Naphthofuran Derivatives Research Articles

Synthesis, Characterization, and Interaction Studies of Naphtho‐[2,3]‐furan‐Based Molecules with CTAB as Model Surfactant

AbstractThe synthesis of highly sensitive UV–visible active naphthofuran derivatives, namely naphtho‐[2,3]‐furan‐3‐yl acetate (NF), 9‐bromonaphtho‐[2,3]‐furan‐3‐yl acetate (BNF), 9‐nitronaphtho‐[2,3]‐furan‐3‐yl acetate (NNF), 9‐iodonaphtho‐[2,3]‐furan‐3‐yl acetate (INF), and naphtho‐[2,1‐b]‐furan‐4‐carboxylic acid (ONF) as solvatochromic molecules, was carried out through multistep synthetic approach. These molecules possess different substituents that tend to form micelles in cetyl trimethylammonium bromide (CTAB) aqueous system. During the micellization process, the absorption spectrum of the synthesized molecule exhibits sensitivity towards the polarity of the environment, which affects the critical micelle concentration (cmc) of CTAB. This study demonstrates that synthesized molecules can be used for estimating solvent polarity and cmc.

Computational and biological evaluation of naphthofuran-based scaffold as an anti-inflammatory agent

Naphthofuran derivatives can reduce inflammation by inhibiting prostaglandins and cytokines. They also modulate immune cell activity and scavenge reactive oxygen species to alleviate oxidative stress-induced inflammation. In this study, we evaluated the anti-inflammatory potential of a naphthofuran-based derivative, 2-phenyl-1-(phenylthio)naphtho[2,1-b]furan (PTNF), to inhibit nitric oxide (NO) and its impact on the production of pro-inflammatory cytokines TNF-α and IL-6. In addition to 6–311++G(d,p) basis set, quantum mechanical calculations were carried out to explain the geometry and stability of the PTNF using DFT at the B3LYP level. Molecular docking investigations revealed that PTNF exhibited strong binding interactions with TNF-α and IL-6. These results emphasize the potential of naphthofuran derivatives in shaping future therapeutic approaches, specifically for addressing inflammatory diseases.

Visible-light promoted oxidative annulation of 2-naphthols with phenylglyoxal monohydrates toward hydroxy-naphthofuranone and its derivatives.

A highly efficient and innovative method involving base-mediated oxidative annulation between 2-naphthols and phenylglyoxal monohydrate under visible light irradiation has been successfully developed. This method leads to the formation of oxygen-containing heterocyclic compounds, particularly hydroxy-naphthofuranone derivatives, encompassing a unique quaternary carbon center. An X-ray diffraction study has unambiguously confirmed the structure of one such derivative. In particular, water molecules in this reaction serve various functions as a solvent, reagent, and additive, with the conversion of the process found to be influenced by the volume of water present. This atom-economical approach demonstrates tolerance for different substituents in both phenylglyoxal monohydrate and 2-naphthol, enabling the synthesis of a variety of naphthofuranones in satisfactory to good yields. The formation of a naphthofuranium cationic intermediate under acidic circumstances enables the formation of C-C or C-O bonds with a wide range of aromatic or alcoholic nucleophilic partners. Furthermore, the identification and generation of pinacol-type starting precursors from these naphthofuranone derivatives enable the synthesis of highly regioselective naphthofuran derivatives.

Construction of Functionalized ortho‐Naphthoquinone Methides via Site‐Selective Ring Opening of 1‐Siloxy‐1,4‐epoxy‐1,4‐dihydronaphthalenes

Abstract1‐Siloxy‐4‐(benzyloxy)methyl‐1,4‐epoxy‐1,4‐dihydronaphthalenes, generated from benzynes and furans, underwent automatic site‐selective ring opening because of the synergetic effect of the steric strain of the 1,4‐epoxy moiety and the electron‐donating ability of the siloxy group on the acetal structure to afford the precursors of ortho‐naphthoquinone methides (o‐NQMs). Subsequent Lewis acid‐facilitated o‐NQM formation and annulation with olefins afforded multi‐fused heterocycles. Notably, the consecutive hexacyclic skeleton of rubioncolin B was constructed via solvent‐dependent regioselective annulation of naphthofuran derivatives.

Rhodium-Catalyzed Coordination-Assisted Regioselective and Migratory Three-Point Double Annulation of o-Alkenyl Phenols with Tertiary Propargyl Alcohols.

