Search Results (29)

Cancer is one of the most lethal diseases of this century. Unfortunately, many anticancer agents have harsh side effects or fail to work against cancer any longer due to tolerance. Dihydropyrimidinones are promising structures containing a pyrimidine ring. Targeting Eg5 is their most well-known activity. Inhibition of this enzyme gives them the privilege of strong cytotoxic activity with less side effects. Phenyl ring is a group that can be found in the majority of organic molecules and possesses preferable pharmacokinetic and pharmacodynamic characteristics. This review studies DHPM derivatives that are substituted with a phenyl ring and possess antiproliferative ability by inhibiting Eg5. The compounds are able to inhibit different cancer cell lines, and some are more potent than the standard drug. The biological results are in accordance with the docking studies. Full article

Combining the pharmacological properties of the 1,2,3-triazole and dihydropyrimidinone classes of compounds, two small families of mono- and di(1,2,3-triazole)-dihydropyrimidinone hybrids, A and B, were previously synthesized. The main objective of this work was to investigate the potential anti-Alzheimer effects of these hybrids. The inhibitory activities of cholinesterases (AChE and BuChE), antioxidant activity, and the inhibitory mechanism through in silico (molecular docking) and in solution (STD-NMR) experiments were evaluated. The 1,2,3-triazole-dihydropyrimidinone hybrids (A and B) showed moderate in vitro inhibitory activity on eqBuChE (IC₅₀ values between 1 and 58.4 μM). The best inhibitor was the hybrid B4, featuring two 1,2,3-triazole cores, which exhibited stronger inhibition than galantamine, with an IC₅₀ of 1 ± 0.1 μM for eqBuChE, through a mixed inhibition mechanism. Among the hybrids A, the most promising inhibitor was A1, exhibiting an IC₅₀ of 12 ± 2 µM, similar to that of galantamine. Molecular docking and STD-NMR experiments revealed the key binding interactions of these promising inhibitors with BuChE. Hybrids A and B did not display Artemia salina toxicity below 100 μM. Full article

The relevance of the asymmetric Biginelli reaction (ABR) has been increased in this century, due to the pharmacological application of its products. This review focuses predominantly on articles published in the period from 2015 to 2024 on asymmetric synthetic advances in the formation of dihydropyrimidinones (DHPMs), dihydropyrimidinethiones (DHPMTs), and related compounds. The relevant bibliography on general processes in the Biginelli reaction and some methods of separation of isomers have also been referenced. Full article

In this study, we present the highly efficient and rapid synthesis of substituted dihydropyrimidinone derivatives through an ultrasound-accelerated approach. We utilize copper ferrite (CuFe₂O₄) magnetic nanoparticles as heterogeneous catalysts, employing the well-known Biginelli reaction, under solvent-free conditions. The impact of the solvent, catalyst amount, and catalyst type on the reaction performance is thoroughly investigated. Our method offers several notable advantages, including facile catalyst separation, catalyst reusability for up to three cycles with the minimal loss of activity, a straightforward procedure, mild reaction conditions, and impressive yields, ranging from 79% to 95%, within short reaction times of 20 to 40 min. Furthermore, in the context of fighting COVID-19, we explore the potential of substituted dihydropyrimidinone derivatives as inhibitors of three crucial SARS-CoV-2 proteins. These proteins, glycoproteins, and proteases play pivotal roles in the entry, replication, and spread of the virus. Peptides and antiviral drugs targeting these proteins hold great promise in the development of effective treatments. Through theoretical molecular docking studies, we compare the binding properties of the synthesized dihydropyrimidinone derivatives with the widely used hydroxychloroquine molecule as a reference. Our findings reveal that some of the tested molecules exhibit superior binding characteristics compared to hydroxychloroquine, while others demonstrate comparable results. These results highlight the potential of our synthesized derivatives as effective inhibitors in the fight against SARS-CoV-2. Full article

