Synthesis of Novel Analogs of Thieno[2,3-d] Pyrimidin-4(3H)-ones as Selective Inhibitors of Cancer Cell Growth

Zhang, Sheng; Liu, Feize; Hou, Xueling; Cao, Ji; Dai, Xiling; Yu, Junjie; Huang, Guozheng

doi:10.3390/biom9100631

Cited by 9 publications

(5 citation statements)

References 38 publications

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“…Lung cancer is a major public health problem worldwide, while non-small cell lung cancer (NSCLC) represents about 80-90% of all cases (49)(50)(51)(52)(53). Indeed, NSCLC has a high mortality rate, and the 5-year survival rate of these patients remain challenging (54)(55)(56)(57).…”

Section: Lung Cancermentioning

confidence: 99%

Emerging Roles and Mechanisms of lncRNA FOXD3-AS1 in Human Diseases

2022

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Numerous long noncoding RNAs (lncRNAs) have been identified as powerful regulators of human diseases. The lncRNA FOXD3-AS1 is a novel lncRNA that was recently shown to exert imperative roles in the initialization and progression of several diseases. Emerging studies have shown aberrant expression of FOXD3-AS1 and close correlation with pathophysiological traits of numerous diseases, particularly cancers. More importantly, FOXD3-AS1 was also found to ubiquitously impact a range of biological functions. This study aims to summarize the expression, associated clinicopathological features, major functions and molecular mechanisms of FOXD3-AS1 in human diseases and to explore its possible clinical applications.

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Section: Lung Cancermentioning

confidence: 99%

Emerging Roles and Mechanisms of lncRNA FOXD3-AS1 in Human Diseases

2022

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“…The derivatives 187 and 188 displayed the highest affinity towards DNA, whereas (IC 50 : 135.5 μM) were found to inhibit tyrosine kinase efficiently. 233 Later, Zhang et al 234 in 2019 synthesized a series of disubstituted thienopyrimidinones and evaluated for their cancer cell growth inhibition against A549, PC-3, MCF-7, PC-9, and HL-7702 cancer cell lines. Amongst the derivatives, 191 (Figure 26; IC 50 : 0.94 µM) was found to be the most potent molecule against A549 cell lines, without any toxicity towards the healthy human liver cells.…”

Section: Thienopyrimidinementioning

confidence: 99%

“…Thus 191 can be further investigated as a potential chemotherapeutic representative in lung cancer therapy. 234 However, during the same time, Mghwary et al, 235 prepared a series of novel 4-substituted-tetrahydrocycloheptathienopyrimidine derivatives, which were tested for their antiproliferative activity against MCF-7 cancer cell lines. Among the analogs, compound 192 (IC 50 : 0.66 ± 0.05 µM) exhibited the most potent cytotoxicity, which was 1.73 and 4.64 folds more potent than that of the reference drugs erlotinib (IC 50 : 3.06 ± 0.19 µM) and doxorubicin (IC 50 : 1.14 ± 0.05 µM).…”

Section: Thienopyrimidinementioning

confidence: 99%

“…This compound was also subjected to western blot analysis and enzymatic activity experiments, which established that it activated caspase‐3 activity through upregulating Bax and reducing the level of Bcl‐2 expression, thus inducing apoptosis of A549 cells. Thus 191 can be further investigated as a potential chemotherapeutic representative in lung cancer therapy 234 . However, during the same time, Mghwary et al, 235 prepared a series of novel 4‐substituted‐tetrahydrocycloheptathienopyrimidine derivatives, which were tested for their antiproliferative activity against MCF‐7 cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

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Expedition of sulfur‐containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update

