Synthesis, single-crystal, in vitro antitumor evaluation and molecular docking of 3-substitued 5,5-diphenylimidazolidine-2,4-dione derivatives

Alanazi, Amer M.; El‐Azab, Adel S.; Alswaidan, Ibrahim A.; Maarouf, Azza R.; El‐Bendary, Eman R.; El-Enin, Mohamed A. Abu; Abdel‐Aziz, Alaa A.‐M.

doi:10.1007/s00044-013-0597-1

Cited by 33 publications

(15 citation statements)

References 49 publications

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“…Compound 1 and 5-(4-methylpyridin-2-yl)-1H-pyrazole-3-carboxylic acid for compound 2 were prepared using literature procedures. 54–55 Morpholine intermediates were purchased or prepared using two methods. Compound 2 and the analogs were prepared by amide coupling of 5-(4-methylpyridin-2-yl)-1H-pyrazole-3-carboxylic acid and the corresponding morpholines.…”

Section: Methodsmentioning

confidence: 99%

Two distinct mechanisms of small molecule inhibition of LpxA acyltransferase essential for lipopolysaccharide biosynthesis

Han¹,

Ma²,

Balibar³

et al. 2019

Preprint

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Section: Methodsmentioning

confidence: 99%

Two distinct mechanisms of small molecule inhibition of LpxA acyltransferase essential for lipopolysaccharide biosynthesis

Han¹,

Ma²,

Balibar³

et al. 2019

Preprint

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“…Compound 1 and 5-(4-methylpyridin-2-yl)-1H-pyrazole-3-carboxylic acid for compound 2 were prepared by literature procedures [17][18] . When morpholine intermediates were not commercially available, they were prepared by two different methods [19][20] .…”

Section: Chemical Synthesismentioning

confidence: 99%

Two distinct mechanisms of small molecule inhibition of LpxA acyltransferase essential for lipopolysaccharide biosynthesis

Han

Balibar

et al. 2019

Preprint

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This PDF file includes:Supplementary Methods Figs. S1 to S5 Tables S1 to S3 Supplementary Information Text Bacterial strains, plasmids, routine growth condition, and compound susceptibility testBacterial strains and plasmids used in this study are listed in Table S1. Miller's lysogeny broth (LB) 1 and LB-agar were used for routine growth and bacterial selection during plasmid construction. To maintain plasmids, 100 µg/mL ampicillin (Ap), 10 µg/mL chloramphenicol (Cm), and 50 µg/mL kanamycin (Km) were added to the media as needed. Compound susceptibility testing to determine MICs was performed in cation adjusted Mueller-Hinton II broth (CAMHB) according to CLSI protocols, as described previously 2 . To induce genes under the control of a lac promoter, 100 µM isopropyl β-D-1-thiogalactopyranoside (IPTG) was added to the media used in susceptibility testing. Compounds were synthesized at Novartis as described below. CHIR-090 was purchased from ChemScene (CS-0973). Spontaneous mutant selectionFor mutant selection with compound 1, cells in overnight culture of MG1655 ΔtolC were spread on LB agar containing 0.5 µg/mL compound 1. For mutant selection with compound 14, overnight culture of CDY0154 was used and the cells were spread on L-agar containing 16 and 32 µg/mL compound 14. Serial dilutions of the overnight culture were spread on LB agar to determine the number of cells (approximately 10 8 and 10 9 cells) used for selection. The LB agar plates were incubated overnight at 37 °C. Colonies arose and were streaked on fresh LB agar. After incubation overnight at 37 °C, a single colony of each mutant was grown in LB and stored in 15% glycerol at -80 °C for genome sequencing and susceptibility tests. The fabZ mutants were isolated from selection with inhibitors of LpxA and LpxD. Genome sequencing and mutation confirmationGenomic DNA for whole genome sequencing was isolated from E. coli strains using the Qiagen DNeasy Blood and Tissue kit with following the instruction for Gram-negative bacterial DNA. To sequence the genomes of isolated mutants, library preparation and sequencing reaction for next generation sequencing, and data analysis were performed using the Illumina Sample Preparation kits and Illumina Sequencer as described previously 2 . Sequencing reads were aligned to the reference E. coli MG1655 genome (Genbank ID: NC_000913.3) using bwa for determining single nucleotide polymorphisms and short insertion/deletions (indels, typically <10 bp). Mutations identified by genomics were confirmed by targeted PCR and Sanger sequencing. The primers were used to amplify the gene of interest with Phusion High-Fidelity PCR Master Mix with GC Buffer according to established protocols. Sequencing was performed by Elim BioPharma (Hayward, CA). The primers used for PCR and sequencing were TU117, TU243, TU276, TU332, TU475, TU503, TU504, TU512, and TU513. Construction of CDY0154The acrAB locus was replaced with the kanamycin resistant cassette (Km r ) using the λRED recombination system as described previously 3 . The DNA fragmen...