Halloysite nanotubes can be used for the preparation of solid catalysts. Owing to their natural availability at low-cost as well as to their large and easy-to-functionalize surface, they can be conveniently activated with mineral acids or derivatized with acidic groups. Nevertheless, the use of HNTs as catalysts in complex transformations is still limited. Herein, we report two strategies to utilize HNT-based materials as solid acidic catalysts for the Biginelli reaction. To this aim, two methods for increasing the number of acidic sites on the HNTs were explored: (i) the treatment with piranha solution (Pir-HNTs) and (ii) the functionalization with phenylboronic acid (in particular with benzene-1,4-diboronic acid: the sample is denoted as HNT-BOA). Interestingly, both strategies enhance the performance of the multicomponent reaction. Pir-HNTs and HNT-BOA show an increased reactivity (72% and 89% yield, respectively) in comparison with pristine HNTs (52%). Additionally, Pir-HNTs can be reused up to five times without significant performance loss. Moreover, the method also displays good reaction scope, as demonstrated by the preparation of 12 different 3,4-dihydropyrimidinones in up to 71% yield. Therefore, the described strategies are promising for enhancing the acidity of the HNTs as catalysts for the organic reaction. Full article

Bioactive dihydropyrimidinones (DHPs) were designed and synthesized by a multicomponent Biginelli reaction. The reaction was catalyzed by the polarized surface of nano-zirconium dioxide with partial positive charge of 0.52e at the Zr center and a negative charge of −0.23e at the oxygen center. There was good corroboration between the computed and experimental ZrO₂ cell parameters and bond distances as determined by in silico and in vitro experimental methods. Since DHPs were found to target the peroxisome proliferator-activated receptor (PPAR)-γ, we tested these ligands toward MCF-7 cell toxicity, which revealed that the compounds 4d [ethyl-4-(4′-fluoro-[1,1′-biphenyl]-4-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate] and 4e [ethyl-4-(3′-methoxy-[1,1′-biphenyl]-4-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate] inhibited proliferation with IC₅₀ values of 11.8 and 15.8 μM, respectively. Further, our bioinformatic analysis found that the active molecule 4d, fit into the enzyme’s catalytic site, almost in the same position as rosiglitazone, which was buried deep inside the cavity. In conclusion, we herein report novel DHPs which could be better structures to help explore a new class of synthetic PPAR-γ ligands. Full article

Designed Chalcone-Dihydropyrimidinone hybrid compounds were synthesized expeditiously. The hybridization was performed through the Copper-catalyzed Alkyne-Azide Cycloaddition (CuAAC) from the propargyloxy chalcones and azido-dihydropyrimidinones. The hybrid products were prepared in five steps with a 30–48% overall yield. Most of the compounds showed selective cytotoxicity and lower IC₅₀ values (<10 µM) against MCF-7 (breast adenocarcinoma) cancer. Cytotoxicity was also observed against OVCAR-3 (ovary, adenocarcinoma), NCI/ADR-RES (ovary, multidrug-resistant adenocarcinoma), and U-251 (brain, glioblastoma) cell lines. The potency of the most active hybrids 9d, 9g, and 9h was greater than the individual parental compounds, suggesting the effectiveness of molecular hybridization on the cytotoxicity. Compounds 9d, 9g, and especially 9h showed high selectivity for breast cancer cells (MCF-7) regarding human keratinocytes (HaCaT). Molecular docking calculations for the 9d, 9g, and 9h hybrids in the active site of estrogen supported the hypothesis that the compounds act as ER-α antagonists, disrupting the cell proliferation process of MCF-7, corroborating the potency and selectivity observed for this tumoral cell line. Full article

The interest in 3,4-dihydropyrimidine-2(1H)-(thio)ones is increasing every day, mainly due to their paramount biological relevance. The Biginelli reaction is the classical approach to reaching these scaffolds, although the product diversity suffers from some limitations. In order to overcome these restrictions, two main approaches have been devised. The first one involves the modification of the conventional components of the Biginelli reaction and the second one refers to the postmodification of the Biginelli products. Both strategies have been extensively revised in this manuscript. Regarding the first one, initially, the modification of one of the components was covered. Although examples of modifications of the three of them were described, by far the modification of the keto ester counterpart was the most popular approach, and a wide variety of different enolizable carbonylic compounds were used; moreover, changes in two or the three components were also described, broadening the substitution of the final dihydropyrimidines. Together with these modifications, the use of Biginelli adducts as a starting point for further modification was also a very useful strategy to decorate the final heterocyclic structure. Full article