Laxmikeshav

Kumari

Shankaraiah

2021

Medicinal Research Reviews

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This review article proposes a comprehensive report of the design strategies engaged in the development of various sulfur-bearing cytotoxic agents. The outcomes of various studies depict that the sulfur heterocyclic framework is a fundamental structure in diverse synthetic analogs representing a myriad scope of therapeutic activities. A number of five-, six-and seven-membered sulfur-containing heterocyclic scaffolds, such as thiazoles, thiadiazoles, thiazolidinediones, thiophenes, thiopyrans, benzothiazoles, benzothiophenes, thienopyrimidines, simple and modified phenothiazines, and thiazepines have been discussed. The subsequent studies of the derivatives unveiled their cytotoxic effects through multiple mechanisms (viz. inhibition of tyrosine kinases, topoisomerase I and II, tubulin, COX, DNA synthesis, and PI3K/Akt and Raf/MEK/ERK signaling pathways), and several others. Thus, our concise illustration explains the design strategy and anticancer potential of these five-and six-membered sulfur-containing heterocyclic molecules along with a brief outline on seven-membered sulfur heterocycles. The thorough assessment of antiproliferative activities with the reference drug allows a proficient assessment of the structure-activity relationships (SARs) of the diversely synthesized molecules of the series.

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“…Research in the field of ligand-based design led to the discovery of the thienopyrimidine derivatives apitolisib and CUDC-907 inhibiting PI3K kinase and mTOR kinase [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

2-Alkyl-Substituted-4-Amino-Thieno[2,3-d]Pyrimidines: Anti-Proliferative Properties to In Vitro Breast Cancer Models

Iliev,

Mavrova,

Yancheva

et al. 2023

Molecules

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Thienopyrimidines are structural analogs of quinazolines, and the creation of new 2-alkyl derivatives of ethyl 4-aminothienopyrimidine-6-carboxylates for the study of their anti-proliferative properties is of great pharmacological interest. Some 2-alkyl-4-amino-thieno[2,3-d]pyrimidines 2–5 were synthesized, and their cyto- and phototoxicity against BALB 3T3 cells were established by an in vitro 3T3 NRU test. The obtained results indicate that the tested compounds are not cytotoxic or phototoxic, and that they are appropriate to be studied for their anti-proliferative and anti-tumor properties. The anti-proliferative potential of the compounds was investigated on MCF-7 and MDA-MB-231 cancer cells, as well as a MCF-10A cell line (normal human mammary epithelial cells). The most toxic to MCF-7 was thienopyrimidine 3 with IC50 13.42 μg/mL (IC50 0.045 μM), followed by compound 4 (IC50 28.89 μg/mL or IC50 0.11 μM). The thienopyrimidine 4 revealed higher selectivity to MCF-7 and lower activity (IC50 367 μg/mL i.e., 1.4 μM) than compound 3 with MCF-10A cells. With respect to MDA-MB-231 cells, ester 2 manifested the highest effect with IC50 52.56 μg/mL (IC50 0.16 μM), and 2-ethyl derivative 4 revealed IC50 62.86 μg/mL (IC50 0.24 μM). It was estimated that the effect of the substances on the cell cycle progression was due to cell cycle arrest in the G2 stage for MDA-MB-231, while arrest in G1 was detected for the estrogen (ER)-positive MCF-7 cell line. The tested compound’s effects on the change of the zeta potential in the tumorigenic cells utilized in this study were determined. The calculation which we performed of the physicochemical properties and pharmacokinetic parameters influencing the biological activity suggested high intestinal absorption, as well as drug-likeness.

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Synthesis of Novel Analogs of Thieno[2,3-d] Pyrimidin-4(3H)-ones as Selective Inhibitors of Cancer Cell Growth

Cited by 9 publications

References 38 publications

Emerging Roles and Mechanisms of lncRNA FOXD3-AS1 in Human Diseases

Emerging Roles and Mechanisms of lncRNA FOXD3-AS1 in Human Diseases

Expedition of sulfur‐containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update

2-Alkyl-Substituted-4-Amino-Thieno[2,3-d]Pyrimidines: Anti-Proliferative Properties to In Vitro Breast Cancer Models

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