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“…Imidazolidine-2,4-dione (hydantoin) is a versatile scaffold that exerts a wide range of pharmacological effects such as anticancer activity and inhibition of COX-1/2 and carbonic anhydrase (Abdel-Aziz et al, 2016, Abdel-Aziz et al, 2015, Alanazi et al, 2013, Zuliani et al, 2009, Zhang et al, 2017, Azizmohammadi et al, 2013, Mostafa et al, 2016, Hmuda et al, 2014). A 5,5-diphenylimidazolidine-2,4-dione derivative ( I ) displayed a promising growth inhibitory activity against several distinct cancer cell lines at 10 μM (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…A 5,5-diphenylimidazolidine-2,4-dione derivative ( I ) displayed a promising growth inhibitory activity against several distinct cancer cell lines at 10 μM (Fig. 1) (Alanazi et al, 2013). The proposed molecular mechanism of anticancer activity was mediated by EGFR kinase inhibition (Alanazi et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, anticancer, apoptosis-inducing activities and EGFR and VEGFR2 assay mechanistic studies of 5,5-diphenylimidazolidine-2,4-dione derivatives: Molecular docking studies

Alkahtani

Alanazi

Aleanizy

et al. 2019

Saudi Pharmaceutical Journal

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A new series of 5,5-diphenylhydantoin derivatives containing benzylidene or isatin (4–19) was synthesized. Their anticancer activity against HeLa, a cervical cancer cell line, A549, a lung cancer cell line, and MDA-MB-231, a breast cancer cell line, was evaluated. Compounds 13, 16, 17 and 18 exhibited potent anticancer activity with average IC50 values against the tested cell lines of 109, 59, 81 and 113 μM, respectively. Compound 16 showed potent EGFR and VEGFR2 inhibitory activity with IC50 values of 6.17 and 0.09 μM, respectively. In addition, compound 16 induced caspase-dependent apoptosis and reactive oxygen species (ROS) production at 5 and 10 μM. Moreover, a molecular docking simulation was performed for compound 16 and sunitinib to predict the protein-ligand interactions with the active site of VEGFR2.

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Synthesis, single-crystal, in vitro antitumor evaluation and molecular docking of 3-substitued 5,5-diphenylimidazolidine-2,4-dione derivatives

Cited by 33 publications

References 49 publications

Two distinct mechanisms of small molecule inhibition of LpxA acyltransferase essential for lipopolysaccharide biosynthesis

Two distinct mechanisms of small molecule inhibition of LpxA acyltransferase essential for lipopolysaccharide biosynthesis

Two distinct mechanisms of small molecule inhibition of LpxA acyltransferase essential for lipopolysaccharide biosynthesis

Synthesis, anticancer, apoptosis-inducing activities and EGFR and VEGFR2 assay mechanistic studies of 5,5-diphenylimidazolidine-2,4-dione derivatives: Molecular docking studies

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