Quinonoid compounds via reactions of lawsone and 2-aminonaphthoquinone with α-bromonitroalkenes and nitroallylic acetates: Structural diversity by C-ring modification and cytotoxic evaluation against cancer cells

Baiju, Thekke V.; Almeida, Renata G.; Sivanandan, Sudheesh T.; Simone, C. A. De; Brito, Lucas Moreira; Cavalcanti, Bruno C.; Pessoa, Cláudia; Namboothiri, Irishi N. N.; Júnior, Eufrânio N. da Silva

doi:10.1016/j.ejmech.2018.03.079

Cited by 45 publications

(18 citation statements)

References 119 publications

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“…Group 2 is composed of para-quinones. We studied compounds such as αlapachones [60,72], arylamino derivatives [60,64,71], furanonaphthoquinones [73][74][75],…”

Section: Assembly Of a Chemical Library For Virtual Screening Against Mpromentioning

confidence: 99%

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Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2

Santos¹,

Kronenberger

Almeida

et al. 2022

Preprint

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The worldwide COVID-19 pandemic caused by the coronavirus SARS-CoV-2 urgently demands novel direct antiviral treatments. The main protease (Mpro) and papain-like protease (PLpro) are attractive drug targets among coronaviruses due to their essential role in processing the polyproteins translated from the viral RNA. In the present work, we virtually screened 688 naphthoquinoidal compounds and derivatives against Mpro of SARS-CoV-2. Twenty-four derivatives were selected and evaluated in biochemical assays against Mpro using a novel fluorogenic substrate. In parallel, these compounds were also assayed with SARS-CoV-2 PLpro. Four compounds inhibited Mpro with half-maximal inhibitory concentration (IC50) values between 0.41 μM and 66 μM. In addition, eight compounds inhibited PLpro with IC50 ranging from 1.7 μM to 46 μM. Molecular dynamics simulations suggest stable binding modes for Mpro inhibitors with frequent interactions with residues in the S1 and S2 pockets of the active site. For two PLpro inhibitors, interactions occur in the S3 and S4 pockets. In summary, our structure-based computational and biochemical approach identified novel naphthoquinonal scaffolds that can be further explored as SARS-CoV-2 antivirals.

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“…Group 2 is composed of para-quinones. We studied compounds such as αlapachones [60,72], arylamino derivatives [60,64,71], furanonaphthoquinones [73][74][75],…”

Section: Assembly Of a Chemical Library For Virtual Screening Against Mpromentioning

confidence: 99%

“…and pyrrolonaphthoquinones [73,76], in addition to other derivatives based on paraquinones [64,75]. The selected compounds for this group exhibit a broad substitution pattern but, in general, arylamino and aryl groups are often observed.…”

Section: Assembly Of a Chemical Library For Virtual Screening Against Mpromentioning

confidence: 99%

Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2

Santos¹,

Kronenberger

Almeida

et al. 2022

Preprint

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“…A number of synthetic aminoisoquinolinequinones and polycyclic analogs have been the subject of study for many years due to their in vitro cytotoxic activities on several cancer cell lines [33,34,35,36,37,38,39]. A well-established procedure to prepare alkyl- and arylaminoquinones is based on the oxidative coupling reaction of quinones with alkyl- and arylamines [40,41,42,43,44].…”

Section: Introductionmentioning

confidence: 99%

Green Synthesis and Electrochemical Properties of Mono- and Dimers Derived from Phenylaminoisoquinolinequinones

et al. 2019

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In the search for new quinoid compounds endowed with potential anticancer activity, the synthesis of novel heterodimers containing the cytotoxic 7-phenylaminoisoquinolinequinone and 2-phenylaminonaphthoquinone pharmacophores, connected through methylene and ethylene spacers, is reported. The heterodimers were prepared from their respective isoquinoline and naphthoquinones and 4,4′-diaminodiphenyl alkenes. The access to the target heterodimers and their corresponding monomers was performed both through oxidative amination reactions assisted by ultrasound and CeCl3·7H2O catalysis “in water”. This eco-friendly procedure was successfully extended to the one-pot synthesis of homodimers derived from the 7-phenylaminoisoquinolinequinone pharmacophore. The electrochemical properties of the monomers and dimers were determined by cyclic and square wave voltammetry. The number of electrons transferred during the oxidation process, associated to the redox potential EI1/2, was determined by controlled potential coulometry.

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“…[11,12] This moiety is present as an important core in an umber of cytotoxic agents, such as naturallyo ccurring caulibugulones of type I ( Figure 1), which were found to exhibit IC 50 values of 0.03-1.67 mm against murinet umor cells. [11,12] This moiety is present as an important core in an umber of cytotoxic agents, such as naturallyo ccurring caulibugulones of type I ( Figure 1), which were found to exhibit IC 50 values of 0.03-1.67 mm against murinet umor cells.…”

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confidence: 99%

“…Isoquinoline-5,8-diones have indeed been shown to display aw ide range of biological activities such as antibacterial, antifungal, antimalarial, and antitumor. [11,12] This moiety is present as an important core in an umber of cytotoxic agents, such as naturallyo ccurring caulibugulones of type I ( Figure 1), which were found to exhibit IC 50 values of 0.03-1.67 mm against murinet umor cells. [13] Moreover,p ixantrone (II), an aza-anthraquinone commercialized under the trade name Pixuvri,i sa n antineoplastic drug that has completed phase III clinicalt rials and stands in the family of antitumora ntibiotics for the treatment of different types of cancers.…”

mentioning

confidence: 99%

Quinone‐Fused Pyrazoles through 1,3‐Dipolar Cycloadditions: Synthesis of Tricyclic Scaffolds and in vitro Cytotoxic Activity Evaluation on Glioblastoma Cancer Cells

et al. 2018

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A novel and straightforward synthesis of highly substituted isoquinoline-5,8-dione fused tricyclic pyrazoles is reported. The key step of the synthetic sequence is a regioselective, Ag CO promoted, 1,3-dipolar cycloaddition of C-heteroaryl-N-aryl nitrilimines and substituted isoquinoline-5,8-diones. The broad functional group tolerability and mild reaction conditions were found to be suitable for the preparation of a small library of compounds. These scaffolds were designed to interact with multiple biological residues, and two of them, after brief synthetic elaborations, were analyzed by molecular docking studies as potential anticancer drugs. In vitro studies confirmed the potent anticancer effects, showing promising IC values as low as 2.5 μm against three different glioblastoma cell lines. Their cytotoxic activity was finally positively correlated to their ability to inhibit PI3K/mTOR kinases, which are responsible for the regulation of diverse cellular processes in human cancer cells.

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Quinonoid compounds via reactions of lawsone and 2-aminonaphthoquinone with α-bromonitroalkenes and nitroallylic acetates: Structural diversity by C-ring modification and cytotoxic evaluation against cancer cells

Cited by 45 publications

References 119 publications

Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2

Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2

Green Synthesis and Electrochemical Properties of Mono- and Dimers Derived from Phenylaminoisoquinolinequinones

Quinone‐Fused Pyrazoles through 1,3‐Dipolar Cycloadditions: Synthesis of Tricyclic Scaffolds and in vitro Cytotoxic Activity Evaluation on Glioblastoma Cancer Cells

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