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Cancer remains a leading cause of mortality worldwide, underscoring the urgent need for novel and effective therapeutic strategies. Naphthofurans, a class of heterocyclic compounds possessing a fused furan and naphthalene ring system, have emerged as promising candidates for anticancer drug development due to their diverse biological activities and structural versatility. This review provides an overview of recent advancements in the design, synthesis, and evaluation of naphthofuran derivatives as anticancer agents. We will examine the various mechanisms of action targeted by these compounds, including inhibition of enzymes, modulation of signaling pathways, induction of apoptosis, and disruption of the tumor microenvironment. Furthermore, we will highlight recent structure-activity relationship (SAR) studies, preclinical efficacy, and potential strategies for optimizing naphthofuran-based anticancer therapies.
Cancer is a complex disease characterized by uncontrolled cell growth and proliferation, leading to invasion and metastasis. Despite significant advancements in cancer treatment modalities such as surgery, radiation therapy, chemotherapy, and targeted therapies, the emergence of drug resistance and the presence of severe side effects remain major challenges. Therefore, the development of novel anticancer agents with improved efficacy and selectivity is crucial.
Heterocyclic compounds, particularly those containing nitrogen and oxygen atoms, play a vital role in medicinal chemistry, with a multitude of approved drugs based on these scaffolds. Naphthofurans, characterized by the fusion of a furan ring to a naphthalene moiety, represent an important class of heterocyclic compounds with diverse biological activities. Their relatively simple structure allows for readily modified substitutions, generating a wide range of derivatives with tailored properties.[1]
Increasing interest in naphthofuran has stemmed from their demonstrated anticancer potential, exhibiting activity against various cancer cell lines and animal models. This review focuses on recent developments in naphthofuran derivatives as anticancer agents, emphasizing their mechanisms of action, structure-activity relationships, and potential for further investigation as therapeutic candidates.
Heterocyclic compounds have a great importance in medicinal chemistry as they possess wide range of biological applications. Arylnaphthofurans are heterocyclic compounds consisting of fused ring system as aryl ring with furan moiety. Almost all natural naphthofuran such as (±)-laevigatin, (+)-heritol and balsaminonepossess potent pharmacological and cytotoxic properties. In recent past, due to its huge pharmacological potential and its interesting physiochemical properties it has drawn attention of lot of organic and medicinal chemist to develop convenient synthetic routes for their synthesis.[2]
NEWLY REPORTED NAPHTHOFURAN DERIVATIVES
Reported compound 1,2 and 3 show anticancer activity using MTT assay. Compound evaluated for in vitro cytotoxic activity against six human cancer cell lines PA1(ovary cancer cells), KB03(oral and mouth cancer cells), WRL68(liver cancer cells),COLO320DM(colon cancer cells), CaCO2(colon cancer cells) and MCF-7(hormone dependent breast cancer).[3]
Compound
Cancer cell lines
PA1
IC50
(µg/ml)
KB403
IC50
(µg/ml)
WRL68
IC50
(µg/ml)
COLO320DMIC50
(µg/ml)
CaCO2
IC50
(µg/ml)
MCF7
IC50
(µg/ml)
1
3.5
8.0
0.7
0.65
0.50
--------
2
4.0
-----
6.0
5.0
0.95
--------
3
-------
9.0
-----
------
------
--------
Reported compound (6) show anti proliferation, induction of DNA damage and apoptosis.
