- Novel juglone and plumbagin 5-O derivatives and their in vitro growth inhibitory activity against apoptosis-resistant cancer cells
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Juglone 1 an plumbagin 2 are plant secondary metabolites nowadays well known for their anticancer properties. In this study we synthesized analogues of 1 and 2 deriving from the functionalization of the OH group in position 5 with different side chains in form of esters and ethers. Therefore the growth inhibitory activities of these adducts were evaluated in vitro on six cancer cell lines using the MTT colorimetric assays along with the two natural parent compounds. The data revealed that these latter displayed the strongest growth inhibitory activities in vitro. Quantitative videomicroscopy analyses were then carried out on human U373 glioblastoma cells, which are characterized by various level of resistance to pro-apoptotic stimuli. We compared the naturally occurring reference compounds 1 and 2 with the derivatives exerting the best activities in terms of IC50 growth inhibitory values. These analyses showed that both juglone and plumbagin had a cytostatic effect on U373 cells and were able to overcome the intrinsic resistance of U373 cancer cells to pro-apoptotic stimuli.
- Fiorito, Serena,Genovese, Salvatore,Taddeo, Vito Alessandro,Mathieu, Véronique,Kiss, Robert,Epifano, Francesco
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Read Online
- Antimalarial naphthoquinones from Nepenthes thorelii
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Roots of Nepenthes thorelii yielded plumbagin, 2-methylnaphthazarin, octadecyl caffeate, isoshinanolone, and droserone. In addition, seven derivatives were prepared from plumbagin. Each of these natural and semisynthetic compounds was evaluated for in vitro antimalarial potential.
- Likhitwitayawuid, Kittisak,Kaewamatawong, Rawiwun,Ruangrungsi, Nijsiri,Krungkrai, Jerapan
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Read Online
- Synthesis of 2-Alkyl-1,4-naphthoquinones via an ortho-Directive Metalation
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Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) has been shown to have a potent insect ecdysis inhibitory activity.To test the activity of synthetic analogs, the synthesis of 2-alkyl-1,4-naphthoquinones via an ortho-directive metalation using naphthol methoxymethyl ether as a directive group was carried out.This method is also applicable to the synthesis of naphthoquinones having unsaturated side-chain.
- Kamikawa, Tadao,Kubo, Isao
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Read Online
- Bisketene Equivalents as Diels-Alder Dienes
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2,5-Bis(tert-butyldimethylsilyloxy)furans are established as vicinal bisketene equivalents for application as dienes in the Diels-Alder reaction. Cycloaddition with olefinic dienophiles, under exceptionally mild conditions, enables convergent access to highly substituted para-hydroquinones in unprotected form via a one-pot Diels-Alder/ring-opening/tautomerization sequence. The synthesis of para-benzoquinones from acetylenic dienophiles, including benzynes, is also demonstrated, and 2,5-bis(tert-butyldimethylsilyloxy)pyrroles are established as competent dienes for the synthesis of para-iminoquinones. Application in natural product synthesis enables gram-scale access to the neuroprotective agent (±)-indanostatin.
- Dissanayake, Isuru,Hart, Jacob D.,Becroft, Emma C.,Sumby, Christopher J.,Newton, Christopher G.
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supporting information
p. 13328 - 13333
(2020/09/03)
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- Highly Efficient Synthesis and Structure–Activity Relationships of a Small Library of Substituted 1,4-Naphthoquinones
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A platform of highly efficient synthetic methodologies has been established to access a focused library of substituted 1,4-naphthoquinones derivatives functionalized with a diversity of amino/hydroxy/alkyl groups. Furthermore, the structure–activity relationship deduced from antiproliferative activities and toxicities of this 1,4-naphthoquinone library and intracellular reactive oxygen species (ROS) level detections might warrant future potential of plumbagin (2) and compound 13 as promising basic structures to develop novel anti-cancer agents.
- Bao, Na,Ou, Jinfeng,Shi, Wei,Li, Na,Chen, Li,Sun, Jianbo
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supporting information
p. 2254 - 2258
(2018/06/04)
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- Rhodium-catalyzed C-H bond activation for the synthesis of quinonoid compounds: Significant Anti-Trypanosoma cruzi activities and electrochemical studies of functionalized quinones
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Thirty four halogen and selenium-containing quinones, synthesized by rhodium-catalyzed C-H bond activation and palladium-catalyzed cross-coupling reactions, were evaluated against bloodstream trypomastigotes of T.?cruzi. We have identified fifteen compounds with IC50/24?h values of less than 2?μM. Electrochemical studies on A-ring functionalized naphthoquinones were also performed aiming to correlate redox properties with trypanocidal activity. For instance, (E)-5-styryl-1,4-naphthoquinone 59 and 5,8-diiodo-1,4-naphthoquinone 3, which are around fifty fold more active than the standard drug benznidazole, are potential derivatives for further investigation. These compounds represent powerful new agents useful in Chagas disease therapy.
