Design, synthesis, cytotoxicity, and molecular modeling study of 2,4,6-trisubstituted pyrimidines with anthranilate ester moiety

Черемных, Кирилл П.; Savelyev, Victor A.; Покровский, М. А.; Baev, Dmitry S.; Толстикова, Т. Г.; Покровский, А. Г.; Шульц, Э. Э.

doi:10.1007/s00044-019-02314-8

Cited by 19 publications

(13 citation statements)

References 57 publications

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“…The SAR studies reveal that the major activity is due to the (E)-styryl moiety at C-6 position, methyl group at R 2 position, and the presence of methylanthranilate moiety with an EDG at C-4 lead to better activity (Fig. 4) [14].…”

Section: 4 6-trisubstituted Pyrimidinesmentioning

confidence: 99%

Pyrimidine: a review on anticancer activity with key emphasis on SAR

2021

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Background Cancer is a global health challenge, it impacts the quality of life and its treatment is associated with several side effects. Resistance of the cancer cells to the existing drugs has led to search for novel anticancer agents. Pyrimidine, a privileged scaffold, is part of living organisms and plays vital role in various biological procedures as well as in cancer pathogenesis. Due to resemblance in structure with the nucleotide base pair of DNA and RNA, it is recognized as valuable compound in the treatment of cancer. Main text Many novel pyrimidine derivatives have been designed and developed for their anticancer activity in the last few years. The present review aims to focus on the structure activity relationship (SAR) of pyrimidine derivatives as anticancer agent from the last decade. Conclusion This review intends to assist in the development of more potent and efficacious anticancer drugs with pyrimidine scaffold. Graphical abstract

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Section: 4 6-trisubstituted Pyrimidinesmentioning

confidence: 99%

Pyrimidine: a review on anticancer activity with key emphasis on SAR

2021

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“…As the palladium catalytic system in the three-component reaction of 5 -iodolappaconitine 17 with phenyl acetylene 18, we used the practical Beller's ligand [di(1-adamantyl)benzyl phosphonium bromide] Ad 2 PBn•HBr and PdCl 2 as the source of palladium. This copper-free system was previously employed in Sonogashira coupling [48,49]. The reaction in MeCN proceeds for 2 h (65 • C, TLC-control) with the formation of 5 -(1-oxo-3-phenylprop-2-in-1-yl)lappaconitine 19 with the isolated yield 78% (Scheme 3).…”

Section: Chemical Synthesismentioning

confidence: 99%

“…as the source of palladium. This copper-free system was previously employed in Sonogashira coupling [48,49]. The reaction in MeCN proceeds for 2 h (65 °C, TLC-control) with the formation of 5′-(1-oxo-3-phenylprop-2-in-1-yl)lappaconitine 19 with the isolated yield 78% (Scheme 3) Next, we questioned whether the power and efficiency of this designed reaction sequence could be further improved, by combining in situ formation of the alkynyl ketone 19, and its cyclocondensation reactions with amidines; thus, make the catalytic process more economic and attractive.…”

Section: Chemical Synthesismentioning

confidence: 99%

Hybrides of Alkaloid Lappaconitine with Pyrimidine Motif on the Anthranilic Acid Moiety: Design, Synthesis, and Investigation of Antinociceptive Potency

et al. 2020

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Convenient and efficient routes to construct hybrid molecules containing diterpene alkaloid lappaconitine and pyrimidine fragments are reported. One route takes place via first converting of lappaconitine to 1-ethynyl-lappaconitine, followed by the Sonogashira cross-coupling-cyclocondensation sequences. The other involves the palladium-catalyzed carbonylative Sonogashira reaction of 5′-iodolappaconitine with aryl acetylene and Mo (CO)6 as the CO source in acetonitrile and subsequent cyclocondensation reaction of the generated alkynone with amidines. The reaction proceeded cleanly in the presence of the PdCl2-(1-Ad)2PBn∙HBr catalytic system. The protocol provides mild reaction conditions, high yields, and high atom and step-economy. Pharmacological screening of lappaconitine-pyrimidine hybrids for antinociceptive activity in vivo revealed that these compounds possessed high activity in experimental pain models, which was dependent on the nature of the substituent in the 2 and 6 positions of the pyrimidine nucleus. Docking studies were undertaken to gain insight into the possible binding mode of these compounds with the voltage-gated sodium channel 1.7. The moderate toxicity of the leading compound 12 (50% lethal dose (LD50) value was more than 600 mg/kg in vivo) and cytotoxicity to cancer cell lines in vitro encouraged the further design of therapeutically relevant analogues based on this novel type of lappaconitine–pyrimidine hybrids.

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“…Pyrimidines are considered one of the most heterocyclic derivatives that are characterized by broad-spectrum activity. It is recognized as antibacterial, antifungal, anti-inflammatory, antiproliferative, antitumor, antiviral, antileishmanial, anticonvulsant, antimalarial activity, anti-tuberculosis, analgesic activity and acts as an enzyme inhibitor, anti-Parkinson drug, and antioxidant compounds [17][18][19][20][21]. Moreover, pyrimidine derivatives exhibit high antiviral activity against various DNA/RNA viruses such as varicella-zoster virus (VZV), human cytomegalovirus (HCMV), human immunodeficiency virus (HIV), and polioviruses [22].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of the novel pyrimidine’s derivatives, as a promising tool for antimicrobial agent and in-vitro cytotoxicity

et al. 2021

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Herein, the biological activities including antibacterial, antifungal, and in-vitro cytotoxicity for some novel substituted pyrazolo [3,4-d]pyrimidinone, benzylidene dihydropyrimidine, pyrano [2,3-d]pyrimidine, hexahydropyrimido[4, 5-d]pyrimidinone, tetrahydropyrido[2,3-d]pyrimidine-6-carbonitrile, and pyrido[2, 3-d:6,5-d'] dipyrimidinone derivatives were investigated. The synthesized novel compounds were achieved through the incorporation of the active moieties such as halo compound, pyrazolo, pyrano, pyrimido, pyrido-derivatives with active methylene group in thiobarbituric acid derivatives at C-5. Structures of all synthesized compounds were characterized by spectral techniques including IR, 1 H-NMR, MS, and 13 C-NMR. All synthesized compounds were screened for their antibacterial and antifungal activity, while the most promising compounds were selected to investigate their in-vitro cytotoxic efficacy against normal Vero cells and cancerous Caco-2 cells. Data showed that the biological activities were concentration-dependent. All novel pyrimidine derivatives exhibited broad-spectrum antimicrobial activity with a varied zone of inhibition ranging between 11.3 ± 0.6 and 25.3 ± 0.6 mm. The MIC values are different according to a pathogenic organism (ranging between 3.91 and 500 µg mL −1 ), whereas the MBC/ MFC were 2 × to 4 × MIC value. Data of in-vitro cytotoxicity confirm the efficiency of selected novel pyrimidine derivatives to target Caco-2 cancerous cells at low concentrations more Vero normal cells. Four selected compounds 4, 7b, 10, and

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Design, synthesis, cytotoxicity, and molecular modeling study of 2,4,6-trisubstituted pyrimidines with anthranilate ester moiety

Cited by 19 publications

References 57 publications

Pyrimidine: a review on anticancer activity with key emphasis on SAR

Pyrimidine: a review on anticancer activity with key emphasis on SAR

Hybrides of Alkaloid Lappaconitine with Pyrimidine Motif on the Anthranilic Acid Moiety: Design, Synthesis, and Investigation of Antinociceptive Potency

Synthesis and characterization of the novel pyrimidine’s derivatives, as a promising tool for antimicrobial agent and in-vitro cytotoxicity

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