Synthesis and biological evaluation of novel 1-(aryl-aldehyde-oxime)uracil derivatives as a new class of thymidine phosphorylase inhibitors

Zhao, Shuyue; Li, Ké; Jin, Yi

doi:10.1016/j.ejmech.2017.12.016

Cited by 14 publications

(8 citation statements)

References 35 publications

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“…as a result of their ease of synthesis, uracil derivatives are regarded as promising compounds in drug discovery. The pyrimidine core is an important pharmacophore moiety of biologically active natural and synthetic compounds that compete for the same binding sites [15] the most conmen biological activities of uracil derivatives in the last years application Antioxidan t [2], Anti-flamatory [16], Anticaner [17], Anti-leukemia [18], Antibacterial [19,20], anti-tumour [21], anti-angiogenesis [22] and Anti-diabetic [23].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, identification of some new tetrazoline, thiazolidin-4-one and imidazolidin-4-one derivatives and evaluation anticancer of their molecular docking and anti-oxidant experimental

AL-tamimi¹,

Al-Majidi²

2023

3C TIC

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In this study, a new series of 1,3-dimethyl-6-(amino aceto hydrazine) pyrimidine-2,4- dione-6-yl with 4-substituted benzyldehyde, The compound (1-5) was synthesized in a single pot that cyclization by the addition of sodium azide, 2-mercapto acid & 2-amino acetic acid to produce five-membered heterocyclic rings includes: tetrazoline-1yl (6-10), thiazolidin-4-one (11-15) and imidazolidin-4-one (16-20) derivatives respectively. These compounds were characterized using spectral methods [FTIR and 1HNMR, 13C-NMR for some of them] evaluations, measurements, and analyses of their physical qualities. Each molecule was evaluated for antioxidant activity in vitro to use the DPPH and phosphomolybdenum methods. When compared to the standard drug Ascorbic acid, (1-20) demonstrated promising antioxidant activity among the bioactive molecules synthesized. Furthermore, molecular docking against, substances showed superiority over the standard medication Exemestane in tests of the Aromatase enzyme.

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Section: Introductionmentioning

confidence: 99%

Synthesis, identification of some new tetrazoline, thiazolidin-4-one and imidazolidin-4-one derivatives and evaluation anticancer of their molecular docking and anti-oxidant experimental

AL-tamimi¹,

Al-Majidi²

2023

3C TIC

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“…Recently,6-substituted benzoxazole or benzimidazole derivatives have been developed as multi-kinasei nhibitors, including tyrosine and serine/threonine kinases. [36] In the quest to find better anti-angiogenic agents, and as ac ontinuation of our previous studies on anticancer drug discovery, [66][67][68][69][70][71][72][73] we designed af amily of compoundsc ontaining 6-arylurea-2-arylbenzoxazoles and 6-arylurea-2-arylbenzimidazoles, with the goal of findingn ew potent anticancer agents ( Figure 2). [65] The X-ray crystallographic elucidation of the complex between 1 and VEGFR-2 demonstrated that the 2-fluoro-5-(trifluoromethyl)phenyl moiety is buried in the hydrophobic pocket, and the benzimidazole ring occupies the adenine pocket, interacting with the Cys919 residue, while the central arylurea linker is bent towardt he "hinge" region of the receptor.T herefore, we speculated that the length of the urea linker can be shortened appropriatelyt ob etter match the active site ( Figure 2).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally,2 -arylbenzoxazole analogues exhibit av arietyo fb iological activities, especially antitumora ctivities, for example, compound CJM-126. [36] In the quest to find better anti-angiogenic agents, and as ac ontinuation of our previous studies on anticancer drug discovery, [66][67][68][69][70][71][72][73] we designed af amily of compoundsc ontaining 6-arylurea-2-arylbenzoxazoles and 6-arylurea-2-arylbenzimidazoles, with the goal of findingn ew potent anticancer agents ( Figure 2). Allthe synthesized compounds were evaluated in vitro for inhibition of H1975, A549, and HeLa cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

Discovery of 6‐Arylurea‐2‐arylbenzoxazole and 6‐Arylurea‐2‐arylbenzimidazole Derivatives as Angiogenesis Inhibitors: Design, Synthesis and in vitro Biological Evaluation

