Medicinal attributes of pyridine scaffold as anticancer targeting agents

Mohamed, Esraa A.; Ismail, Nasser S. M.; Hagras, Mohamed; Refaat, Hanan M.

doi:10.1186/s43094-020-00165-4

Cited by 50 publications

(16 citation statements)

References 53 publications

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“…Pyridines can target a wide range of cellular components, includ and PIM-1 kinases (both enzymes involved during cancer developm interesting targets for inhibition during treatment [32]. In parallel w geranylpyrrol A ( 24 Nocarimidazoles C and D (35,36) were isolated from Kocuria sp.…”

Section: Pyridinesmentioning

confidence: 99%

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Novel Alkaloids from Marine Actinobacteria: Discovery and Characterization

et al. 2021

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The marine environment is an excellent resource for natural products with therapeutic potential. Its microbial inhabitants, often associated with other marine organisms, are specialized in the synthesis of bioactive secondary metabolites. Similar to their terrestrial counterparts, marine Actinobacteria are a prevalent source of these natural products. Here, we discuss 77 newly discovered alkaloids produced by such marine Actinobacteria between 2017 and mid-2021, as well as the strategies employed in their elucidation. While 12 different classes of alkaloids were unraveled, indoles, diketopiperazines, glutarimides, indolizidines, and pyrroles were most dominant. Discoveries were mainly based on experimental approaches where microbial extracts were analyzed in relation to novel compounds. Although such experimental procedures have proven useful in the past, the methodologies need adaptations to limit the chance of compound rediscovery. On the other hand, genome mining provides a different angle for natural product discovery. While the technology is still relatively young compared to experimental screening, significant improvement has been made in recent years. Together with synthetic biology tools, both genome mining and extract screening provide excellent opportunities for continued drug discovery from marine Actinobacteria.

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Section: Pyridinesmentioning

confidence: 99%

“…Pyridines can target a wide range of cellular components, including topoisomerases and PIM-1 kinases (both enzymes involved during cancer development), making them interesting targets for inhibition during treatment [32]. In parallel with the discovery of geranylpyrrol A ( 24 tected.…”

Section: Pyridinesmentioning

confidence: 99%

Novel Alkaloids from Marine Actinobacteria: Discovery and Characterization

et al. 2021

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“…It can be found in clinically approved drugs such as dasatinib, dabrafenib, alpelisib, or ixabepilone [ 6 , 7 ]. The pyridine ring can be found in the structures of several approved targeted anticancer drugs, such as crizotinib, imatinib, neratinib, regorafenib, sorafenib, and vismodegib [ 8 , 9 ]. The quinoline ring allows structure optimization through established synthetic pathways and several compounds based on its structure interact with various oncological targets, like tyrosine kinases, proteasome, tubulin or DNA [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Quantitative and Qualitative Analysis of the Anti-Proliferative Potential of the Pyrazole Scaffold in the Design of Anticancer Agents

Nițulescu

2022

Molecules

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The current work presents an objective overview of the impact of one important heterocyclic structure, the pyrazole ring, in the development of anti-proliferative drugs. A set of 1551 pyrazole derivatives were extracted from the National Cancer Institute (NCI) database, together with their growth inhibition effects (GI%) on the NCI’s panel of 60 cancer cell lines. The structures of these derivatives were analyzed based on the compounds’ averages of GI% values across NCI-60 cell lines and the averages of the values for the outlier cells. The distribution and the architecture of the Bemis–Murcko skeletons were analyzed, highlighting the impact of certain scaffold structures on the anti-proliferative effect’s potency and selectivity. The drug-likeness, chemical reactivity and promiscuity risks of the compounds were predicted using AMDETlab. The pyrazole ring proved to be a versatile scaffold for the design of anticancer drugs if properly substituted and if connected with other cyclic structures. The 1,3-diphenyl-pyrazole emerged as a useful scaffold for potent and targeted anticancer candidates.

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“…Pyridine scaffold is gaining increased attention in modern pharmaceuticals with pyridine-containing compounds possessing multiple biological activities such as antimalarial [7], antiviral [8], anticholinesterase [9], antidiabetic [10] and antimicrobial activities [11]. Most interestingly, pyridine derivatives have been reported to exert potent cytotoxic effects against a variety of cancer cell lines, such as leukemia, colon, and ovarian cancer cell lines [9,12,13]. Byth et al [14] synthesized imidazo [1,2-a] pyridine derivatives as plausible CDK2 inhibitors and investigated their activities against breast cancer cell line (MCF-7).…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and cytotoxic evaluation of 2-amino-4- aryl-6-substituted pyridine-3,5-dicarbonitrile derivatives

Lila¹,

Abdallah²,

Khafagy³

et al. 2021

Trop. J. Pharm Res

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Purpose: To synthesize novel pyridine derivatives and evaluate their efficiency as potent inhibitors of cyclin dependent kinase 2 (CDK2) enzyme for cancer therapy.Methods: Pyridine scaffold were synthesized using one-pot multicomponent condensation reaction of arylidine with different primary amines. The cytotoxic potential of the new compounds was assessed using various cell lines. Furthermore, molecular docking studies based on the crystal structure of CDK2 was carried out to determine the possible binding modes that influence the anticancer activities.Results: The results indicate that one-pot multicomponent reaction generated a series of functionalized pyridines with good yield. In vitro cytotoxicity study revealed superior cytotoxicity of the designed compounds against prostate and cervical cancer cell lines compared to 5-fluorouracil (standard anticancer compound) with half-maximal inhibitory concentration (IC50) values of 0.1 – 0.85 and 1.2 –74.1 μM, respectively. Finally, molecular modeling simulation of the newly synthesized compounds showed that they fit well and are stabilized into CDK2 active site via hydrogen bonding and hydrophobic interactions.Conclusion: The results indicate that the newly synthesized pyridine can exert potent anticancer activity presumably via inhibition of CDK2. However, this will need to be confirmed in in vivo studies.

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Medicinal attributes of pyridine scaffold as anticancer targeting agents

Cited by 50 publications

References 53 publications

Novel Alkaloids from Marine Actinobacteria: Discovery and Characterization

Novel Alkaloids from Marine Actinobacteria: Discovery and Characterization

Quantitative and Qualitative Analysis of the Anti-Proliferative Potential of the Pyrazole Scaffold in the Design of Anticancer Agents

Design, synthesis and cytotoxic evaluation of 2-amino-4- aryl-6-substituted pyridine-3,5-dicarbonitrile derivatives

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