Synthesis, Molecular Modelling and Anticancer Activities of New Molecular Hybrids Containing 1,4-Naphthoquinone, 7-Chloroquinoline, 1,3,5-Triazine and Morpholine Cores as PI3K and AMPK Inhibitors in the Metastatic Melanoma Cells

Fiorot, Rodolfo G.; Westphal, Regina; Lemos, Bárbara C.; Romagna, Rodrigo A.; Gonçalves, Paola Rocha; Fernandes, Maruska R. N.; Ferreira, Carmen V.; Taranto, Alex Gutterres; Greco, Sandro J.

doi:10.21577/0103-5053.20190096

Cited by 9 publications

(12 citation statements)

References 39 publications

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“…Having both, the nucleophilic derivative 6 and the electrophilic intermediate 9, the molecular hybrid 1 was obtained as a yellow solid in 34% yield by reacting 6 with 9 in acetonitrile for 16 hours, under reflux in the presence of triethylamine ( Figure 5) [23]. Two important peaks were observed in the mass spectrum of 1: one in the mass/charge ratio of 480.23549 m/z (error of −0.23 ppm), related to the protonated species; and one in the mass/charge ratio of 959.46450 m/z (error of −1.06 ppm), associated to the protonated dimer.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis and Evaluation of Corrosion Inhibiting Activity of New Molecular Hybrids Containing the Morpholine, 1,4-Naphthoquinone, 7-Chloroquinoline and 1,3,5-Triazine Cores

Westphal¹,

Pina²,

Franco³

et al. 2020

ACES

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Three molecules containing morpholine, 1,4-naphthoquinone, 7-chloroquinoline and 1,3,5-triazine cores, scaffolds with recognized anti-corrosive activity, were synthesized and had their anticorrosive activity evaluated through potentiodynamic polarization and electrochemical impedance studies. Both studies were conducted in a simulated production water medium containing 150,000 mg•L −1 Cl − and 5 mg•L −1 S 2−. Corrosion inhibition efficiency ranged from 67%-86%, amongst which the naphthoquinone-containing derivative (compound 1) was the most effective. These compounds act through formation of a protective film on the surface of AISI 316 stainless steel. Investigation of the molecular properties of the prepared inhibitors by DFT calculations revealed that the LUMO energy and chemical hardness of the molecules can be directly correlated with their inhibition efficiency.

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Section: Resultsmentioning

confidence: 99%

“…However, some solubility-related problems are common in triazine derivatives, affecting synthesis, characterization, and application steps. To increase its derivatives solubility, the insertion of morpholine group in the triazine core has shown to be a good strategy [23] [24].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Corrosion Inhibiting Activity of New Molecular Hybrids Containing the Morpholine, 1,4-Naphthoquinone, 7-Chloroquinoline and 1,3,5-Triazine Cores

Westphal¹,

Pina²,

Franco³

et al. 2020

ACES

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“…Compounds 32 and 33 (Figure 9) demonstrated IC50 values within the range of 5 to 9 µM. An in vivo test on a zebrafish proved the non-toxicity of compounds 32 and 33 [35].…”

Section: Primary Anticancer Studiesmentioning

confidence: 95%

“…Analog 61 had an IC 50 value of approximately 25 µM when exposed to the SKMEL-103 (N-RAS mutated) cell line. A Western blot determined the decreased expression of both PI3Kγ and AMPK [35].…”