We have efficiently synthesized mono as well as bis and spiro cyclic products of 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) by refluxing a reaction mixture of the three components in deep eutectic solvent (DES) to generating “libraries from libraries”. Synthesized Spiro fused heterotricyclic compounds containing urea moiety are potent against bacteria. Overall, in the antibacterial study, from the synthesized compounds, some of the 3,4–dihydropyrimidin-2-(1H)-one compounds were found to possess anti-bacterial efficacy. Full article

Solvothermal synthesis of multiple dihydropyrimidinones at a time has been developed in inexpensive and green bio-based solvent lactic acid without any additional catalysts or additives. By this method, thirty new dihydropyrimidinone derivatives were synthesized in two batches and characterized. All of the compounds were screened by Eg5 motor protein ATPase assay, and the positive compounds were tested against the Caco-2 cell line, HeLa cell line, L929 cell line and T24 cell line in vitro. Among them, compound C9 exhibited the best inhibitory activity against motor protein ATPase with an IC₅₀ value of 30.25 μM and significant cytotoxic activity in the micromolar range against the cells above. The Lineweaver–Burk plot revealed that compound C9 was a mixed-type Eg5 inhibitor. A molecular modeling study using the Discovery Studio program was performed, where compound C9 exhibited good binding interaction with Eg5 motor protein ATPase, and this was consistent with the attained experimental results. Full article

A novel biochar-based graphitic carbon nitride was prepared through calcination of Zinnia grandiflora petals and urea. To provide acidic and ionic-liquid functionalities on the prepared carbon, the resultant biochar-based graphitic carbon nitride was vinyl functionalized and polymerized with 2-acrylamido-2-methyl-1-propanesulfonic acid, acrylic acid and the as-prepared 1-vinyl-3-butylimidazolium chloride. The final catalytic system that benefits from both acidic (–COOH and –SO₃H) and ionic-liquid functionalities was applied as a versatile, metal-free catalyst for promoting some model acid catalyzed reactions such as Knoevenagel condensation and Biginelli reaction in aqueous media under a very mild reaction condition. The results confirmed high activity of the catalyst. Broad substrate scope and recyclability and stability of the catalyst were other merits of the developed protocols. Comparative experiments also indicated that both acidic and ionic-liquid functionalities on the catalyst participated in the catalysis. Full article

A library of dihydropyrimidinones was synthesized via a “one-pot” three component Biginelli reaction using different aldehydes in combination with β-dicarbonyl compounds and urea. Selected 2-thiooxo and 2-imino analogs were also obtained with the Biginelli reaction from thiourea and guanidine hydrochloride, respectively. The products were screened in vitro for their β-secretase inhibitory activity. The majority of the compounds resulted to be active, with IC₅₀ in the range 100 nM–50 μM. Full article

The Biginelli reaction is an acid-catalyzed, three-component reaction between an aldehyde, a hydrogen methylene active compound, and urea (or its analogue) and constitutes a rapid and easy synthesis of highly functionalized heterocycles. Synthesis of ethyl 6-methyl-2-oxo-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,2,3,4-tetrahydropyrimidine-5-carboxylate, identified by our laboratory code LaSOM^® 293, was achieved using the Biginelli reaction as the key step, followed by the Huisgen 1,3-dipolar cycloaddition in a convergent four-step route. The product LaSOM^® 293 was obtained with a yield of 84%. Full article

The anchorage of a supported copper Schiff base complex on SBA-15 materials provides highly efficient heterogeneous catalysts towards the solvent-free synthesis of dihydropyrimidinones derivatives via the Biginelli condensation reaction. The novel nanocatalysts exhibited a highly ordered mesostructure with a surface area of 346 m²g⁻¹ and an average pore diameter of 8.6 nm. Additionally, the supported copper nanocatalysts were reused at least ten times, remaining almost unchanged from the initial activity. Both the mesoporous scaffold and the tridentate Schiff base ligand contributed to the stabilization of copper species. Full article

The Biginelli reaction is a highly versatile reaction that leads to dihydropyrimidinones/thiones. This scaffold is reported as being a privileged structure due to its ability to interact with biological targets. Synthesis of ethyl 4-(2-fluorophenyl)-6-methyl-2-thioxo-1-(p-tolyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate was achieved through the Biginelli reaction using a functionalized thiourea. In silico studies demonstrated that the compound title showed good potential for interacting with ecto-5’-nucleotidase, which has been considered as a target in designs for anti-cancer drugs. Full article