Novel Aminopyrimidine-2,4-diones, 2-Thiopyrimidine-4-ones, and 6-Arylpteridines as Dual-Target Inhibitors of BRD4/PLK1: Design, Synthesis, Cytotoxicity, and Computational Studies.

Structural-based drug design and solvent-free synthesis were combined to obtain three novel series of 5-arylethylidene-aminopyrimidine-2,4-diones (, -, ,), 5-arylethylidene-amino-2-thiopyrimidine-4-ones (,), and 6-arylpteridines (,) as dual BRD4 and PLK1 inhibitors. MTT assays of synthesized compounds against breast (MDA-MB-231), colorectal (HT-29), and renal (U-937) cancer cells showed excellent-to-good cytotoxic activity, compared to Methotrexate; MDA-MB-231 were the most sensitive cancer cells. The most active compounds were tested against normal Vero cells.

Design and synthesis of new spirooxindole candidates and their selenium nanoparticles as potential dual Topo I/II inhibitors, DNA intercalators, and apoptotic inducers.

A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation of spirooxindoles and pyrimidines. selenium nanoparticles (SeNPs) for some derivatives were synthesised. The targets and the SeNP derivatives were examined for their cytotoxicity towards five cancer cell lines.

Design, Synthesis, and Biological Evaluation of New Potential Unusual Modified Anticancer Immunomodulators for Possible Non-Teratogenic Quinazoline-Based Thalidomide Analogs.

Sixteen new thalidomide analogs were synthesized. The new candidates showed potent in vitro antiproliferative activities against three human cancer cell lines, namely hepatocellular carcinoma (HepG-2), prostate cancer (PC3), and breast cancer (MCF-7). It was found that compounds XII, XIIIa, XIIIb, XIIIc, XIIId, XIVa, XIVb, and XIVc showed IC values ranging from 2.

Discovery of New Uracil and Thiouracil Derivatives as Potential HDAC Inhibitors.

: Histone deacetylase inhibitors (HDACIs) are a relatively new class of potential drugs for treating cancer. : Discovery of new anticancer agents targeting HDAC. : New uracil and thiouracil derivatives panels were designed and synthesized as HDAC inhibitors.

New thiouracil derivatives as histone deacetylase inhibitors and apoptosis inducers: design, synthesis and anticancer evaluation.

Histone deacetylase (HDAC) inhibitors have good contributions in cancer management. To introduce new active HDAC inhibitors. Design and synthesis of 16 thiouracil derivatives with deep biological and computational investigation.

Novel pyrimidine Schiff bases and their selenium-containing nanoparticles as dual inhibitors of CDK1 and tubulin polymerase: design, synthesis, anti-proliferative evaluation, and molecular modelling.

Nanotechnology-based strategies can overcome the limitations of conventional cancer therapies. Hence, novel series of pyrimidine Schiff bases () were employed in the synthesis of selenium nanoparticle forms (). All selenium nano-sized forms exerted greater inhibitions than normal-sized compounds, far exceeding 5-fluorouracil activity.

Design and synthesis of novel uracil-linked Schiff bases as dual histone deacetylase type II/topoisomerase type I inhibitors with apoptotic potential.

The previously reported dual histone deacetylase type II (HDAC II) / topoisomerase type I (Topo I) inhibitors suffer pharmacokinetic limitations because of their huge molecular weights. We report the design and synthesis of a smarter novel set of uracil-linked Schiff bases () as dual HDAC II/Topo I inhibitors keeping the essential pharmacophoric features. Cytotoxicity of all compounds was assessed against three cancer cell lines.

Design, Synthesis, and Anti-Proliferative Action of Purine/Pteridine-Based Derivatives as Dual Inhibitors of EGFR and BRAF.

The investigation of novel EGFR and BRAF dual inhibitors is intended to serve as targeted cancer treatment. Two sets of purine/pteridine-based derivatives were designed and synthesized as EGFR/BRAF dual inhibitors. The majority of the compounds exhibited promising antiproliferative activity on the cancer cell lines tested.

Synthesis and study of pyrimidine-phthalimide hybrids as VEGFR2 inhibitors with antiproliferative activity.

Thalidomide, a once notorious sedative, is now clinically used as an antitumor agent. We aimed to use it as a lead compound for designing pyrimidine-phthalimide hybrids. Nucleophilic substitution reaction of thalidomide analog with primary and/or secondary aliphatic amines afforded pyrimidine-phthalimide hybrids , and .

