Recent Advances in the Chemical Synthesis and Evaluation of Anticancer Nucleoside Analogues

Guinan, Mieke; Benckendorff, Caecilie M M; Smith, Mark E.; Miller, Gavin J.

doi:10.3390/molecules25092050

Cited by 89 publications

(60 citation statements)

References 82 publications

(98 reference statements)

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“…In this research, our strategy was directed towards developing new fused uracil derivatives of potential anticancer activity [ 33 , 34 ]. The desired starting materials, including 6-amino-1-benzyluracil 1a [ 35 ] and 5,6-diamino-1-(2-chlorobenzyl)uracil 4 [ 36 ] were synthesized according to the literature by conventional methods.…”

Section: Resultsmentioning

confidence: 99%

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

El‐Kalyoubi

Agili

2020

Molecules

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Ethyl 5-arylpyridopyrimidine-6-carboxylates 3a–d were prepared as a one pot three component reaction via the condensation of different aromatic aldehydes and ethyl acetoacetate with 6-amino-1-benzyluracil 1a 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 3e; a facile, operationally, simple and efficient one-pot synthesis of 8-arylxanthines 6a–f is reported by refluxing 5,6-diaminouracil 4 with aromatic aldehydes in DMF. Moreover, 6-aryllumazines 7a–d was obtained via the reaction of 5,6-diaminouracil with the appropriate aromatic aldehydes in triethyl orthoformate under reflux condition. The synthesized compounds were characterized by spectral (1H-NMR, 13C-NMR, IR and mass spectra) and elemental analyses. The newly synthesized compounds were screened for their anticancer activity against lung cancer A549 cell line. Furthermore, a molecular-docking study was employed to determine the possible mode of action of the synthesized compounds against a group of proteins highly implicated in cancer progression, especially lung cancer. Docking results showed that compounds 3b, 6c, 6d, 6e, 7c and 7d were the best potential docked compounds against most of the tested proteins, especially CDK2, Jak2, and DHFR proteins. These results are in agreement with cytotoxicity results, which shed a light on the promising activity of these novel six heterocyclic derivatives for further investigation as potential chemotherapeutics.

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Section: Resultsmentioning

confidence: 99%

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

El‐Kalyoubi

Agili

2020

Molecules

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“…In addition, it has been shown that warm/hot-natured herbs contain more nucleotides and their derivatives (Figures 4 and 5). Immunity, inflammation, and cancer can all be regulated by extracellular nucleosides [33][34][35]. Furthermore, based on the functional activities of the metabolites, Liang et al searched the protein targets of active compounds in the PubChem database and found that immune regulation was more related to hot-natured herbs and that cold-natured herbs possess the tendency to impact cell growth and proliferation [36].…”

Section: Discussionmentioning

confidence: 99%

Quantitative and Molecular Similarity Analyses of the Metabolites of Cold- and Hot-Natured Chinese Herbs

Guo

Wang²,

Iino

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Based on the theory of traditional Chinese medicine, Chinese herbs possess four different medicinal properties: hot, warm, cold, and cool. These serve as a reference guide for these herbal medicines. However, the molecular mechanisms supporting their relevance remain unclear. Methods. We performed metabolomics based on capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS) and multivariate data analysis for the structural identification of compounds of cold- and hot-natured Chinese herbs. Results. To this end, 30 selected herbs were analyzed and a total of 416 metabolites were identified via CE-TOF/MS, of which 193 compounds were detected in most herbs. The observed profiles offered the potential to understand the mechanism of association between the compounds and nature of the Chinese herbs. Comparison of the similarity in terms of chemical and molecular structures and content revealed that hot-natured herbs contained more nucleotides. In contrast, principal component analysis revealed the presence of more amino acid compounds in cold-natured herbs. Conclusion. Comparing the structural similarities between the samples using the Tanimoto coefficient revealed that a general non-specific structure was observed between cold- and hot-natured herbs; however, the distribution of the molecular groups seemed to contribute more toward the energy properties.

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“…The carbocyclic analogues of nucleosides attenuate the synthesis of DNA by acting as chain terminators after incorporating to the growing DNA chain. The prevention of the DNA chain elongation by carbocyclic analogues of nucleosides offers antineoplastic properties [35] …”

Section: Anticancer Properties Of Indane and Its Analoguesmentioning

confidence: 99%

Medicinal Chemistry of Indane and Its Analogues: A Mini Review

Prasher

Sharma

2021

ChemistrySelect

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‘Indane′ and its analogues indene, 1‐indenone, and 1,3‐indandione present an attractive biological profile for the rational development of therapeutic molecules. The indane/ indene moieties contain aromatic benzene ring fused with an aliphatic cyclopentane/ cyclopentene ring, which provides a rigid bicyclic ring‐framework enriched with diverse chemical properties. The multifarious possibilities for varying the substituent pattern on these fused ring systems enable the extensive appraisal of structure‐activity relationship analysis of rationally designed therapeutic molecules deliberated at their molecular targets. Indane analogues serve as useful scaffolds for the development of efficacious pharmaceuticals and commercial drugs, including Indinavir, Sulindac, and donepezil; whereas the pharmacophores based on indane moiety such as Aminoindanes and Indanedione contribute towards the development of neuroleptics and neuroprotective molecules. Similarly, the Indane‐carboxamide derivatives present a robust candidature as CGRP receptor antagonists, while substituted Indane and its analogue Indene present a privileged profile for the development of anticancer therapeutics by targeting the multifaceted oncologic pathways. Besides, the indane natural product scaffolds serve as perspective drug candidates with marked therapeutic properties. The present review summarizes the medicinal chemistry aspects of indane nucleus and its analogues as anticancer, anti‐inflammatory, and neuroprotective agents for the coherent development of impending therapeutics.

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Recent Advances in the Chemical Synthesis and Evaluation of Anticancer Nucleoside Analogues

Cited by 89 publications

References 82 publications

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

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

Quantitative and Molecular Similarity Analyses of the Metabolites of Cold- and Hot-Natured Chinese Herbs

Medicinal Chemistry of Indane and Its Analogues: A Mini Review

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