Liu

et al. 2019

ChemMedChem

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We embarked on as tructuralo ptimization campaign aimed at the discoveryo fn ovel anti-angiogenesis agents with previously reported imidazole kinase inhibitors as al ead compound. A library of 29 compounds was synthesized.S everal title compounds exhibited selective inhibitory activities against vascular endothelial growth factor receptor 2( VEGFR-2) over epidermal growth factor receptor( EGFR) kinase;t hese compounds also displayed selective and potent antiproliferative activity against three cancerc ell lines. The newly synthesized compounds were evaluated for anti-angiogenesis activity by chick chorioallantoic membrane( CAM) assay.A mong them, 1-(2-(2-chloro-phenyl)benzo[d]oxazol-5-yl)-3-(4-(trifluoromethoxy)phenyl)urea (compound 5n)s howedt he most potent anti-angiogenesis capacity,e fficient cytotoxic activities (in vitro against humanu mbilical vein endothelial cells (HUVEC), H1975, A549, and HeLa cell lines, with respectiveI C 50 valueso f8 .46, 1.40, 7.61, and 0.28 mm), and an acceptable level of VEGFR-2 kinase inhibition (IC 50 = 0.25 mm). Molecular docking analysisr evealed 5n to be at ype II inhibitor of VEGFR-2 kinase. In general, these results indicatet hat these 6-arylurea-2-arylbenzoxazole/benzimidazole derivatives are promisingi nhibitors of VEGFR-2 kinase for potentiald evelopment into anti-angiogenesis drugs.

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“…Since prolonged treatment of cancer patients with same TPase inhibitors could lead to menacing side effects such as toxicity and resistance and hence to address such problems, a novel class of TPase inhibitors, 1‐(arylaldehyde oxime)uracil derivatives were designed (Zhao, Li, Jin, & Lin, ). The amidoxime structural unit of the 1‐(arylaldehyde oxime)uracil derivatives was presumed to have binding interactions with active catalytic sites (Phe210, Try168, Arg171, Lys190, Ser186, and His85).…”

Section: Introductionmentioning

confidence: 99%

“…1.34 | 1-(Arylaldehyde oxime)uracil derivatives Since prolonged treatment of cancer patients with same TPase inhibitors could lead to menacing side effects such as toxicity and resistance and hence to address such problems, a novel class of TPase inhibitors, 1-(arylaldehyde oxime)uracil derivatives were designed(Zhao, Li, Jin, & Lin, 2018). The amidoxime structural unit of the…”

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confidence: 99%

Evolution of uracil based thymidine phosphorylase inhibitors, SAR and electronic correlation: revisit

Dorababu¹

2019

Drug Development Research

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Thymidine phosphorylase (TPase), a dimeric proteinaceous enzyme is responsible for elevation of drug resistance and cell apoptosis. Increased TPase levels lead to angiogenesis which is a major culprit for the metastasis and cancer in the body. Hence, an efficient approach for anticancer drug discovery is based up on inhibition of thymidine phosphorylase enzyme. Solving of the crystal structure of TPase made the drug discovery easier. Legion of drugs was designed and synthesized having a wide variety of structural moieties and different functionalities such as phosphonic acid, amines, arylamines, acetamides, benzoyl, esters, amides, and so forth. Among the structural designs and models engineered, uracil is one of the structural motifs utilized for drug design. In this review, uracil is chosen where in structural unit with its structural modifications were summarized. Uracil unit could be structurally modified at its N1, N3, C5, and C6 positions to afford innumerable uracil derivatives. In general consensus, N1‐ and N3‐substituted uracil derivatives resulted in diminished/lower inhibitory activities which might be attributed to reduced acidic character. Whereas, substitution at 5‐ and 6‐positions have yielded fruitful results and excellent thymidine phosphorylase inhibitors prevailed. Furthermore, uracil possessing nucleoside uridine/deoxyuridine was also derivatized to afford potential TPase inhibitors. 3′‐ & 5′‐Hydroxyl groups of uridine/deoxyuridine were also exploited for derivative preparation and some of them were found to be potent TPase inhibitors.

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Synthesis and biological evaluation of novel 1-(aryl-aldehyde-oxime)uracil derivatives as a new class of thymidine phosphorylase inhibitors

Cited by 14 publications

References 35 publications

Synthesis, identification of some new tetrazoline, thiazolidin-4-one and imidazolidin-4-one derivatives and evaluation anticancer of their molecular docking and anti-oxidant experimental

Synthesis, identification of some new tetrazoline, thiazolidin-4-one and imidazolidin-4-one derivatives and evaluation anticancer of their molecular docking and anti-oxidant experimental

Discovery of 6‐Arylurea‐2‐arylbenzoxazole and 6‐Arylurea‐2‐arylbenzimidazole Derivatives as Angiogenesis Inhibitors: Design, Synthesis and in vitro Biological Evaluation

Evolution of uracil based thymidine phosphorylase inhibitors, SAR and electronic correlation: revisit

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