Design, synthesis, and anti-breast-cancer activity evaluation of pyrrolo(pyrido)[2,3-d]pyrimidine derivatives

Ding, Jie; Liu, Tao; Zeng, Changguang; Li, Bingqing; Ai, Yi; Zhang, Xiaohan; Zhong, Hang

doi:10.1007/s10593-022-03110-w

Cited by 8 publications

(10 citation statements)

References 20 publications

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“…Secondly, the fragments (nitrogen heterocyclic fragments) of pyrido[2,3‐d]pyrimidine 9 and pyrrolo[2,3‐d]pyrimidines 8a‐d were synthesized according to the synthesis method previously mentioned by our research group [19]. Finally, endoperoxide‐type pyrrolo[2,3‐d]pyrimidine derivatives ( Y1 ~ Y8 ) were obtained by condensation of 7a‐c and intermediates 8a‐d .…”

Section: Resultsmentioning

confidence: 99%

“…IR spectra were measured with PerkinElmer Spectrum 3FT‐IR spectrometer. Melting points were recorded on an XT‐4 binocular microscope melting point instrument and were uncorrected [19]. All the synthesized peroxides and are low at risk of explosion with good safety and stability.…”

Section: Methodsmentioning

confidence: 99%

“…Based on the biological relationship between cyclin D and CDK 4/6, we can rationally assume that hybridized molecules combined by the key fragments of palbociclib or ribociclib and an endoperoxide moiety can exert favorable effects on the treatment of breast cancers (Figure 3). We have reported a series of hybrid molecules combined the pivotal structure of artemisinin with the key fragments of palbociclib or ribociclib (Figure 3), among them, 3 and 4 were more potent than ribociclib towards breast T47D cells (an ER + breast cancer cell line) and MDA-MB-436 cells (a triple-negative breast cancer cell line) [19].…”

Section: Introductionmentioning

confidence: 99%

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Design, synthesis, and anti‐breast cancer activity evaluation of endoperoxide‐type pyrido/pyrrolo[2,3‐d]pyrimidine derivatives

Song

Xia

et al. 2023

Journal of Heterocyclic Chem

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Cyclin‐dependent kinase 4 and 6 (CDK 4/6) overactivation in breast cancer cells has given birth to the successful development of CDK 4/6 inhibitors. Based on the intrinsic relationship of CDK 4/6 and cyclin D, we designed and synthesized a series of endoperoxide‐type pyrido/pyrrolo[2,3‐d]pyrimidine derivatives via extracting active fragments from canonical CDK 4/6 inhibitors and endoperoxide‐type natural products such as artemisinin and plakortin. Eleven novel endoperoxide‐type hybrids were synthesized and characterized by mass spectrometry (MS), high resolution mass spectrometry (HRMS), infrared spectroscopy (IR), hydrogen‐1 nuclear magnetic resonance (1H NMR), and carbon‐13 nuclear magnetic resonance (13C NMR) data. Antiproliferative activities and CDK 4/6 inhibitory effects of target compounds were evaluated via T47D, MDA‐MB‐436 breast cancer cell lines, and CDK6/cyclin D3 kinase respectively. The results showed that S1 and Y7 were the most potent compounds against CDK6/cyclin D3 kinase, with Half maximal inhibitory concentration (IC50) values of 0.126 ± 0.022 and 0.109 ± 0.007 μM respectively, they were about a half or third as potent as positive control palbociclib (0.045 μM). The antiproliferative effects of S2 were close to positive controls palbociclib and ribociclib, with Growth inhibitory dose 50% (GI50) values of 8.42 ± 0.93 and 18.74 ± 1.78 μM towards T47D cells and MDA‐MB‐436 cells respectively. Finally, antiproliferative activities against MCF‐10A cells indicated that our newly synthesized compounds were harmless to normal human mammary epithelial cells.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Design, synthesis, and anti‐breast cancer activity evaluation of endoperoxide‐type pyrido/pyrrolo[2,3‐d]pyrimidine derivatives

Song

Xia

et al. 2023

Journal of Heterocyclic Chem

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“…Other naphthenic or heterocyclic acids were also selected to esterify MMB to obtain ZA‐3 ~ ZA‐13. In addition, the functional fragment of the marketed CDK4/6 inhibitor [28] was introduced at the C ‐14 position of MMB to obtain ZB‐1; or introduce simple aromatic amines to obtain ZB‐2 and ZB‐3, and investigate whether the introduction of nitrogen‐containing fragments can enhance the antitumor effect of PTL derivatives (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Study on antitumor activity of parthenolide C‐14 derivatives

Zhou

Zhong

et al. 2023

Journal of Heterocyclic Chem

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In this study, two series of C‐14 derivatives of parthenolide were designed, and synthesized 13 ester derivatives were obtained by oxidation and further esterification of their C‐14 methyl groups. Similarly, the C‐14‐oxidative product suffered from iodination and reacted with amino compounds to afford 3 amine derivatives. Antiproliferative test in vitro exhibited that most of the newly synthesized compounds were more potent than parthenolide toward both human non‐small cell lung cancer A549 cell line and breast cancer MDA‐MB‐231 cell line. Among them, ZA‐5 displayed a significant antiproliferative effect against A549 with an IC50 value of 1.03 μmol L−1 and ZB‐1 had a potency almost equal to that of the positive drug Adriamycin toward MDA‐MB‐231 cells. Finally, a mechanism study showed that ZA‐5 could significantly trigger off apoptosis of A549 cells at the test concentration.

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“…Among synthesized compounds, 165 displayed maximum anticancer activity towards MDA-MB-436 and T-47D with IC 50 values of 10.52 and 3.02 µM. Ribociclib was used as positive control with IC 50 values 24.35 and 4.81 µM, respectively [ 276 ].…”

Section: Current Advances In Nitrogen Containing Heterocycles As Anti...mentioning

confidence: 99%

Nitrogen Containing Heterocycles as Anticancer Agents: A Medicinal Chemistry Perspective

et al. 2023

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Cancer is one of the major healthcare challenges across the globe. Several anticancer drugs are available on the market but they either lack specificity or have poor safety, severe side effects, and suffer from resistance. So, there is a dire need to develop safer and target-specific anticancer drugs. More than 85% of all physiologically active pharmaceuticals are heterocycles or contain at least one heteroatom. Nitrogen heterocycles constituting the most common heterocyclic framework. In this study, we have compiled the FDA approved heterocyclic drugs with nitrogen atoms and their pharmacological properties. Moreover, we have reported nitrogen containing heterocycles, including pyrimidine, quinolone, carbazole, pyridine, imidazole, benzimidazole, triazole, β-lactam, indole, pyrazole, quinazoline, quinoxaline, isatin, pyrrolo-benzodiazepines, and pyrido[2,3-d]pyrimidines, which are used in the treatment of different types of cancer, concurrently covering the biochemical mechanisms of action and cellular targets.

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Design, synthesis, and anti-breast-cancer activity evaluation of pyrrolo(pyrido)[2,3-d]pyrimidine derivatives

Cited by 8 publications

References 20 publications

Design, synthesis, and anti‐breast cancer activity evaluation of endoperoxide‐type pyrido/pyrrolo[2,3‐d]pyrimidine derivatives

Design, synthesis, and anti‐breast cancer activity evaluation of endoperoxide‐type pyrido/pyrrolo[2,3‐d]pyrimidine derivatives

Study on antitumor activity of parthenolide C‐14 derivatives

Nitrogen Containing Heterocycles as Anticancer Agents: A Medicinal Chemistry Perspective

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