Design, synthesis, and biological evaluation studies of novel quinazolinone derivatives as anticonvulsant agents

Zayed, Mohamed F.; Ahmed, Hany E. A.; Omar, Abdelsattar M.; Abdelrahim, Adel S.; El‐Adl, Khaled

doi:10.1007/s00044-013-0569-5

Cited by 32 publications

(33 citation statements)

References 18 publications

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“…4 Third fact explained that: substitution of the quinazolinone ring with halogens or an electron rich group at sixth or eighth positions greatly enhanced the anticonvulsant activity as in compounds (B) and (C) which have been reported to possess better activity, longer duration and lower toxicity than phenytoin. 1,21 Fig. 1 represents the structural similarities and pharmacophoric features of some reported anticonvulsants quinazolinones and our designed compounds.…”

Section: Rationale and Structure-based Designmentioning

confidence: 98%

“…Iodine was selected because it has received considerable attention in organic synthesis due to its high tolerance to air and moisture, low-cost, nontoxic nature, and ready availability. 1,22 The presence of iodine at sixth position increases the lipophilicity of the molecules, the hydrophobic surface of contact, the absorption and the distribution. 23 This study was carried out in hope of developing potent, safe, new and effective anticonvulsant agents with low doserelated toxicity and without idiosyncratic side effects.…”

Section: Rationale and Structure-based Designmentioning

confidence: 99%

“…Lipophilic substances are able to permeate into the brain interstitium in a relatively easy way. 1 Determination of brain-blood partitioning in vitro is difficult, timeconsuming, expensive, not always available and not suitable to screen a large collection of new chemicals. Therefore, an alternative method was used based on computerized models.…”

Section: Log P Correlationmentioning

confidence: 99%

“…Quinazolin-4(3H)-ones and their derivatives constitute an important class of heterocyclic compounds and are shown to have potent CNS activities such as anticonvulsant [1][2][3][4][5][6] and CNS depressant. 7 A literature survey revealed that the presence of an aromatic or aliphatic group at position 2 and a substituted aromatic ring at position 3 are necessary requirements for the CNS depression and anticonvulsant activities.…”

Section: Introductionmentioning

confidence: 99%

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Design, synthesis, molecular docking and anticonvulsant evaluation of novel 6-iodo-2-phenyl-3-substituted-quinazolin-4(3H)-ones

Ibrahim

El‐Adl

Al‐Karmalawy

2015

Bulletin of Faculty of Pharmacy, Cairo University

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A new series of 6-iodo-2-phenyl-3-substituted-quinazolin-4(3H)-one (5-12 a-b ) derivatives were synthesized, evaluated for their anticonvulsant activity against pentylenetetrazole (PTZ)-induced seizures and maximal electroshock test and compared with the reference drugs phenobarbital sodium and methaqualone. The neurotoxicity was assessed using rotarod test. The molecular docking was performed for all the synthesized compounds to assess their binding affinities to GABA-A receptor in order to rationalize their anticonvulsant activities in a qualitative way. The data obtained from the molecular modeling were correlated with those obtained from the biological screening. Compounds 9 a , 9 b , 12 a and 7 a showed the highest anticonvulsant activities of this series with relatively low neurotoxicity and low toxicity in the median lethal dose test when compared with the reference drugs. The obtained results proved that the most active compounds could be a useful model for future design, adaptation and investigation to construct more active analogs.ª 2015 Production and hosting by Elsevier B.V. on behalf

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Section: Rationale and Structure-based Designmentioning

confidence: 98%

Section: Rationale and Structure-based Designmentioning

confidence: 99%

Section: Log P Correlationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Design, synthesis, molecular docking and anticonvulsant evaluation of novel 6-iodo-2-phenyl-3-substituted-quinazolin-4(3H)-ones

Ibrahim

El‐Adl

Al‐Karmalawy

2015

Bulletin of Faculty of Pharmacy, Cairo University

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“…GI irritation, ulceration, dyspepsia and bleeding are common side effects of NSAIDS therapy. The treatment options which can be used for inflammatory diseases are unsatisfactory and complicated due to their compromised efficacy and adverse effect profile (Zayed et al, 2014). As a result Morbidity and Mortality are major consequences of toxicity induced by NSAIDs (Bhandari et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Pharmacological Evaluation, Molecular Docking and in silico ADMET Prediction of Nitric Oxide Releasing Biphenyls as Anti-Inflammatory Agents

2017

J App Pharm Sci

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Various 2-(4'-methyl-N-phenyl substituted)-1,1'-biphenyl-2-ylcarboxamido-2-oxoethyl nitrate analogues were synthesized and evaluated for analgesic, anti-inflammatory, ulcerogenic activity and nitric oxide release study. Compounds VM-4, VM-6, VM-9, VM-10, VM-11 and VM-12 exhibited good analgesic and anti-inflammatory activity compared to standard drug diclofenac. The compounds also showed decreased gastro-intestinal ulcerogenicity and gastro-protective activity in histopathological studies resulting in absence of mucosal injury. All the synthesized compounds were found to have significant in vivo nitric oxide releasing activity. The molecular docking was performed to understand the binding mode of these compounds. Results of this stu dy indicated that these NO-NSAIDs may have affinity towards COX-2 active site which can further be explored for selective or non-selective inhibitors.

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Synthesis, Anticonvulsant Activity, and SAR Study of Novel 4‐Quinazolinone Derivatives

Noureldin

Kothayer

Lashine

et al. 2017

Archiv der Pharmazie

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Series of N-(4-substitutedphenyl)-4-(1-methyl (or 1,2-dimethyl)-4-oxo-1,2-dihydroquinazolin-3(4H)-yl)-alkanamides (5a-j) and 4-chloro-N'-((1-methyl (or 1,2-dimethyl)-4-oxo-1,2-dihydroquinazolin-3(4H)-yl)-alkaloyl)benzohydrazides (6a-f) were designed based on the previously reported essential structural features for anticonvulsant activity. Several amino acids were incorporated within the synthesized quinazolin-4(3H)-ones to improve their bioavailability and the anticonvulsant activity. Synthesis of the target compounds was accomplished in four steps starting from the reaction between N-methyl isatoic anhydride and the appropriate amino acid. Then, the carboxylic acid group was utilized to synthesize the required final structures. The new quinazolinone derivatives were evaluated for their anticonvulsant activity according to the Anticonvulsant Drug Development (ADD) Program protocol. All the 16 new quinazolinones exhibited good anticonvulsant activity; especially 5f, 5b, and 5c showed superior anticonvulsant activities in comparison to the reference drug, with ED values of 28.90, 47.38, and 56.40 mg/kg, respectively.

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Design, synthesis, and biological evaluation studies of novel quinazolinone derivatives as anticonvulsant agents

Cited by 32 publications

References 18 publications

Design, synthesis, molecular docking and anticonvulsant evaluation of novel 6-iodo-2-phenyl-3-substituted-quinazolin-4(3H)-ones

Design, synthesis, molecular docking and anticonvulsant evaluation of novel 6-iodo-2-phenyl-3-substituted-quinazolin-4(3H)-ones

Synthesis, Pharmacological Evaluation, Molecular Docking and in silico ADMET Prediction of Nitric Oxide Releasing Biphenyls as Anti-Inflammatory Agents

Synthesis, Anticonvulsant Activity, and SAR Study of Novel 4‐Quinazolinone Derivatives

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