Design and synthesis of uracil/thiouracil based quinoline scaffolds as topoisomerases I/II inhibitors for chemotherapy: A new hybrid navigator with DFT calculation.

In this work, a novel promising hybrid mode of uracil/thiouracil based quinoline pharmacophore i.e. 5a-f was rationalized and synthesized based on rigidification and lipophilic principles, and following the reported pharmacophoric features of camptothecin & doxorubicin.

Synthesis, DFT calculations, and anti-proliferative evaluation of pyrimidine and selenadiazolopyrimidine derivatives as dual Topoisomerase II and HSP90 inhibitors.

Novel series of aminopyrimidines bearing a biologically active cyclohexenone and oxo-selaneylidene moiety , besides selenadiazolopyrimidines ( and ), were synthesised using 5,6-diaminouracils as starting materials. Compound exhibited strong anti-proliferative activity against three cell lines: HepG-2 (IC 14.31 ± 0.

Design, synthesis and antitumor activity of novel pyran-functionalized uracil derivatives: docking studies.

Synthesis of novel pyran-based uracils that may have potent antitumor activity against hepatocellular carcinoma HepG2 and ovarian cancer SKOV3 cell lines. Novel pyran-based uracils were synthesized and their anticancer activity was assessed using methyl thiazolyl tetrazolium and wound-healing assays to detect their cytotoxicity and their antiproliferative and antimigratory activities. Compounds , , , , , , , and significantly inhibited cell proliferation of the HepG2 cell line.

Synthesis, pharmacological evaluation, DFT calculation, and theoretical investigation of spirocyclohexane derivatives.

Polycyclic structures fused at a central carbon are of great interest due to their appealing conformational features and their structural implications in biological systems. Although progress in the development of synthetic methodologies toward such structures has been impressive, the stereo selective construction of such quaternary stereo centers remains a significant challenge in the total synthesis of natural products. From the computational calculations by Density Functional Theory along with the B3LYP as basis set, It is obvious that the all studied compounds are soft molecules and η varied from 0.

Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline-Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors.

A series of quinoline-uracil hybrids () has been rationalized and synthesized. The inhibitory activity against hCA isoforms I, II, IX, and XII was explored. Compounds demonstrated powerful inhibitory activity against all tested hCA isoforms.

One-Pot Synthesis and Molecular Modeling Studies of New Bioactive Spiro-Oxindoles Based on Uracil Derivatives as SARS-CoV-2 Inhibitors Targeting RNA Polymerase and Spike Glycoprotein.

The first outbreak in Wuhan, China, in December 2019 was reported about severe acute coronaviral syndrome 2 (SARS-CoV-2). The global coronavirus disease 2019 (COVID-19) pandemic in 2020 resulted in an extremely high potential for dissemination. No drugs are validated in large-scale studies for significant effectiveness in the clinical treatment of COVID-19 patients, despite the worsening trends of COVID-19.

Synthesis, In Silico Prediction and In Vitro Evaluation of Antimicrobial Activity, DFT Calculation and Theoretical Investigation of Novel Xanthines and Uracil Containing Imidazolone Derivatives.

Novel xanthine and imidazolone derivatives were synthesized based on oxazolone derivatives as a key intermediate. The corresponding xanthine and imidazolone derivatives were obtained via reaction of oxazolone derivative with 5,6-diaminouracils under various conditions. Xanthine compounds were obtained by cyclocondensation of 5,6-diaminouracils with different oxazolones in glacial acetic acid.

In vitro antimicrobial evaluation and in silico studies of coumarin derivatives tagged with pyrano-pyridine and pyrano-pyrimidine moieties as DNA gyrase inhibitors.

Several coumarin-containing substitute nitrogen heterocycles have recently received considerable importance due to their diverse pharmacological properties. One-pot and rapid synthesis of coumarin derivatives was achieved via reactions of acetyl-coumarin with p-chloro-benzaldehyde and malononitrile to provide compound 2-containing cyano-amine using conventional heating. Compound 2 was condensed with different carbon electrophiles triethyl orthoformate, phenyl isocyanate, carbon disulfide, benzoyl chloride, and acetyl chloride that afforded the corresponding chromene derivatives 3-17.