We disclose herein a Rh(III)-catalyzed migratory three-point double annulation of o-alkenyl phenols with propargyl alcohols for de novo construction of naphtho furan derivatives in a regio- and chemoselective manner. The protocol orchestrates two new rings with four new bonds in one operation without the need for any additive. Necessary labeled and control experiments are conducted to elucidate the reaction mechanism. A tertiary hydroxyl group is found to be crucial both for controlling the regioselective insertion of alkyne through chelation with rhodium to form a key spiro cyclic intermediate and for forcing ring expansion via unusual and selective olefin reshuffling, apart from forming an extra (furan) ring. The protocol is scalable and shows tolerance for late stage functionalization of natural products.

SYNTHESIS, CHARACTERIZATION, AND ANTIBACTERIAL ACTIVITIES OF NAPHTHO[2,1-b]FURAN DERIVATIVES

The naphthofuran and its derivatives are important biological compounds so we have focused on the synthesis of naphthofuran derivatives. The synthesized compounds of ethyl 1-(acetylamino)-5-nitronaphtho[2,1-b]furan-2- carboxylate (3), and N-[2-(hydrazinylcarbonyl)-5-nitronaphtho[2,1-b]furan-1-yl]acetamide (4) used for the synthesis of N-(2-{[(2Z)-2-benzylidenehydrazinyl]carbonyl}-5-nitronaphtho[2,1-b]furan-1-yl)acetamide compounds of four derivatives 5 (a-d) and 1-acetamido-5-nitro-N-(5-oxo-2-phenylthiazolidin-3-yl)naphtha[2,1-b]furan-2-carboxamide compounds of four derivatives 6 (a-d). The prepared compounds were confirmed by FTIR NMR, and mass methods. The prepared naphthofuran derivatives used for the antibacterial activity versus both Gram(+ve) and Gram(-ve) bacteria show excellent results. Therefore the synthesized compounds are used for further antibacterial studies in the medical field.

Design, Synthesis and Pharmacological Evaluation of Naphthofuran Derivatives as Potent SIRT1 Activators.

Diabetic nephropathy (DN) is one of the most important medical complications in diabetic patients, which is an essential cause of end-stage renal disease in diabetic patients and still lacks effective medicines. Silent information regulator 1 (SIRT1) is closely related to the occurrence and development of DN. Activation of SIRT1 could significantly improve the symptoms of DN, while the activities of SIRT1 activators need to be further improved. Based on the crystal structure of SIRT1, structure and ligand-based approaches were carried out, and a lead compound 4,456–0661 (renamed as M1) was identified. Moreover, seven M1 analogues (6a-6g) were designed using a structure-based drug design strategy followed by bioactivity evaluation with SRTR2104 used as positive drugs. Among the target molecules, compounds M1, 6b, and 6d were proved to be potent SIRT1 activators, the activities of which are comparable to SRT2104. More importantly, compounds M1, 6b, and 6d could resist high glucose-induced apoptosis of HK-2 cells by activating SIRT1 and deacetylation of p53. Apart from the beneficial effect on apoptosis of DN, these compounds also alleviated high glucose stimulating inflammation response in HK-2 cells through SIRT1/NF-κB (p65) pathway. Consequently, M1, 6b, and 6d could be promising drug candidates for SIRT1 related diseases.

Conversion of β‐Nitrostyrenes to Naphthofurans via a Cascade Reaction with α‐ and β‐Naphthols

AbstractA safe and straightforward method has been developed for the synthesis of various naphthofurans derivatives from readily available α,β‐unsaturated nitroalkenes and naphthols in ChCl/ZnCl2 DES media via a cascade reaction. The employed methodology is solvent‐free, and ChCl/ZnCl2 DES is applied with the reaction media and catalyst dual roles. Via this reaction, 13 different naphthofuran derivatives, starting from both α‐ ad β‐naphthols have been prepared at 60 °C in 4 h with 86–94 % yields.

Gas-phase pyrolysis of benzo- and naphthofuran derivatives

Benzo- and naphthofuran carboxylates 1, 2 and carboxamides 3, 4 were synthesized and pyrolysed by flash vacuum pyrolysis at 550 and 650 °C/10−2 mmHg. 2-Formylbenzonitrile 7 from benzofurans and 2-formylnaphthonitrile 14 from naphthofurans were isolated and identified as major products. The mechanism suggested for these pyrolytic reactions involves elimination of alcohol and amine from carboxylates 1, 2 and carboxamides 3, 4 respectively, followed by extrusion of CO to form phenoxy and naphthoxycarbenes that leads to 7 and 14 respectively.

