Synthesis, Structural, and Theoretical Studies of Quinazoline-2,4-dione Derivatives

El‐Sheshtawy, Hamdy S.; Abdelmonsef, Aboubakr H.; Abboudy, Sayed M.; Younes, Ahmed Mohamed Mosallem; Taha, Mohamed; Hassan, M. A.

doi:10.1080/10406638.2017.1325747

Cited by 11 publications

(14 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The synthetic strategy pathway for synthesis of hydrazide 1 is reported earlier in previous works. [18][19][20][21] Then, compound 1 was used as starting material for synthesis of new compounds 2 to 8 as declared in Scheme 1. Furthermore, the new heterocyclic moiety pyrazole in compound 2 was prepared via Knorr pyrazole synthesis by treatment of compound 1 with β-di-ketone such as acetylacetone in 79% yield as reported in Scheme 2.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis, Characterization, Antibacterial Activity, and Computer-Aided Design of Novel Quinazolin-2,4-dione Derivatives as Potential Inhibitors Against Vibrio cholerae

El‐Naggar

Mohamed

Mosallam

et al. 2020

Evol Bioinform Online

Self Cite

View full text Add to dashboard Cite

Cholera is a bacterial disease featured by dehydration and severe diarrhea. It is mainly caused by alimentary infection with Vibrio cholerae. Due to the wide applicability of quinazolin-2,4-dione compounds in medicinal and pharmaceutical chemistry, a new series of N-containing heterocyclic compounds was synthesized. We used the in silico docking method to test the efficacy of quinazolin-2,4-dione compounds in the prevention of cholera in humans. The newly synthesized compounds showed strong interactions and good binding affinity to outer membrane protein OmpU. Moreover, the pharmacokinetic properties of the newly synthesized compounds, such as absorption, distribution, metabolic, excretion, and toxicity (ADMET), were predicted through in silico methods. Compounds with acceptable pharmacokinetic properties were tested as novel ligand molecules. The synthesized compounds were evaluated in vitro for their antibacterial activity properties against Gram-negative Escherichia coli O78 strain using the minimum inhibition concentration (MIC) method. Compounds 2 and 6 showed reproducible, effective antibacterial activity. Hence, our study concludes that the quinazolin-2,4-dione derivatives 1 to 8 may be used as promising drug candidates with potential value for the treatment of cholera disease.

show abstract

Section: Chemistrymentioning

confidence: 99%

Synthesis, Characterization, Antibacterial Activity, and Computer-Aided Design of Novel Quinazolin-2,4-dione Derivatives as Potential Inhibitors Against Vibrio cholerae

El‐Naggar

Mohamed

Mosallam

et al. 2020

Evol Bioinform Online

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the present study, 3-(4-acetyl-phenyl)-1H-quinazolin-2,4-dione 1 was utilized as a starting compound for the synthesis of the quinazolindione skeletons (2)(3)(4)(5)(6)(7)(8)(9). The computational methodologies like homology modeling, active site prediction, and virtual screening approach have been developed for hit identification against cancer.…”

Section: Resultsmentioning

confidence: 99%

“…The quinazolindione scaffold and its derivatives have gained a wide spectrum in the medicinal and pharmaceutical chemistry fields, due to their promising biological activities like antifungal, antibacterial, and anticancer …”

Section: Introductionmentioning

confidence: 99%

“…[6] Mutation in Rho7 protein was identified as possible pathogenic in patients with breast cancer cell lines (MCF-7) and hepatocellular cancer cell lines (HepG2). [5] The quinazolindione scaffold and its derivatives have gained a wide spectrum in the medicinal and pharmaceutical chemistry fields, [7][8][9] due to their promising biological activities like antifungal, antibacterial, and anticancer. [10][11][12] In view of the facts mentioned above and as a part of our efforts to synthesis of new anticancer drug candidates, [13,14] herein, several derivatives of quinazolindione analogues were synthesized and screened for their antiproliferative activity.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis, in vitro biological evaluation and in silico docking studies of new quinazolin‐2,4‐dione analogues as possible anticarcinoma agents