- Jardim, Guilherme A.M.,Silva, Thaissa L.,Goulart, Marilia O.F.,de Simone, Carlos A.,Barbosa, Juliana M.C.,Salom?o, Kelly,de Castro, Solange L.,Bower, John F.,da Silva Júnior, Eufranio N.
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supporting information
p. 406 - 419
(2017/05/19)
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- COMPOSITIONS AND METHODS FOR TREATMENT OF PROSTATE CARCINOMA
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Disclosed herein are 1,4-naphthoquinone analogs, pharmaceutical compositions that include one or more of such 1,4-naphthoquinone analogs, and methods of treating and/or ameliorating diseases and/or conditions associated with a cancer, such as prostate can
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Paragraph 0272-0273
(2016/06/01)
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- Synthesis of Vitamin K and Related Naphthoquinones via Demethoxycarbonylative Annulations and a Retro-Wittig Rearrangement
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Anionic annulations of 3-nucleofugal phthalides with α-alkyl(aryl)acrylates involving a demethoxycarbonylation provide a succinct synthesis of vitamin K and related naphthoquinones. Also reported is a new cascade reaction stemming from a Cope-retro-Wittig rearrangement. This cascade leads to direct formation of 1-hydroxy-4-prenyloxynaphthalene-2-carboxylates from the corresponding α-prenyl acrylate acceptors.
- Mal, Dipakranjan,Ghosh, Ketaki,Jana, Supriti
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supporting information
p. 5800 - 5803
(2015/12/11)
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- Tetracycline analogues with a selective inhibitory effect on HIF-1α
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As part of a programme to discover novel transcription factor inhibitors, a 40-membered library of tetracycline analogues was screened to identify potential HIF-1 inhibitors. Two novel analogues (5b and 5c) with significant HIF-1 modulation properties were identified. These molecules possess good cellular penetration properties, and provide significant down-regulation of VEGF in U251 cells.
- Bendiabdellah,Rahman,Uranchimeg,Nahar,Antonow,Shoemaker,Melillo,Zinzalla,Thurston
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supporting information
p. 923 - 926
(2014/07/08)
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- Synthesis and SAR study of novel anticancer and antimicrobial naphthoquinone amide derivatives
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A series of novel naphthoquinone amide derivatives of the bioactive quinones, plumbagin, juglone, menadione and lawsone, with various amino acids were synthesized. The compounds were characterized by 1H NMR, 13C NMR, Mass, IR and ele
- Sreelatha, Thonthula,Kandhasamy, Subramani,Dinesh, Raghu,Shruthy, Suresh,Shweta, Sinha,Mukesh, Doble,Karunagaran, Devarajan,Balaji, Ravichandran,Mathivanan, Narayanasamy,Perumal, Paramasivan Thirumalai
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supporting information
p. 3647 - 3651
(2014/07/22)
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- Synthesis and insect antifeedant activity of plumbagin derivatives
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Napthaquinones have received considerable interest in agricultural chemistry because of a novel action mode, extremely high activity against a broad spectrum of insects, low acute toxicity to mammals, and environmentally benign characteristics. A series of plumbagin derivatives (3a-3o) were synthesized under mild esterification conditions in straightforward procedure. The structures of all new compounds were confirmed by NMR, IR, MS, and HREIMS analyses. The plumbagin derivatives were screened for their insecticidal activities against tobacco caterpillar (Spodoptera litura) and castor semilooper (Achaea janata) using a no-choice laboratory bioassay. The results show that some of the title compounds exhibit excellent antifeedant activities against 3rd instar larvae of A. janata and S. litura. The improvement in antifeedant activity requires a reasonable combination of substituents in the parent structure, which provides some hints for further investigation on structure modification. Springer Science+Business Media, LLC 2011.
