Mercuric acetate oxidation of isolapachol

Dudley, Kenneth H.; Miller, H. Wayne

doi:10.1021/jo01282a054

Cited by 21 publications

(8 citation statements)

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“…Alternatively, milder reaction conditions, i.e. diluted hydrochloric acid, 65 °C and 15 min of reaction time, were used to obtain 4g , 4h , and 4i [ 16 ]. Cycloaddition reactions of 4 with different reagents were carried out to obtain the compounds 4j – 4t .…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Anti-Proliferative Activity Evaluation and 3D-QSAR Study of Naphthoquinone Derivatives as Potential Anti-Colorectal Cancer Agents

et al. 2018

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Colorectal cancer (CRC) is a disease with high incidence and mortality, constituting the fourth most common cause of death from cancer worldwide. Naphthoquinones are attractive compounds due to their biological and structural properties. In this work, 36 naphthoquinone derivatives were synthesized and their activity evaluated against HT-29 cells. Overall, high to moderate anti-proliferative activity was observed in most members of the series, with 15 compounds classified as active (1.73 < IC50 < 18.11 μM). The naphtho[2,3-b]thiophene-4,9-dione analogs showed potent cytotoxicity, 8-hydroxy-2-(thiophen-2-ylcarbonyl)naphtho[2,3-b]thiophene-4,9-dione being the compound with the highest potency and selectivity. Our results suggest that the toxicity is improved in molecules with tricyclic naphtho[2,3-b]furan-4,9-dione and naphtho[2,3-b]thiophene-4,9-dione systems 2-substituted with an electron-withdrawing group. A 3D-QSAR study of comparative molecular field analysis (CoMFA) was carried out, resulting in the generation of a reliable model (r2 = 0.99 and q2 = 0.625). This model allowed proposing five new compounds with two-fold higher theoretical anti-proliferative activity, which would be worthwhile to synthesize and evaluate. Further investigations will be needed to determine the mechanism involved in the effect of most active compounds which are potential candidates for new anticancer agents.

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Section: Resultsmentioning

confidence: 99%

Synthesis, Anti-Proliferative Activity Evaluation and 3D-QSAR Study of Naphthoquinone Derivatives as Potential Anti-Colorectal Cancer Agents

et al. 2018

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“…The HNQs ( 6a–h ) were synthesized by aldol condensation between commercial lawsone ( 5 ) (Sigma-Aldrich) and appropriate aldehydes, according to a methodology adapted from Hooker [ 59 ] with yields ranging from 32% to 91% ( Scheme 1 ). The FNQs 7a–h and 8a–h were prepared by oxidative cyclization of the corresponding HNQs with Hg(OAc) 2 [ 20 , 34 , 60 ], as outlined in Scheme 1 . When the reaction mixtures were diluted with HCl 2N for 15 min, ortho- FNQs (kinetic products) were the major products, while when concentrated HCl (12N) was used with 3 h of reaction, para- FNQs (thermodynamic products) were obtained [ 60 ].…”

Section: Resultsmentioning

confidence: 99%

“…The FNQs 7a–h and 8a–h were prepared by oxidative cyclization of the corresponding HNQs with Hg(OAc) 2 [ 20 , 34 , 60 ], as outlined in Scheme 1 . When the reaction mixtures were diluted with HCl 2N for 15 min, ortho- FNQs (kinetic products) were the major products, while when concentrated HCl (12N) was used with 3 h of reaction, para- FNQs (thermodynamic products) were obtained [ 60 ]. The ortho- and para- FNQs were obtained with yields ranging from 20% to 92% ( Scheme 1 ).…”

Section: Resultsmentioning

confidence: 99%

Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits

Borgati

Nascimento

Bernardino

et al. 2017

Journal of Tropical Medicine

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A total of 28 lapachol-related naphthoquinones with four different scaffolds were synthesized and spectroscopically characterized. In vitro antiplasmodial activity was assayed against the chloroquine-resistant Plasmodium falciparum W2 strain by the parasite lactate dehydrogenase (pLDH) method. Cytotoxicity against Hep G2A16 cell was determined by the MTT assay. All compounds disclosed higher in vitro antiplasmodial activity than lapachol. Ortho- and para-naphthoquinones with a furan ring fused to the quinonoid moiety were more potent than 2-hydroxy-3-(1′-alkenyl)-1,4-naphthoquinones, while ortho-furanonaphthoquinones were more cytotoxic. Molecular docking to Plasmodium targets Pfcyt bc1 complex and PfDHOD enzyme showed that five out of the 28 naphthoquinones disclosed favorable binding energies. Furanonaphthoquinones endowed with an aryl moiety linked to the furan ring are highlighted as new in vitro antiplasmodial lead compounds and warrant further investigation.

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“…The synthesis of 4, 5 and 4, 9-furanonaphthoquinone was carried out in two steps using the synthetic pathways previously reported by Hooker (Hooker, 1936), and Dudley and Miller (Dudley and Miller, 1967). The first step consisted on nucleophilic addition using 2-hydroxyl-1,4-naphthoquinone and an aldehyde (propionaldehyde, butanaldehyde, or hexanaldehyde) dissolved in acetic acid at 60°C, which produced an intermediary compound (2 -hydroxyl -3alkenyl -1, 4 -naphthoquinone) specific for each aldehyde used.…”

Section: Synthesismentioning

confidence: 99%

Synthetic alkyl substituted quinones oxidize membrane proteins and arrest Plasmodium falciparum growth in vitro

Lengua¹,

Kamali²,

Cano³

et al. 2015

Afr. J. Pharm. Pharmacol.

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Quinones are a family of bioactive compounds with known antibacterial, antiviral and antiparasitic activity. The capacity of quinoid compounds to accept electrons, due to electron-attracting (or donating) substituents at the quinone moiety, modulates their redox activity upon interaction with biological systems. Nine quinone derivate including three 2-hydroxyl-1, 4-naphthoquinone; three 4,5-and three 4,9-naphthoquinone scaffolds, were synthesized and evaluated against 3D7 and Dd2 Plasmodium falciparum strains and evaluated the oxidative stress. Cell viability was determined MTTrelated colorimetric assay (EZ4u; Biomedical, Austria). Selectivity of these compounds was evaluated by comparing in vitro, of cytotoxicity in human fibroblast and antimalarial activity in Plasmodium falciparum. Peripheral blood mononuclear cells and hemoglobin release from human erythrocytes were evaluated too. Antiplasmodial activity was evaluated by fluorometry methods. In addition, oxidized membrane protein in the malaria parasite was evaluated in vitro by derivatizatión, after treatment at IC 50 values on P. falciparum Dd2 strain. Quinones showed IC 50 values in the micromole range, selectivity indexes for quinones was variable, compounds 2 and 3 showed excellent selectivity. In vitro antiplasmodial activity was showed; this result is an incentive to continue synthesis and studying the quinoid compounds.

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Mercuric acetate oxidation of isolapachol

Cited by 21 publications

References 1 publication

Synthesis, Anti-Proliferative Activity Evaluation and 3D-QSAR Study of Naphthoquinone Derivatives as Potential Anti-Colorectal Cancer Agents

Synthesis, Anti-Proliferative Activity Evaluation and 3D-QSAR Study of Naphthoquinone Derivatives as Potential Anti-Colorectal Cancer Agents

Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits

Synthetic alkyl substituted quinones oxidize membrane proteins and arrest Plasmodium falciparum growth in vitro

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