Novel 4(3H)-quinazolinone analogs: synthesis and anticonvulsant activity

El‐Azab, Adel S.; Abdel-Hamide, Sami G.; Sayed‐Ahmed, Mohamed M.; Hassan, Ghada S.; El-Hadiyah, Tariq M.; Al‐Shabanah, Othman A.; Al‐Deeb, Omar A.; El‐Subbagh, Hussein I.

doi:10.1007/s00044-012-0280-y

Cited by 57 publications

(56 citation statements)

References 12 publications

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“…Methaqualone 15 as a quinazoline analog is an important landmark in the field of synthetic anticonvulsants (Kashaw et al, 2009). The modification of 15 was carried out by El-Azab et al (2013) to obtain quinazolinone scaffold 16 which proved to be 2-fold more active than anticonvulsant drug sodium valproate. According to the findings of El-Azab and El- …”

Section: The Outcome Of Mes and Ptz Screening Carried Out On N-(submentioning

confidence: 99%

Quinazoline pharmacophore in therapeutic medicine

Ajani

Aderohunmu

Umeokoro

et al. 2016

Bangladesh J Pharmacol

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This present study comprehensively expatiates the functionalized utilization of quinazoline scaffolds in drug development and furnishes latest updates in pharmacological appositeness of its derivatives in order to reveal novel pathways for therapeutic targets. It traverses numerous biological potentials of quinazoline in the contemporary time to allow researchers' unhindered access to the beneficial role of quinazoline in fighting infectious diseases for future drug discovery. This work provides broad overview of medicinal survey of quinazoline chemistry valuable in the discovery of more efficient clinical trials and to summarize the most promising molecular targets for drug design. Article Info

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Section: The Outcome Of Mes and Ptz Screening Carried Out On N-(submentioning

confidence: 99%

Quinazoline pharmacophore in therapeutic medicine

Ajani

Aderohunmu

Umeokoro

et al. 2016

Bangladesh J Pharmacol

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“…Silica gel (60-230 mesh) was employed for routine column chromatography separations. Compounds 1-3 and 5 were prepared according to our previous report 25 , while compounds 4 and 17 were reported by Kennewell et al 26 and Zhao 28 .…”

Section: Chemistrymentioning

confidence: 99%

“…Synthesis of 2-mercapto-6-methyl-3-phenylquinazolin-4(3H)-one as starting material in 90% yield was achieved by the reaction of 5-methylanthranilic acid with 2-phenylisothiocyanate in absolute ethanol 25 . 2-Mercapto-6-methyl-3-phenylquinazolin-4(3H)-one was reacted with ethyl 2-bromoacetate in dry acetone in the presence of potassium carbonate at room temperature to afford ethyl 2-[(6-methyl-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl) thio]acetate (1) in 95% yield, and the latter compound was heated with hydrazine hydrate in ethanol to furnish 2-[(6-methyl-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio]acetohydrazid (2) in 90% yield.…”

Section: Chemistrymentioning

confidence: 99%

“…Such medical health problems have encouraged many medicinal chemists to search for novel antibacterial agents other than the analogs of existing antibiotics 7 . Quinazolines are frequently used in medicine because of their wide spectrum of biological activities [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] . Based on the good performances of quinazoline derivatives in anticancer application, development of novel quinazoline derivatives as anticancer drugs is a promising field 9 .…”

Section: Introductionmentioning

confidence: 99%

“…Based on aforementioned rational and our studies on quinazoline derivatives as attractive candidates for antitumor 9,[23][24][25] and antimicrobial agents 10,11,21 , we have designed a number of new quinazoline derivatives containing a 3-phenyl substituent attached with different fragments at 2-position to identify the dual antitumor and antimicrobial activities. Moreover, an in silico study, ADME-T prediction and molecular docking studies were used to identify the structural features required for the antitumor properties of the designed compounds.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, antitumor and antimicrobial activity of some new 6-methyl-3-phenyl-4(3H)-quinazolinone analogues: in silico studies

Alanazi

Abdel‐Aziz

Shawer

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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Some new derivatives of substituted-4(3H)-quinazolinones were synthesized and evaluated for their in vitro antitumor and antimicrobial activities. The results of this study demonstrated that compound 5 yielded selective activities toward NSC Lung Cancer EKVX cell line, Colon Cancer HCT-15 cell line and Breast Cancer MDA-MB-231/ATCC cell line, while NSC Lung Cancer EKVX cell line and CNS Cancer SF-295 cell line were sensitive to compound 8. Additionally, compounds 12 and 13 showed moderate effectiveness toward numerous cell lines belonging to different tumor subpanels. On the other hand, the results of antimicrobial screening revealed that compounds 1, 9 and 14 are the most active against Staphylococcus aureus ATCC 29213 with minimum inhibitory concentration (MIC) of 16, 32 and 32 mg/mL respectively, while compound 14 possessed antimicrobial activities against all tested strains with the lowest MIC compared with other tested compounds. In silico study, ADME-Tox prediction and molecular docking methodology were used to study the antitumor activity and to identify the structural features required for antitumor activity.

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Structural Exploration of Quinazolin‐4(3H)‐ones as Anticonvulsants: Rational Design, Synthesis, Pharmacological Evaluation, and Molecular Docking Studies

Ugale

Bari

2016

Archiv der Pharmazie

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Anticonvulsants effective against multiple seizures are of wide interest as antiepileptic drugs, especially if active against pharmaco-resistant seizures. Herein, we synthesized 16 different, rationally designed 2-((6,7-dimethoxy-4-oxo-2-phenylquinazolin-3(4H)-yl)amino)-N-(substituted phenyl)acetamides and screened for anticonvulsant activities through in vivo experiments. Compound 4d emerged as prototype with excellent anti-seizure action in mice against electroshock, chemically induced and pharmaco-resistant 6-Hz seizure models with no symptoms of neurotoxicity and hepatotoxicity (ED = 23.5 mg/kg, MES, mice, i.p.; ED = 32.6 mg/kg, scPTZ, mice, i.p.; ED = 45.2 mg/kg, 6-Hz, mice, i.p.; TD = 325.9 mg/kg, mice, i.p.). In addition, investigation of compound 4l in mice for its pharmacological profile proved it as safer anticonvulsant, devoid of the side effects such as motor dysfunction and hepatotoxicity of classical antiepileptic drugs (ED = 26.1 mg/kg, MES, mice, i.p.; ED = 79.4 mg/kg, scPTZ, mice, i.p.; TD = 361.2 mg/kg, mice, i.p.). We also predicted physiochemical and pharmacokinetic properties of structurally optimized quinazolin-4(3H)-ones by a computational protocol. A combination of in vivo anticonvulsant profile, ex vivo toxicity, and in silico studies suggested that the synthesized compounds may be useful as broad-spectrum anti-seizure drug candidates with favorable pharmacokinetic parameters.

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Novel 4(3H)-quinazolinone analogs: synthesis and anticonvulsant activity

Cited by 57 publications

References 12 publications

Quinazoline pharmacophore in therapeutic medicine

Quinazoline pharmacophore in therapeutic medicine

Synthesis, antitumor and antimicrobial activity of some new 6-methyl-3-phenyl-4(3H)-quinazolinone analogues: in silico studies

Structural Exploration of Quinazolin‐4(3H)‐ones as Anticonvulsants: Rational Design, Synthesis, Pharmacological Evaluation, and Molecular Docking Studies

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