- Prasad, K. Rajendra,Babu, K. Suresh,Rao, R. Ranga,Suresh,Rekha,Murthy, J. Madhusudana,Rani, P. Usha,Rao, J. Madhusudana
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experimental part
p. 578 - 583
(2012/08/07)
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- Synthesis and insect antifeedant activity of plumbagin derivatives with the amino acid moiety
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A series of plumbagin derivatives (4a-4k) containing an amino acid moiety were synthesized under mild esterification conditions in excellent yields (35%-80%) and screened for their antifeedant activities in tobacco caterpillar (Spodoptera lltura) and cast
- Sreelatha, Thonthula,Hymavathi, Atmakur,Babu, Katragadda Suresh,Murthy, Joish Madhusudana,Pathipati, Usha Rani,Rao, Janaswamy Madhusudana
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experimental part
p. 6090 - 6094
(2010/07/02)
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- Total synthesis of (±)-plumbazeylanone, a naphthoquinone trimer from Plumbago zeylanica
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We have investigated the total synthesis of (±)-plumbazeylanone (1), a naphthoquinone trimer based on two different pathways (I) and (II). The synthetic approach based on pathway (I) was not successful. However, the first synthesis of 1 from plumbagin (2a) was achieved by utilizing an unsymmetrical methylene-bridged dimer (20b), with a naphthoquinone unit and a naphthalene unit as a key intermediate, based on pathway (II), in 11 steps with an overall yield of 5.9%. This synthesis features regioselective nucleophilic 1,2-addition of the naphthyllithium reagent 4a to the C-1 position of naphthoquinone 20b, and the regio- and stereoselective dienonephenol-type rearrangement of the 1,2-adduct 21b (1,2-migration of the naphthyl group to the C3-position on 21b) with 2 N-NaOH.
- Takeya, Tetsuya,Kajiyama, Manabu,Nakamura, Chikara,Tobinaga, Seisho
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p. 209 - 219
(2007/10/03)
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- Total synthesis of (±)-plumbazeylanone
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The first total synthesis of plumbazeylanone (1), which is a trimer of naphthoquinone, was carried out successfully utilizing the unsymmetrical methylene-bridged dimer with the naphthoquinone unit and the naphthol unit, 11b as a key intermediate in 11 steps. This synthesis features a regioselective nucleophilic 1,2-addition reaction and dienone-phenol-type rearrangement.
- Takeya, Tetsuya,Kajiyama, Manabu,Nakamura, Chikara,Tobinaga, Seisho
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p. 1660 - 1661
(2007/10/03)
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- Reactions of naturally occurring α-naphthoquinone: Part I
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The reactions of plumbagin (5-hydroxy-2-methyl-naphthalene-1,4-dione), an active principle of Plumbago species, with bromine, hydrogen cyanide and nitrous acid have been studied and the bromo, cyano and nitro compounds isolated from the reaction products have been characterized and their structures determined from their spectral data (UV-VIS, IR, 1H NMR, 13C NMR and MS).
- Dinda, B.,Chel, G.,Saha, S.,Patra, A.
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p. 502 - 506
(2007/10/02)
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- A Strategy for Generalization of the Regiospecific Synthesis of Substituted Quinones from Cyclobutenediones
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Documented within is a straightforward protocol for the synthesis of generally substituted benzoquinones and ring-fused quinones.Previously, the crucial issue of quinone substituent regiochemistry was resolved at the stage of addition of an unsaturated carbon nucleophile to a cyclobutenedione by using either symmetrically substituted cyclobutenediones or 3-alkoxy (or amino)-4-substituted-3-cyclobutenediones.In the former case there are no regioisomeric quinones formed, while in the latter, through resonance delocalization, the alkoxy (or amino) substituent renders one of the two carbonyl groups less reactive and directs the incoming nucleophile to the other.The placement of a wide variety of substituents about the quinone ring periphery has now been solved by the less restrictive strategy of sequential introduction of substituents onto a cyclobutenedione core.The chemistry commences with 3-isopropoxy-4-substituted-3-cyclobutene-1,2-diones.Addition of an aromatic, heteroaromatic, or alkenyl nucleophile to the more reactive carbonyl group provides 4-hydroxy-4-Runsat-2-cyclobutenones, which are protected as the methyl ethers by treatment with MeI/Ag2O/K2CO3 in MeCN.A second nucleophile is added, again in a 1,2-sense, providing highly substituted 3-isopropoxy-2-cyclobutenols that are arranged to cyclobutenones under acidic conditions.The resulting cyclobutenones are converted into substituted quinones by thermolysis at 140 deg C in o-xylene followed by oxidative workup with ceric ammonium nitrate.The substitution pattern about the quinone core is rigorously controlled by the sequence of introduction of the substituents.
- Liebeskind, Lanny S.,Granberg, Kenneth L.,Zhang, Jing
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p. 4345 - 4352
(2007/10/02)
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- Naphthalene anti-psoriatic agents
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Psoriasis in mammals is relieved by topically administering naphthalenes of the formula: STR1 wherein: R1 is lower alkoxy or optionally substituted phenoxy; R2 is hydrogen, lower alkyl, optionally substituted phenyl or optionally substituted phenyl-lower-alkyl; R3 is hydrogen, lower alkyl, lower alkoxy, halo, optionally substituted phenyl, optionally substituted phenyl-lower-alkyl or optionally substituted phenyl-lower-alkoxy, and m is 1 or 2; X and Y are different and are selected from the group consisting of hydrogen, R4 and -C(O)W, wherein W is alkyl of one to seven carbon atoms, optionally substituted phenyl or optionally substituted benzyl; and R4 is lower alkyl or optionally substituted phenyl-lower-alkyl.
