5-(2-oxo-2-(phenylamino)ethyl)-2-thioxoimidazolidin-1-yl)-4methyl benzamide (5e) exhibited antifungal activity toward Candida albicans, while all compounds exhibited antifungal activity toward Aspergillus niger except for compound 5h, with various MIC values. In conclusion, the results demonstrate that the new compounds have to promise as antifungal agents. Moreover, compound 5b could develop as an antibacterial agent.

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Recent applications of hydantoin and thiohydantoin in medicinal chemistry

Cited by 143 publications

References 110 publications

A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer’s Disease

A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer’s Disease

Synthesis and Antimicrobial, Antiproliferative Evaluation of Novel Quinolone and Conazole Analogues via Conventional and Microwave Techniques

Synthesis of novel 2-thioxo-4-imidazolidinone derivatives and evaluation of their antibacterial, and antifungal activities

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