Synthesis, In Silico Prediction and In Vitro Evaluation of Antitumor Activities of Novel Pyrido[2,3-]pyrimidine, Xanthine and Lumazine Derivatives.

Ethyl 5-arylpyridopyrimidine-6-carboxylates - were prepared as a one pot three component reaction via the condensation of different aromatic aldehydes and ethyl acetoacetate with 6-amino-1-benzyluracil under reflux condition in ethanol. Additionally, condensation of ethyl 2-(2-hydroxybenzylidene) acetoacetate with 6-amino-1-benzyluracil in DMF afforded 6-acetylpyridopyrimidine-7-one ; a facile, operationally, simple and efficient one-pot synthesis of 8-arylxanthines - is reported by refluxing 5,6-diaminouracil with aromatic aldehydes in DMF. Moreover, 6-aryllumazines - was obtained via the reaction of 5,6-diaminouracil with the appropriate aromatic aldehydes in triethyl orthoformate under reflux condition.

Novel 2-Thioxanthine and Dipyrimidopyridine Derivatives: Synthesis and Antimicrobial Activity.

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Synthesis and anticancer evaluation of some novel pyrimido[5,4-e][1,2,4]triazines and pyrazolo[3,4-d]pyrimidine using DMF-DMA as methylating and cyclizing agent.

Background: Described a series of main target compounds pyrimido[5,4-e][1,2,4]triazines is obtained via condensation of 6-hydrazinyluracil with different aromatic aldehydes to give the hydrazones followed by nitrosation with HNO then intramolecular cyclization. On the other hand, pyrazolopyrimidines can be obtained by the reaction of hydrazones with dimethylformamide-dimethylacetal (DMF-DMA), DMF-DMA in the presence of DMF or by refluxing the hydrazinyluracil with DMF-DMA in the presence of DMF directly. The newly synthesized compounds are evaluated in vitro for their anticancer activity against human lung carcinoma (A549).

One pot synthesis, antimicrobial and antioxidant activities of fused uracils: pyrimidodiazepines, lumazines, triazolouracil and xanthines.

Background: Uracil derivatives have a great attraction because they play an important role in pharmacological activities. Pyrimidodiazepines, lumazines, triazolopyrimidines and xanthines have significant wide spectrum activities including anticancer, antiviral as well as antimicrobial activities.

Results: A newly synthesized compounds pyrimido[4,5-b][1, 4]diazepines 5a-e, 6a-d, lumazines 7a-d, triazolo[4,5-d]pyrimidine 8 and xanthines 9, 10 was prepared in a good yields.

A Novel Synthesis of Fused Uracils: Indenopyrimidopyridazines, Pyrimidopyridazines, and Pyrazolopyrimidines for Antimicrobial and Antitumor Evalution.

A variety of different compounds of fused uracils were prepared simply by the heating of 6-hydrazinyl-1-methyl-, 6-hydrazinyl-1-propyl-, or 6-hydrazinyl-1,3-dipropyluracil under reflux with ninhydrin, isatin, benzylidene malononitrile, benzylylidene ethyl cyanoacetate, benzil, and phenacyl bromide derivatives. The newly synthesized compounds were completely screened for antimicrobial and antitumor activity.

Novel 2-Thioxanthine and Dipyrimidopyridine Derivatives: Synthesis and Antimicrobial Activity.

Several fused imidazolopyrimidines were synthesized starting from 6-amino-1-methyl-2-thiouracil (1) followed by nitrosation, reduction and condensation with different aromatic aldehydes to give Schiff's base. The dehydrocyclization of Schiff's bases using iodine/DMF gave Compounds 5a-g. The methylation of 5a-g using a simple alkylating agent as dimethyl sulfate ((CH₃)₂SO₄) gave either monoalkylated imidazolopyrimidine 6a-g at room temperature or dialkylated derivatives 7a-g on heating 6a-g with ((CH₃)₂SO₄).

Synthesis, DNA binding and antiviral activity of new uracil, xanthine, and pteridine derivatives.

Some new 6-amino-1,3-dimethyl-5-(substituted methylidene)aminouracils were synthesized. Most of them were cyclized with triethyl orthoformate as a one-carbon source to afford 1,3-dime-thyl-6-substituted pteridine derivatives. Certain uracils gave xanthine instead of the expected pteridine derivatives upon using another one-carbon source such as triethyl orthoacetate or triethyl orthobenzoate.