Novel 6,8-dibromo-4(3H)quinazolinone derivatives of anti-bacterial and anti-fungal activities

Mohamed, Mosaad S.; Kamel, Mona M.; Kassem, E. M. M.; Abotaleb, Nageh; El‐Moez, Sherein I. Abd; Ahmed, Marwa F.

doi:10.1016/j.ejmech.2010.04.014

Cited by 88 publications

(43 citation statements)

References 9 publications

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“…Compounds 19,20, and 22 showed remarkable DHFR inhibitory potency, (IC 50 0.6, 0.2, and 0.1 μM, respectively), in comparison to MTX (IC 50 , 0.08 μM). Compounds 12,17,18,20, and 24 showed remarkable broad spectrum antitumor potency and considered to be the most active members in this study with median IC 50 values of 0.6, 0.6, 0.5, 0.6, and 0.7 μM, respectively. In general, the mono-bromo series proved to be more active than the di-bromo counterparts and the 3-(2-hydrazinyl-acetyl)-is more active than its 3-(acetohydrazide) isosters in the involved biological activities.…”

Section: Resultsmentioning

confidence: 99%

“…All of the tested compounds exhibited antitumor potency of various magnitudes. Compounds 12,17,18,20, and 24 showed remarkable broad spectrum antitumor potency and considered to be the most active members in this study with median IC 50 values of 0.6, 0.6, 0.5, 0.6, and 0.7 μM, respectively. Some compounds showed selectivity toward the used tumor cell lines, such as 8, 19, and 22 against Colon HCT-116 (0.5, 0.3, and 0.2 μM, respectively), 11 and 14 against Lung A-549 (0.7 and 0.8 μM, respectively).…”

Section: In Vitro Antitumor Screeningmentioning

confidence: 99%

“…Enzyme structure, starting coordinate of human dihydrofolate reductase (hDHFR) enzyme in tertiary complex with reduced nicotinamide adenine dinucleotide phosphate (NADPH) and MTX, code ID 1 DLS, was obtained from the Protein Data Bank of Brookhaven National Laboratory [25]. Compounds 7-25 were previously reported [17][18][19].…”

Section: Methodsmentioning

confidence: 99%

“…This literature search allowed the selection of compounds 7-25 ( Fig. 2), [17][18][19] which were resynthesized. The present study reports the DHFR inhibition activity of a series of 6-bromo-and 6,8-dibromoquinazolin-4(3H)-one analogs accommodating 3-acetohydrazide, its isosteric analog 3-(2-hydrazinyl-acetyl)-and 4-hydrazine functions.…”

Section: Introductionmentioning

confidence: 99%

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Dihydrofolate reductase (DHFR) inhibition and molecular modeling study of some 6-bromo- or 6,8-dibromo-quinazolin-4(3H)-ones

Abdelkhalek¹,

Ewida²,

El‐Messery³

et al. 2018

A J Physiol Biochem Pharmacol

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Objectives:The dihydrofolate reductase (DHFR) inhibitory activity of 6-bromo-and 6,8-dibromo-quinazolin-4(3H)-ones (7-25) were studied to define the structural features and requirements that enhance selectivity and specificity for the proper binding to the enzyme active site. Methods:Compounds 7-25 were tested for their in vitro DHFR inhibition. As an application of the use of DHFR inhibitors, in vitro antitumor activity using disease-oriented human cell lines assay was performed. Key findings: Compounds 19, 20, and 22 showed remarkable DHFR inhibitory activity, inhibitory concentration (IC 50 0.6, 0.2, and 0.1 μM, respectively). Compounds 12, 17, 18, 20, and 24 proved to be broad spectrum antitumor with median IC 50 values of 0.6, 0.6, 0.5, 0.6, and 0.7 μM, respectively. Molecular docking study results revealed that the active DHFR inhibitors 22 and 20 bind to DHFR with similar amino acid residues as methotrexate, especially Arg 28. Conclusions:The mono-bromo series proved to be more active than the di-bromo counterparts and the 3-(2-hydrazinyl-acetyl)-is more active than its 3-(acetohydrazide) isoster. The investigated compounds could be used as template model for further optimization. ARTICLE HISTORY