Section: Primary Anticancer Studiesmentioning

confidence: 99%

Recent Advances in the Biological Activity of s-Triazine Core Compounds

Maliszewski

Drozdowska

2022

Pharmaceuticals

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An effective strategy for successful chemotherapy relies on creating compounds with high selectivity against cancer cells compared to normal cells and relatively low cytotoxicity. One such approach is the discovery of critical points in cancer cells, i.e., where specific enzymes that are potential therapeutic targets are generated. Triazine is a six-membered heterocyclic ring compound with three nitrogen replacing carbon-hydrogen units in the benzene ring structure. The subject of this review is the symmetrical 1,3,5-triazine, known as s-triazine. 1,3,5-triazine is one of the oldest heterocyclic compounds available. Because of its low cost and high availability, it has attracted researcher attention for novel synthesis. s-Triazine has a weak base, it has much weaker resonance energy than benzene, therefore, nucleophilic substitution is preferred to electrophilic substitution. Heterocyclic bearing a symmetrical s-triazine core represents an interesting class of compounds possessing a wide spectrum of biological properties such as anti-cancer, antiviral, fungicidal, insecticidal, bactericidal, herbicidal and antimicrobial, antimalarial agents. They also have applications as dyes, lubricants, and analytical reagents. Hence, the group of 1,3,5-triazine derivatives has developed over the years. Triazine is not only the core amongst them, but is also a factor increasing the kinetic potential of the entire derivatives. Modifying the structure and introducing new substituents makes it possible to obtain compounds with broad inhibitory activity on processes such as proliferation. In some cases, s-triazine derivatives induce cell apoptosis. In this review we will present currently investigated 1,3,5-triazine derivatives with anti-cancer activities, with particular emphasis on their inhibition of enzymes involved in the process of tumorigenesis.

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“…Lawsone, 4,7-dichloroquinoline, cyanuric chloride, and morpholine were used by Fiorot et al [ 30 ] to synthesize three hybrids whose structures were designed based on docking calculation considering the interaction of the lead compound with the phosphoinositide 3-kinase and the 5′ AMP-activated protein kinase. Product 6 resulted to be the most cytotoxic towards human melanoma SKMEL-103 cells, whereas 7 showed no activity ( Figure 4 ).…”

Section: Design Synthesis and Biological Evaluation Of Antitumor Hybridsmentioning

confidence: 99%

Hybrid Molecules Containing Naphthoquinone and Quinolinedione Scaffolds as Antineoplastic Agents

et al. 2022

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In recent decades, molecular hybridization has proven to be an efficient tool for obtaining new synthetic molecules to treat different diseases. Based on the core idea of covalently combining at least two pharmacophore fragments present in different drugs and/or bioactive molecules, the new hybrids have shown advantages when compared with the compounds of origin. Hybridization could be successfully applied to anticancer drug discovery, where efforts are underway to develop novel therapeutics which are safer and more effective than those currently in use. Molecules presenting naphthoquinone moieties are involved in redox processes and in other molecular mechanisms affecting cancer cells. Naphthoquinones have been shown to inhibit cancer cell growth and are considered privileged structures and useful templates in the design of hybrids. The present work aims at summarizing the current knowledge on antitumor hybrids built using 1,4- and 1,2-naphthoquinone (present in natural compounds as lawsone, napabucasin, plumbagin, lapachol, α-lapachone, and β -lapachone), and the related quinolone- and isoquinolinedione scaffolds reported in the literature up to 2021. In detail, the design and synthetic approaches adopted to produce the reported compounds are highlighted, the structural fragments considered in hybridization and their biological activities are described, and the structure–activity relationships and the computational analyses applied are underlined.

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Synthesis, Molecular Modelling and Anticancer Activities of New Molecular Hybrids Containing 1,4-Naphthoquinone, 7-Chloroquinoline, 1,3,5-Triazine and Morpholine Cores as PI3K and AMPK Inhibitors in the Metastatic Melanoma Cells

Cited by 9 publications

References 39 publications

Synthesis and Evaluation of Corrosion Inhibiting Activity of New Molecular Hybrids Containing the Morpholine, 1,4-Naphthoquinone, 7-Chloroquinoline and 1,3,5-Triazine Cores

Synthesis and Evaluation of Corrosion Inhibiting Activity of New Molecular Hybrids Containing the Morpholine, 1,4-Naphthoquinone, 7-Chloroquinoline and 1,3,5-Triazine Cores

Recent Advances in the Biological Activity of s-Triazine Core Compounds

Hybrid Molecules Containing Naphthoquinone and Quinolinedione Scaffolds as Antineoplastic Agents

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