A series of 2-substituted 3-diethoxyphosphorylnaphtho [2,3-b] furan-4,9-diones are reported for their inhibitory potential against HL-60, NALM-6 and MCF-7 cell line. In this series compound 4,5,6 and 7 shown cytotoxic activity in table (2).[4]
The compound (6) shows significantly inhibit cell proliferation in MCF-7 cell line is observe in 34% and in HL-60 about 91% of cell population. Same potency observes the generation of DNA damage. Compound (6) is most potent against tested cell line HL-60, NALM-6 and MCF-7 IC50 values 6.35±0.46, 5.07±0.58 and 2.34±0.18µM respectively. Some reported naphthofuran derivatives show anti-proliferative activity in terms of LD50. From the MTT assay it was found that three compounds, Compounds 8, 9 and 10 showed significantly higher efficacy in blocking proliferation of MDA-MB-468 cells with LD50 values of (15 ± 3.1, 18 ± 1.2, 18 ± 2.4 µM respectively). Similar anti-proliferative efficacy of Compounds 8, 9 and 10are also found in the case of MCF-7 cells with LD50 values of (17 ± 2.65, 21 ± 3.9 and 19 ± 2.2 µM respectively).[5]
SYNTHESIS OF NAPHTHOFURAN DERIVATIVES
The synthesis of naphthofuran derivatives has been extensively investigated, and several efficient methodologies have been developed. General approaches typically involve the annulation of a furan ring onto a pre-existing naphthalene ring or the cyclization of an appropriately substituted naphthalene precursor to form the furan ring. Some commonly employed strategies include:
2-naphthol is reacted with basic chloroform in ethanol to yield 2-hydroxy-1-naphthaldehyde. Further 2-hydroxy-1-naphthaldehyde is reacted with ethyl 2-chloroacetate and K2CO3to yield naphtho[1,2-b]furan-2-carbohydrazide. Further ethyl-naphtho[2,1-b]furon-2-carboxylate, hydrazine hydrate in the presence of a catalytic quantity of conc. HCl in ethanol was refluxed at 30°C to get the naphtho[2,1-b]furan-2-carbohydrazide.[6,7]
Other method of synthesis of naphthofuran derivatives by base-catalyzed cyclization reaction of the corresponding o-alkoxybenzoylarene derivatives. The o-alkoxybenzoylarenesis obtained from the etherification reaction of the o-hydroxybenzoylarenes, which is prepare either by the reaction of methoxyarenes with benzoyl chloride in the presence of aluminum chloride or by photo-Fries rearrangement of aryl benzoates.[8]
An efficient and direct synthesis of naphtho[1,2 b]furans, naphtho[2,1-b]furans, and furo[3,2-c]chromenes is described. Heating a mixture of a naphthol or 4-hydroxycoumarin, an isocyanide, and an aldehyde under an argon atmosphere and sol vent-free conditions afforded the title compounds in excellent yields.[9]
Intramolecular Wittig Reaction: Allows for the formation of the furan ring through intramolecular olefination.[10]
Cyclization Reactions: Utilizing transition metal catalysts (e.g., palladium, copper) to promote cyclization reactions of substituted naphthalene derivatives.[11]
Cycloaddition Reactions: Diels-Alder reactions with furan analogs to construct the naphthofuran core.[12]
Microwave-Assisted Synthesis: Offers advantages such as shorter reaction times, higher yields, and cleaner reactions.[13]
Recent advancements have focused on developing more sustainable and efficient synthetic routes, including the use of biocatalysts and flow chemistry techniques. These methods offer the potential for large-scale production of naphthofuran derivatives with reduced environmental impact.