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Section: Resultsmentioning

confidence: 99%

Section: In Vitro Antitumor Screeningmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dihydrofolate reductase (DHFR) inhibition and molecular modeling study of some 6-bromo- or 6,8-dibromo-quinazolin-4(3H)-ones

Abdelkhalek¹,

Ewida²,

El‐Messery³

et al. 2018

A J Physiol Biochem Pharmacol

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“…Quinazoline derivatives, endowed with a broad spectrum of biological activities and therapeutic properties, have shown promise as anti-bacterial, anti-fungal, antitumor, anti-inflammatory, anti-virus and anti-rheumatic drugs (Agarwal et al 2009;Bedi et al 2004;Foote et al 2008;Mohamed et al 2010). Such promising potential allows quinazoline derivatives to become good candidates for further pharmaceutical applications.…”

mentioning

confidence: 99%

Multiparameter-Based Bioassay of 2-(4-Chlorophenyl)-4-(4-methoxyphenyl) Quinazoline, a Newly-Synthesized Quinazoline Derivative, Toward Microcystis aeruginosa HAB5100 (Cyanobacteria)

Zhao

Liu

et al. 2015

Bull Environ Contam Toxicol

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Quinazoline derivatives have wide biological activities and therapeutic properties, implying their potential for development and application on a large scale. In the present study, 2-(4-chlorophenyl)-4-(4-methoxyphenyl) quinazoline (CMQ), was selected to examine its effect on unicellular cyanobacteria, Microcystis aeruginosa by evaluating growth, physiological and molecular responses. Growth was inhibited by CMQ, with a 96 h EC 50 of 1.93 ± 0.19 mg L -1 . The up-regulated expression of prx was shown, reflecting that oxidative stress might be a toxic factor of CMQ. At higher concentrations of CMQ, the quantum yields of Y(II) and Y(NPQ) in photosystem II decreased seriously and Y(NO) increased sharply, and psbA gene encoding for D1 protein was over-expressed. These results demonstrated that high concentrations of CMQ had different inhibitory targets associated with photosystem electron transport and with sites beyond the electron transport chain, leading to severe toxicity.

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Synthesis and Antimicrobial Evaluation of Some New Cyclooctanones and Cyclooctane‐Based Heterocycles

Ali

Hosni

Ragab

et al. 2011

Archiv der Pharmazie

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The versatile synthon (E)-2-((dimethyl amino)methylene)cyclooctanone (2) was used as a key intermediate for the synthesis of cyclooctanones and cyclooctane-based heterocycles with pyrazole, isoxazole, pyrimidine, pyrazolopyrimidine, triazolopyrimidine and imidazopyrimidine derivatives via its reactions with several nitrogen nucleophiles. The newly synthesized compounds were screened in vitro for their antimicrobial activity against pathogenic microorganisms (Listeria monocytogenes, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans). Most of the tested compounds showed moderate to high antibacterial and antifungal effects against the tested pathogenic microorganisms. Among the synthesized compounds, 2-((p-sulfonamidophenyl)methylene)cyclooctanone (5) showed excellent activity against Listeria monocytogenes.

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Novel 6,8-dibromo-4(3H)quinazolinone derivatives of anti-bacterial and anti-fungal activities

Cited by 88 publications

References 9 publications

Dihydrofolate reductase (DHFR) inhibition and molecular modeling study of some 6-bromo- or 6,8-dibromo-quinazolin-4(3H)-ones

Dihydrofolate reductase (DHFR) inhibition and molecular modeling study of some 6-bromo- or 6,8-dibromo-quinazolin-4(3H)-ones

Multiparameter-Based Bioassay of 2-(4-Chlorophenyl)-4-(4-methoxyphenyl) Quinazoline, a Newly-Synthesized Quinazoline Derivative, Toward Microcystis aeruginosa HAB5100 (Cyanobacteria)

Synthesis and Antimicrobial Evaluation of Some New Cyclooctanones and Cyclooctane‐Based Heterocycles

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