Synthesis and in vitro cytotoxicity evaluation of some fluorinated hexahydropyrimidine derivatives

Agbaje, Oluropo C.; Fadeyi, Olugbeminiyi O.; Fadeyi, Saudat; Myles, Lewis E.; Okoro, Cosmas O.

doi:10.1016/j.bmcl.2010.12.022

Cited by 90 publications

(49 citation statements)

References 26 publications

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“…3,4‐dihydropyrimidine‐2(1 H )‐thiones/ones (Figure ) are very important scaffolds in the synthesis of variety of heterocyclic compounds and have diverse range of biological activities Considering their importance in the synthesis of various heterocycles, a series of fused thiazolo[3, 2‐ a ]pyrimidine derivatives have been synthesized to explore their antileishmanial potential.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Biological Evaluation, Molecular Docking and DFT Study of Potent Antileishmanial Agents Based on the Thiazolo[3, 2‐a]pyrimidine Chemical Scaffold

et al. 2018

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A series of 20 compounds having thiazolo[3, 2‐a]pyrimidine chemical scaffold were synthesized and evaluated for their antileishmanial activity against promastigotes of Leishmania donovani. Amongst all, two compounds showed promising antileishmanial activity in comparison to other compounds. Inhibitory concentration 50% (IC50) was calculated as 42.1 μM and 25.1 μM with selectivity index of 8.3 and 6.05, respectively against Miltefosine (reference drug) 37.78 μM with selectivity index of 2.05. To confirm the target of the these molecules, we modelled Leishmania donovani Ca2+ ion channel (LdCC) protein and performed the docking analysis of the best antileishmanial activity exhibiting inhibitors. The free energy of binding was observed as −10.2 and −9.6 kcal mol−1 in comparison to reference drug −6.2 kcal mol−1. It also makes several hydrogen bonds with our conserved residue Ser1655, Tyr1598 and Asn927. Furthermore, several hydrophobic contacts were also observed within the pocket. Finally, computational work employing density functional theory (DFT) was also carried out to investigate the electronic properties of the synthesized compounds. The in vitro and in silico activities conclusively revealed that our lead compounds may be used as a novel therapeutics against leishmaniasis.

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Section: Resultsmentioning

confidence: 99%

Synthesis, Biological Evaluation, Molecular Docking and DFT Study of Potent Antileishmanial Agents Based on the Thiazolo[3, 2‐a]pyrimidine Chemical Scaffold

et al. 2018

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“…Compound 130 was found to be most potent molecule with IC 50 ¼ 8.1 mM. The anticancer studies showed that compounds 128, 129, 130 and 131 represent novel leads for further development [64]. The structures of potent molecules are shown in Fig.…”

Section: Colon Cancermentioning

confidence: 98%

Recent synthetic and medicinal perspectives of dihydropyrimidinones: A review

Kaur

Chaudhary

Kumar

et al. 2017

European Journal of Medicinal Chemistry

249

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Dihydropyrimidines are the most important heterocyclic ring systems which play an important role in the synthesis of DNA and RNA. Synthetically they were synthesized using Multi-component reactions like Biginelli reaction and Hantzschdihydropyridine. In the past decades, such Biginelli type dihydropyrimidones have received a considerable amount of attention due to the interesting pharmacological properties associated with this heterocyclic scaffold. In this review, we highlight recent developments in this area, with a focus on the DHPMs, recently developed as anti-inflammatory, anti-HIV, anti-tubercular, antifungal anticancer, antibacterial, antifilarial, antihyperglycemic, antihypertensive, analgesic, anti-convulsant, antioxidant, anti-TRPA1, anti-SARS, and anti-cancer activity and α binding affinity.

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“…According to Kappe and coworkers, DHPMs result from the easy dehydration of their precursors hexahydropyrimidine‐2‐ones (HHPMs), itself derived from the intramolecular cyclization of the initially formed Mannich adducts. In spite of the hundred and twenty years elapsed, and the interesting biological profile unveiled for some specific racemic HHPM derivatives, we are not aware of a general synthetic method to enantiopure HHPMs . In fact, none of the reported Biginelli‐type enantioselective protocols towards DHPMs allows for a direct access to HHPMs, as these compounds, having a β‐hydroxy ester unit, easily dehydrate in acidic media to yield DHPMs, but with some exceptions…”

Section: Figurementioning

confidence: 99%

Towards Enzyme‐like, Sustainable Catalysis: Switchable, Highly Efficient Asymmetric Synthesis of Enantiopure Biginelli Dihydropyrimidinones or Hexahydropyrimidinones

Lillo

Saá

2016

Chemistry A European J

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Organocatalysts displaying a network of cooperative hydrogen bonds (NCHB) have been employed in an enzyme-like manner for a direct, switchable synthesis of enantiopure hexahydropyrimidinones (HHPMs) or dihydropyrimidinones (DHPMs), which starts at a common, easily accessible α-ureidosulfone stage. The NCHB organocatalyst exploits all its potential as a pure hydrogen-bond biomimetic catalyst even in the presence of organic bases. This one-pot, diastereo- and enantioselective synthetic procedure has been proven to be robust, scalable, highly efficient, and environmentally benign. A straightforward and truly practical entry to enantiopure HHPMs is reported for the first time.

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Synthesis and in vitro cytotoxicity evaluation of some fluorinated hexahydropyrimidine derivatives

Cited by 90 publications

References 26 publications

Synthesis, Biological Evaluation, Molecular Docking and DFT Study of Potent Antileishmanial Agents Based on the Thiazolo[3, 2‐a]pyrimidine Chemical Scaffold

Synthesis, Biological Evaluation, Molecular Docking and DFT Study of Potent Antileishmanial Agents Based on the Thiazolo[3, 2‐a]pyrimidine Chemical Scaffold

Recent synthetic and medicinal perspectives of dihydropyrimidinones: A review

Towards Enzyme‐like, Sustainable Catalysis: Switchable, Highly Efficient Asymmetric Synthesis of Enantiopure Biginelli Dihydropyrimidinones or Hexahydropyrimidinones

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