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- METHOD FOR TREATING DISEASE STATES IN MAMMALS WITH NAPHTHALENE LIPOXYGENASE-INHIBITTNG AGENTS
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Psoriasis in mammals is relieved by topically administering naphthalenes of the formula: wherein: R1 is lower alkoxy or optionally substituted phenoxy, R2 is the same as R1, or R2 is hydrogen, lower alkyl, optionally substituted phenyl or optionally substituted phenylalkyl, R3 is hydrogen, lower alkyl, lower alkoxy, halo, optionally substituted phenyl, optionally substituted phenyl-lower-alkyl or optionally substituted phenyl-lower-alkoxy, and m is 1 or 2; both X groups are the same and X is either -C(O)OR4 or -C(O)NR5R6 , wherein R4 is alkyl, phenyl or benzyl optionally substituted with one or two lower alkyl groups, lower alkoxy groups or halo; and R5 and R6 are independently hydrogen, lower alkyl, cycloalkyl or phenyl optionally substituted with one or two lower alkyl groups, lower alkoxy groups or halo. The compounds of this invention are also useful for the treatment of disease-states caused by lipoxygenase activity in mammals, particularly 5-lipoxygenase activity, when administered systemically.
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- Naphthalene lipoxygenase-inhibiting agents
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Psoriasis in mammals is relieved by topically administering naphthalenes of the formula: STR1 wherein: R1 is lower alkoxy or optionally substituted phenoxy; R2 is hydrogen, lower alkyl, optionally substituted phenyl or optionally substituted phenylalkyl; R3 is hydrogen, lower alkyl, lower alkoxy, halo, optionally substituted phenyl, optionally substituted phenyl-lower-alkyl or optionally substituted phenyl-lower-alkoxy, and m is 1 or 2; X and Y are different and are either R4 or --C(O)W wherein R4 is lower alkyl or optionally substituted phenyl-lower-alkyl; W is --OR5 or --NR6 R7, wherein R5 is alkyl, optionally substituted phenyl or optionally substituted benzyl; and R6 and R7 are independently hydrogen, lower alkyl, cycloalkyl or optionally substituted phenyl. The compounds of this invention are also useful for the treatment of disease-states caused by lipoxygenase activity in mammals, particularly 5-lipoxygenase activity, when administered systemically.
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- Studies on Medicinal and Related Plants of Sri Lanka. Part 18. Structure of a New Naphthoquinone from Plumbago zeylanica.
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The isolation of chitranone (3), zeylanone (4), maritinone (5), 2-methylnaphthazarin (6), plumbazeylanone, and a new naphthoquinone, methylene-3,3'diplumbagin (7), from the phenolic fraction of the light petroleum extract of the roots of Plumbago zeylanica (Plumbaginaceae) is reported.The dimethyl ether of the new quinone has been synthesized from plumbagin methyl ether.
- Gunaherath, G.M. Kamal B.,Gunatilaka, A.A. Leslie,Thompson, Ronald H.
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p. 407 - 410
(2007/10/02)
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- Naphthalene anti-psoriatic agents
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Psoriasis in mammals is relieved by topically administering naphthalenes of the formula: STR1 wherein: R1 is lower alkoxy or optionally substituted phenoxy; R2 is hydrogen, lower alkyl, optionally substituted phenyl or optionally substituted phenylalkyl; R3 is hydrogen, lower alkyl, lower alkoxy, halo, optionally substituted phenyl, optionally substituted phenyl-lower-alkyl or optionally substituted phenyl-lower-alkoxy, and m is 1 or 2; X and Y are different and are either R4 or --C(O)W wherein R4 is lower alkyl or optionally substituted phenyl-lower-alkyl; W is --OR5 or --NR6 R7, wherein R5 is alkyl, optionally substituted phenyl or optionally substituted benzyl; and R6 and R7 are independently hydrogen, lower alkyl, cycloalkyl or optionally substituted phenyl.
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- Catalytic Asymmetric Induction in Oxidation Reactions. Synthesis of Optically Active Epoxynaphthoquinones
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Optically active 2,3-epoxides of a variety of substituted 1,4-naphthoquinones have been prepared in an asymmetric synthesis.Enantiomeric excess of up to 45percent were realized.Some data could be obtained concerning the influence of substituents on the en
- Pluim, Henk,Wynberg, Hans
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p. 2498 - 2502
(2007/10/02)
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