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

Mahapatra, Aastha; Prasad, Tanya; Sharma, Tripti

doi:10.1186/s43094-021-00274-8

Cited by 67 publications

(43 citation statements)

References 143 publications

(110 reference statements)

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“…Isosteric replacement of -NH with (-S-) has literature precedence in improving antiproliferative and microtubule depolymerizing activities [ 27 ]. Moreover, pharmacological applications of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3- d ]pyrimidines have been extensively illustrated in various reports in the literature [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. In addition, the lead tricyclic compounds and the proposed target compounds incorporate a p-methoxyphenyl substitution akin to colchicine and CA-4 ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as Microtubule Targeting Agents

et al. 2022

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A series of eleven 4-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines were designed and synthesized and their biological activities were evaluated. Synthesis involved the Gewald reaction to synthesize ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ring, and SNAr reactions. Compound 4 was 1.6- and ~7-fold more potent than the lead compound 1 in cell proliferation and microtubule depolymerization assays, respectively. Compounds 4, 5 and 7 showed the most potent antiproliferative effects (IC50 values < 40 nM), while compounds 6, 8, 10, 12 and 13 had lower antiproliferative potencies (IC50 values of 53–125 nM). Additionally, compounds 4–8, 10 and 12–13 circumvented Pgp and βIII-tubulin mediated drug resistance, mechanisms that diminish the clinical efficacy of paclitaxel (PTX). In the NCI-60 cell line panel, compound 4 exhibited an average GI50 of ~10 nM in the 40 most sensitive cell lines. Compound 4 demonstrated statistically significant antitumor effects in a murine MDA-MB-435 xenograft model.

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Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as Microtubule Targeting Agents

et al. 2022

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“…Schiff bases are prepared by condensation of an amine and carbonyl compounds and these are significant types of ligands that coordinate to metal ions through azomethine nitrogen. 9 It is regarded as a nitrogen analogue of an aldehyde or ketone where the imine group substitutes the C=O group. Therefore, it is also known as imine or azomethine.…”

Section: Schiff Base Scaffoldsmentioning

confidence: 99%

In-silico approach: docking study of novel Schiff base congeners of pyrimidine nucleus

Karati¹

2022

JAPLR

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Pyrimidine nucleus has a wide spectrum use in medicinal chemistry. Based on structure activity relationship of pyrimidine nucleus we are going to synthesize 4-amino-2-methyl-6-phenylpyrimidine-5-carbonitrile derivatives. In this structure one primary amine group is free at 4th position. Schiff base has excellent antibacterial, antifungal, antiviral activities due to presence of azomethine (CH=N) group. Schiff base compounds have extensive applications in various fields such as analytical, inorganic, organic, and biological fields. They have excellent pharmacology application prospects in the modern era and are widely used in the pharmaceutical industry. In the present work in silico docking studies of five Schiff base compounds were carried out against Staphylococcus aureus.

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“…Pyrimidine and its substantial groups of novel derivatives are members of the heterocyclic aromatic family. The pyrimidine molecular structure is primarily composed of a core heteroaromatic ring that included two nitrogen atoms [ 1 , 2 , 3 ]. Pyrimidines have important pharmacological properties because they are an integral element of DNA and RNA.…”

Section: Introductionmentioning

confidence: 99%

DFT, ADMET and Molecular Docking Investigations for the Antimicrobial Activity of 6,6′-Diamino-1,1′,3,3′-tetramethyl-5,5′-(4-chlorobenzylidene)bis[pyrimidine-2,4(1H,3H)-dione]

et al. 2022

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Heterocyclic compounds, including pyrimidine derivatives, exhibit a broad variety of biological and pharmacological activities. In this paper, a previously synthesized novel pyrimidine molecule is proposed, and its pharmaceutical properties are investigated. Computational techniques such as the density functional theory, ADMET evaluation, and molecular docking were applied to elucidate the chemical nature, drug likeness and antibacterial function of molecule. The viewpoint of quantum chemical computations revealed that the molecule was relatively stable and has a high electrophilic nature. The contour maps of HOMO-LUMO and molecular electrostatic potential were analyzed to illustrate the charge density distributions that could be associated with the biological activity. Natural bond orbital (NBO) analysis revealed details about the interaction between donor and acceptor within the bond. Drug likeness and ADMET analysis showed that the molecule possesses the agents of safety and the effective combination therapy as pharmaceutical drug. The antimicrobial activity was investigated using molecular docking. The investigated molecule demonstrated a high affinity for binding within the active sites of antibacterial and antimalarial proteins. The high affinity of the antibacterial protein was proved by its low binding energy (−7.97 kcal/mol) and a low inhibition constant value (1.43 µM). The formation of four conventional hydrogen bonds in ligand–protein interactions confirmed the high stability of the resulting complexes. When compared to known standard drugs, the studied molecule displayed a remarkable antimalarial activity, as indicated by higher binding affinity (B.E. −5.86 kcal/mol & Ki = 50.23 M). The pre-selected molecule could be presented as a promising drug candidate for the development of novel antimicrobial agents.

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

Cited by 67 publications

References 143 publications

Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as Microtubule Targeting Agents

Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as Microtubule Targeting Agents

In-silico approach: docking study of novel Schiff base congeners of pyrimidine nucleus

DFT, ADMET and Molecular Docking Investigations for the Antimicrobial Activity of 6,6′-Diamino-1,1′,3,3′-tetramethyl-5,5′-(4-chlorobenzylidene)bis[pyrimidine-2,4(1H,3H)-dione]

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