MECHANISMS OF ACTION OF NAPHTHOFURAN DERIVATIVES IN CANCER CELLS
Naphthofuran derivatives exhibit anticancer activity through various mechanisms of action, targeting different aspects of cancer cell survival, proliferation, and metastasis.[14]
Inhibition of Enzymes: Several naphthofurans have been shown to inhibit key enzymes involved in cancer progression, such as:
Topoisomerases: These enzymes are essential for DNA replication and repair. Inhibition of topoisomerases can lead to DNA damage and cell death.[15]
Kinases: Protein kinases play crucial roles in cell signaling pathways. Naphthofurans have been reported to inhibit kinases involved in cell proliferation, survival, and angiogenesis. (e.g., EGFR, VEGFR).[16]
Histone Deacetylases (HDACs): HDACs are involved in epigenetic regulation. Inhibiting HDACs can lead to chromatin remodeling and altered gene expression, resulting in cell cycle arrest and apoptosis.[17]
Modulation of Signaling Pathways: Naphthofurans can interfere with crucial signaling pathways that are often dysregulated in cancer cells, including:
NF-κB Pathway: This pathway is involved in inflammation, cell survival, and metastasis. Naphthofurans have been shown to inhibit the NF-κB pathway, leading to reduced expression of pro-inflammatory cytokines and anti-apoptotic proteins.[18]
PI3K/Akt/mTOR Pathway: This pathway regulates cell growth, proliferation, and metabolism. Naphthofurans can inhibit this pathway by targeting specific kinases, leading to cell cycle arrest and apoptosis.[19]
Wnt/β-catenin Pathway: This pathway is involved in embryonic development and tissue homeostasis. Aberrant activation of this pathway is found in various cancers. Naphthofurans can inhibit the Wnt/β-catenin pathway, disrupting cancer cell growth and proliferation.[20]
Induction of Apoptosis: Apoptosis, or programmed cell death, is a crucial mechanism for eliminating damaged or unwanted cells. Naphthofuran have been reported to induce apoptosis in cancer cells through various pathways, including:[21]
Mitochondrial Pathway: Naphthofuran can disrupt mitochondrial function, leading to the release of cytochrome c and activation of caspases, ultimately triggering apoptosis.
Death Receptor Pathway: Naphthofuran can activate death receptors on the cell surface, initiating a signaling cascade that leads to caspase activation and apoptosis.[22]
Disruption of the Tumor Microenvironment: The tumor microenvironment plays a critical role in cancer progression and metastasis. Naphthofuran have been shown to disrupt the tumor microenvironment by:
Inhibiting Angiogenesis: Blocking the formation of new blood vessels that supply nutrients to the tumor.[23]
Modulating Immune Cell Function: Influencing the activity of immune cells within the tumor microenvironment to promote an anti-tumor response.[24]
Inhibiting Metastasis: Preventing the spread of cancer cells to distant sites.[25]
STRUCTURE-ACTIVITY RELATIONSHIP (SAR) STUDIES
Understanding the SAR of naphthofuran derivatives is crucial for optimizing their anticancer activity. Researchers have explored the impact of various substituents at different positions on the naphthofuran scaffold to identify key structural features that contribute to enhanced potency and selectivity. Key findings from SAR studies include:
Substituents at C-2 and C-3 positions: Substitutions at these positions often influence the binding affinity of naphthofurans to target proteins, affecting their inhibitory activity. Bulky substituents can sometimes increase selectivity for certain targets.[26]
Amino and Alkyl Groups: The presence of amino or alkyl groups can enhance the solubility and bioavailability of naphthofurans, leading to improve in vivo efficacy.
Halogen Substituents: Halogen atoms (e.g., fluorine, chlorine) can increase the lipophilicity of naphthofurans, facilitating their penetration into cells and enhancing their interaction with hydrophobic binding pockets.
Linkers and Conjugates: Conjugating naphthofurans to other bioactive molecules or drug delivery systems can improve their targeted delivery to cancer cells and reduce off-target effects.[27]
PRECLINICAL EFFICACY AND IN VIVO STUDIES
Several naphthofuran derivatives have demonstrated promising anticancer activity in preclinical studies, exhibiting efficacy against various cancer cell lines and animal models. These studies have shown that naphthofurans can inhibit tumor growth, reduce metastasis, and prolong survival in vivo.
Specific examples of naphthofurans with in vivo efficacy against different cancer types are often presented in research publications and patents. Providing concrete examples is crucial for illustrating the potential of this class of compounds.[28]
CHALLENGES AND FUTURE DIRECTIONS
While naphthofuran derivatives hold great promise as anticancer agents, some challenges need to be addressed to facilitate their clinical translation.
Solubility and Bioavailability: Many naphthofurans exhibit poor solubility and bioavailability, limiting their in vivo efficacy. Strategies such as prodrug design, nanoparticle encapsulation, and formulation optimization can be employed to improve their pharmacokinetic properties.