Abdelmonsef

Mosallam

2020

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

Today, cancer is considered as one of the major reasons of death in human beings worldwide. We reported herein the synthesis, anticancer activity, and in silico docking studies of a series of nine quinazolindione‐based scaffolds bearing pyrimidine, pyridine, pyran, and pyrazole moieties (1‐9) through Michael addition, Vilsmeier‐Haack, Claisen‐Schmidt, and nucleophilic addition reactions. The chemical structures of the newly prepared compounds were ascertained by means of their spectral analysis techniques like IR, 1H‐nuclear magnetic resonance (NMR), 13C‐NMR, mass spectroscopy, and elemental analysis. This work was conducted to investigate the implication of Rho7 protein in breast and hepatocellular cancer cells aggressively. MCF‐7 and HepG2 cells have been selected as models for the effect of protein expression on breast and hepatocellular cancers cell growth. All prepared compounds were biologically evaluated for their antiproliferative efficacy on hepatic cancer cell lines (HepG2) and breast cancer cell lines (MCF‐7); also, their effects on normal cell lines (BALB/3T3) were studied. Moreover, in silico molecular docking studies were studied for the compounds against the binding site of Homo sapiens Rho7 protein. The pharmacokinetic properties of the newer compounds were also evaluated using various computational tools. The compounds showed interesting interactions with satisfactory docking scores to the target Rho7; thus, they may act as promising potent drug candidates against cancer.

show abstract

“…as they exhibited anti-fungal, anti-malarial, anti-cancer, and anti-inflammatory activities (Gómez and Kouznetsov, 2013). Quinazolin-2,4-diones are such interesting structural cores that found to have significant attention in medicinal and pharmaceutical chemistry (Hassan et al, 2013a,b;El-Sheshtawy et al, 2017;Abdelmonsef and Mosallam, 2020;El-Naggar et al, 2020). Heterocycles bearing nitrogen such as azetidinone, pyrrole, oxazole, oxadiazole, thiazole, pyrazole, and thiazolidine scaffolds are reported to possess a broad spectrum of applications in medicinal, biological as well as pharmaceutical activities as anti-fungal, anti-bacterial, anti-tumor, and anti-inflammatory drugs (Tanitame et al, 2004;Dua et al, 2011;Sokolova et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Novel Quinazolin-2,4-Dione Hybrid Molecules as Possible Inhibitors Against Malaria: Synthesis and in silico Molecular Docking Studies

Abdelmonsef

Mohamed

El-Naggar

et al. 2020

Front. Mol. Biosci.

View full text Add to dashboard Cite

The research explores the synthesis of a series of novel hybrid quinazolin-2,4-dione analogs bearing acetyl/amide bridged-nitrogen heterocyclic moieties such as azetidinone, pyrrole, oxazole, oxadiazole, thiazole, pyrazole, and thiazolidine scaffolds 2-16. The newly synthesized compounds were structurally confirmed by means of IR, 1 H-NMR, 13 C-NMR, MS and elemental analysis. In addition, an in silico molecular docking analysis of new compounds and standard drug (Chloroquine) has been performed to analyze the binding modes of interaction to the putative active site of Plasmodium falciparum Dihydroorotate dehydrogenase (pfDHODH). Aiming to search for potentially better antimalarials, a modern approach has been undertaken to identify new quinazolin-2,4-dione derivatives targeting pfDHODH. The identification of antimalarial activity of the newly synthesized compounds by using experimental techniques is expensive and requires extensive pains and labor. The compound 11 showed the highest binding affinity against pfDHODH. Moreover, the electrostatic potential (ESP) of the docked molecules was also calculated. Further, the pharmacokinetic properties (ADMET) of the prepared compounds were predicted through in silico technique.

show abstract

Synthesis, Structural, and Theoretical Studies of Quinazoline-2,4-dione Derivatives

Cited by 11 publications

References 17 publications

Synthesis, Characterization, Antibacterial Activity, and Computer-Aided Design of Novel Quinazolin-2,4-dione Derivatives as Potential Inhibitors Against Vibrio cholerae

Synthesis, Characterization, Antibacterial Activity, and Computer-Aided Design of Novel Quinazolin-2,4-dione Derivatives as Potential Inhibitors Against Vibrio cholerae

Synthesis, in vitro biological evaluation and in silico docking studies of new quinazolin‐2,4‐dione analogues as possible anticarcinoma agents

Novel Quinazolin-2,4-Dione Hybrid Molecules as Possible Inhibitors Against Malaria: Synthesis and in silico Molecular Docking Studies

Contact Info

Product

Resources

About