Isolation of Natural Naphthoquinones from Juglans regia and In Vitro Antioxidant and Cytotoxic Studies of Naphthoquinones and the Synthetic Naphthofuran Derivatives

The naphthoquinones and their derivatives containing hydroxyl group exhibit wide range of pharmacological activities, such as antioxidant, antibacterial, antiviral, anticancer, antimalarial, and antifungal activities. In particular, the antioxidant and anticancer behaviors of these compounds continue to draw attention of researchers. In the present communication, three natural naphthoquinones—juglone, lawsone, and plumbagin—isolated from the chloroform extract of nutshells of Juglans regia Linn. and two 1,4-naphthoquinone derivatives—ethyl-5-hydroxynaphtho[ 1,2-b]furan-3-carboxylate and diethylnaphtho[1,2-b:4,3-b′]difuran-3,4-dicarboxylate—and three 5-hydroxy- 1,4-naphthoquinone derivatives—diethyl-7-hydroxynaphtho[1,2-b:4,3-b']difuran-3,4-dicarboxylate,4-ethoxycarbonyl- 7-hydroxynaphtho[1,2-b:4,3-b']difuran-3-carboxylic acid, and 7-hydroxynaphtho[1,2-b:4,3-b']difuran-3,4- dicarboxylic acid were synthesized and examined for their in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) bioassays. In addition, the cytotoxicity test using human hepatocellular liver carcinoma cell line (HepG2) was carried out for all the compounds. The 5-hydroxy-1,4-naphthoquinone derivatives displayed almost equivalent scavenging activity in DPPH assay and higher activity in ABTS assay relative to ascorbic acid. On the other hand, naphthoquinones Juglone and Plumbagin showed lesser antioxidant activity, but higher cytotoxic activity than naphthofurans except for diethyl naphtho[1,2-b:4,3-b′]difuran-3,4-dicarboxylate, which showed excellent cytotoxic activity.

Docking, molecular dynamics, binding energy-MM-PBSA studies of naphthofuran derivatives to identify potential dual inhibitors against BACE-1 and GSK-3β

BACE-1 and GSK-3β both are potential therapeutic drug targets for Alzheimer’s disease. Recently, both these targets received attention for designing dual inhibitors. Till now only two scaffolds (triazinone and curcumin) derivatives have been reported as BACE-1 and GSK-3β dual inhibitors. In our previous work, we have reported first in class dual inhibitor for BACE-1 and GSK-3β. In this study, we have explored other naphthofuran derivatives for their potential to inhibit BACE-1 and GSK-3β through docking, molecular dynamics, binding energy (MM-PBSA). These computational methods were performed to estimate the binding affinity of naphthofuran derivatives towards the BACE-1 and GSK-3β. In the docking results, two derivatives (NS7 and NS9) showed better binding affinity as compared to previously reported inhibitors. Hydrogen bond occupancy of NS7 and NS9 generated from MD trajectories showed good interaction with the flap residues Gln73, Thr72 of BACE-1 and Arg141, Thr138 residues of GSK-3β. MM-PBSA and energy decomposition per residue revealed different components of binding energy and relative importance of amino acid involved in binding. The results showed that the binding of inhibitors was majorly governed by the hydrophobic interactions and suggesting that hydrophobic interactions might be the key to design dual inhibitors for BACE1-1 and GSK-3β. Distance between important pair of amino acid residues indicated that BACE-1 and GSK-3β adopt closed conformation and become inactive after ligand binding. The results suggested that naphthofuran derivatives might act as dual inhibitor against BACE-1 and GSK-3β.

Synthesis, in vitro Antibacterial and Cytotoxic studies of novel Naphthofurans

A simple, convenient and reproducible naphthofuran derivatives (1-5) were synthesized from 1,4-naphthoquinones and characterized by 1 H-NMR, 13 C-NMR, FT-IR, and Mass spectral studies. All the newly synthesized compounds were evaluated for in vitro antibacterial activity against Staphylococcus aureus (ATCC 6538) , Staphylococcus epidermidis (ATCC 155) and Bacillus cereus (ATCC 11778) as Gram positive bacteria; Escherichia coli (ATCC 25922) , Klebsiella pneumonia (ATCC 29665) and Pseudomonas aeruginosa (ATCC 25619) as Gram negative bacteria and their minimal inhibitory concentrations were determined. Amongst the tested organisms, compound 1 was the most active compound against all the tested organisms. All the compounds were evaluated for in vitro cytotoxicity potential using the standard MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against human cervical cancer cell line (HeLa) and compound 3 showed more potent than other compounds.