Selectivity and Toxicity: Further research is needed to improve the selectivity of naphthofurans for cancer cells and reduce off-target toxicity. SAR studies and molecular modeling can help identify structural features that enhance selectivity for target proteins while minimizing interactions with other cellular components.
Drug Resistance: Cancer cells can develop resistance to naphthofurans through various mechanisms. Investigating the mechanisms of resistance and developing combination therapies that overcome resistance are crucial for improving the long-term efficacy of naphthofuran-based treatments.
Future research should focus on:
Developing more potent and selective naphthofuran derivatives through rational drug design and SAR studies.
Investigating the mechanisms of action of naphthofurans in greater detail to identify novel therapeutic targets.
Conducting preclinical studies to evaluate the efficacy and safety of naphthofurans in relevant animal models.
Exploring the potential of naphthofurans in combination with other anticancer therapies.
Developing innovative drug delivery systems to improve the targeted delivery of naphthofurans to cancer cells.
CONCLUSION
Naphthofuran derivatives represent a promising class of anticancer agents with diverse mechanisms of action and the potential to overcome some of the limitations of current cancer therapies. Recent advancements in the synthesis, SAR, and preclinical evaluation of these compounds have paved the way for further investigation as therapeutic candidates. By addressing the challenges of solubility, selectivity, and drug resistance, and by exploring innovative strategies for targeted delivery, naphthofuran-based therapies hold the potential to improve the outcomes for patients with cancer.
CONFLICT OF INTEREST
The authors have no conflicts of interest.
REFERENCES
Bohlmann F, Zdero C. Natürlich Vorkommende Terpen?Derivat. EinigeInhaltsstoffe Der GattungChromolaena.ChemischeBerichte. 1977;110:487-490.
Miles DH, Lho DS, De La Cruz AA, Gomez ED, Weeks JA, Atwood JL. Toxicants From Mangrove Plant. 3. Heritol, A Novel Ichthyotoxin FromThe Mangrove Plant Heritiera littoralis. The Journal Of Organic Chemistry. 1987 ;52:2930-2932.
Srivastava, V., Negi, A. S., Kumar, J. K., Faridi, U., Sisodia, B. S., Darokar, M. P., ... & Khanuja, S. P. S. (2006). Synthesis of 1-(3′, 4′, 5′-trimethoxy) phenyl naphtho [2, 1b] furan as a novel anticancer agent. Bioorganic & medicinal chemistry letters, 16(4), 911-914.
Gach, K., Modranka, J., Szyma?ski, J., Pomorska, D., Krajewska, U., Mirowski, M., ... & Janecka, A. (2016). Anticancer properties of new synthetic hybrid molecules combining naphtho [2, 3-b] furan-4, 9-dione or benzo [f] indole-4, 9-dione motif with phosphonate subunit. European journal of medicinal chemistry, 120, 51-63.
Star?evi?, K., Kralj, M., Piantanida, I., Šuman, L., Paveli?, K., &Karminski-Zamola, G. (2006). Synthesis, photochemical synthesis, DNA binding and antitumor evaluation of novel cyano-and amidino-substituted derivatives of naphtho-furans, naphtho-thiophenes, thieno-benzofurans, benzo-dithiophenes and their acyclic precursors. European journal of medicinal chemistry, 41(8), 925-939.
Kwon, S. M., Jung, Y. Y., Hwang, C. J., Park, M. H., Yoon, N. Y., Kim, T. M., ... & Hong, J. T. (2016). Anti?cancer effect of N?(3, 5?bis (trifluoromethyl) phenyl)?5?chloro?2, 3?dihydronaphtho [1, 2?b] furan?2?carboxamide, a novel synthetic compound. Molecular Carcinogenesis, 55(5), 659-670.
Islam, K., Pal, K., Debnath, U., Basha, R. S., Khan, A. T., Jana, K., & Misra, A. K. (2020). Anti-cancer potential of (1, 2-dihydronaphtho [2, 1-b] furan-2-yl) methanone derivatives. Bioorganic & Medicinal Chemistry Letters, 30(20), 127476.