A Novel Approach to the Synthesis of Some Naphthofuran Derivatives Bearing Polar Substituents for Studying their Antimicrobial Activity

A Novel Approach to the Synthesis of Some Naphthofuran Derivatives Bearing Polar Substituents for Studying their Antimicrobial Activity

ChemInform Abstract: A Simple and Efficient Access to Naphtho[b]furans by Claisen Rearrangement/Cyclization of Bromonaphthyl 3‐Phenylallyl Ethers.

AbstractA transition‐metal‐free Claisen rearrangement/cyclization reaction is presented for the synthesis of naphthofuran derivatives from bromonaphthyl 3‐arylallyl ethers.

Facile synthesis of benzoindoles and naphthofurans through carbonaceous material-catalyzed cyclization of naphthylamines/naphthols with nitroolefins in water.

A facile and efficient approach has been established for the synthesis of benzoindole and naphthofuran derivatives via the metal-free cyclization reaction of nitroolefins with naphthylamines/naphthols. Various substituted benzoindoles and naphthofurans are obtained in good to excellent yields. Moreover, the ability to recycle the carbonaceous material makes this method quite cost-effective and environmentally benign compared to traditional acid-catalyzed methods. Theoretical studies indicated that the reaction between naphthylamine and nitroolefin catalyzed by this solid acid was thermodynamically controlled at 60 °C, resulting in the formation of the benzoindoles.

ChemInform Abstract: Synthesis and Properties of Butterfly‐Shaped Expanded Naphthofuran Derivatives.

The construction of dinaphtho[2,1-b;2′,3′-d]furan-6-ol was developed via a dehydration reaction involving two molecules of 2,3-dihydroxynaphthalene in the presence of a strong acid. Starting from the dinaphthofuran, a variety of butterfly shaped derivatives were synthesized. The optical properties of these compounds were investigated with special attention to the dihedral angle formed by adjacent dinaphthofuran rings and/or the sizes of the fused aromatic rings.

Synthesis and Properties of Butterfly-Shaped Expanded Naphthofuran Derivatives

The construction of dinaphtho[2,1-b;2',3'-d]furan-6-ol was developed via a dehydration reaction involving two molecules of 2,3-dihydroxynaphthalene in the presence of a strong acid. Starting from the dinaphthofuran, a variety of butterfly shaped derivatives were synthesized. The optical properties of these compounds were investigated with special attention to the dihedral angle formed by adjacent dinaphthofuran rings and/or the sizes of the fused aromatic rings.

In silico antitubercular activity analysis of benzofuran and naphthofuran derivatives.

For the human health, Mycobacterium tuberculosis (MTB) is the deadliest enemy since decades due to its multidrug resistant strains. During latent stage of tuberculosis infection, MTB consumes nitrate as the alternate mechanism of respiration in the absence of oxygen, thus increasing its survival and virulence. NarL is a nitrate/nitrite response transcriptional regulatory protein of two-component signal transduction system which regulates nitrate reductase and formate dehydrogenase for MTB adaptation to anaerobic condition. Phosphorylation by sensor kinase (NarX) is the primary mechanism behind the activation of NarL although many response regulators get activated by small molecule phospho-donors in the absence of sensor kinase. Using in silico approach, the molecular docking of benzofuran and naphthofuran derivatives and dynamic study of benzofuran derivative were performed. It was observed that compound Ethyl 5-bromo-3-ethoxycarbonylamino-1-benzofuran-2-carboxylate could be stabilized at the active site for over 10 ns of simulation. Here we suggest that derivatives of benzofuran moiety can lead to developing novel antituberculosis drugs.

Microwave-assisted Claisen rearrangement of naphthyl 2-propynyl ethers: synthesis of naphthofurans

An efficient two-step approach for the synthesis of naphtho[1,2-b]furans and naphtho[2,1-b]furans has been developed. Various functionalized propargyl alcohols were etherified with α- or β-naphthol under Mitsunobu reaction conditions to give naphthyl 2-propynyl ethers, which underwent a facile microwave-assisted Claisen rearrangement and concomitant anionic cyclization to yield naphthofuran derivatives under basic reaction conditions.

ChemInform Abstract: Direct Synthesis of Fused Indoles by Gold‐Catalyzed Cascade Cyclization of Diynes.

AbstractA new method to prepare diverse fused indoles as well as naphthofuran derivatives is reported.