Kumar, A., Srivastava, G., Negi, A. S., & Sharma, A. (2019). Docking, molecular dynamics, binding energy-MM-PBSA studies of naphthofuran derivatives to identify potential dual inhibitors against BACE-1 and GSK-3β. Journal of Biomolecular Structure and Dynamics, 37(2), 275-290.
Napiórkowska, M., Cie?lak, M., Ka?mierczak-Bara?ska, J., Królewska-Goli?ska, K., & Nawrot, B. (2019). Synthesis of new derivatives of benzofuran as potential anticancer agents. Molecules, 24(8), 1529.
Hranjec, M., Star?evi?, K., Piantanida, I., Kralj, M., Marjanovi?, M., Hasani, M., ... &Karminski-Zamola, G. (2008). Synthesis, antitumor evaluation and DNA binding studies of novel amidino-benzimidazolyl substituted derivatives of furyl-phenyl-and thienyl-phenyl-acrylates, naphthofurans and naphthothiophenes. European journal of medicinal chemistry, 43(12), 2877-2890.
Raghavendra, S. M., Kumaraswamy, M. N., Nagarsha, K. M., Sharanakumar, T. M., Ramamurthy, P. C., & Latha, K. P. (2023). Design, Synthesis, Molecular Docking, And Antimicrobial Study On Naphthofuran Derivatives. Rasayan Journal of Chemistry, 16(3), 1613-1623.
Badr, M. Z., El-Dean, A. M. K., Moustafa, O. S., & Zaki, R. M. (2006). Synthesis and biological study of some new naphtho [2, 1-b] furan and related heterocyclic systems. Journal of Chemical Research, 2006(11), 748-752.
Park, K. K., & Jeong, J. (2005). Facile synthesis of regio-isomeric naphthofurans and benzodifurans. Tetrahedron, 61(3), 545-553.
Adib, M., Mahdavi, M., Bagherzadeh, S., &Bijanzadeh, H. R. (2009). An efficient and direct solvent-free synthesis of naphtho [1, 2-b] furans, naphtho [2, 1-b] furans, and furo [3, 2-c] chromenes. Synlett, 2009(15), 2542-2544.
Tseng, C. H., Lin, C. S., Shih, P. K., Tsao, L. T., Wang, J. P., Cheng, C. M., ... & Chen, Y. L. (2009). Furo [3′, 2′: 3, 4] naphtho [1, 2-d] imidazole derivatives as potential inhibitors of inflammatory factors in sepsis. Bioorganic & medicinal chemistry, 17(18), 6773-6779.
Le Guével, R., Oger, F., Lecorgne, A., Dudasova, Z., Chevance, S., Bondon, A., ... &Salbert, G. (2009). Identification of small molecule regulators of the nuclear receptor HNF4α based on naphthofuran scaffolds. Bioorganic & medicinal chemistry, 17(19), 7021-7030.
Iqbal, J., Ejaz, S. A., Khan, I., Ausekle, E., Miliutina, M., & Langer, P. (2019). Exploration of quinolone and quinoline derivatives as potential anticancer agents. DARU Journal of Pharmaceutical Sciences, 27, 613-626.
Becker, K. B. (1980). Cycloalkenes by intramolecular Wittig reaction. Tetrahedron, 36(12), 1717-1745.
Ma, S. (2009). Electrophilic addition and cyclization reactions of allenes. Accounts of chemical research, 42(10), 1679-1688.
Nüchter, M., Ondruschka, B., Bonrath, W., & Gum, A. (2004). Microwave assisted synthesis–a critical technology overview. Green chemistry, 6(3), 128-141.
Kim, H. J., & Bae, S. C. (2010). Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. American journal of translational research, 3(2), 166.
Rhee, H. K., Park, H. J., Lee, S. K., Lee, C. O., & Choo, H. Y. P. (2007). Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of benzofuroquinolinediones. Bioorganic & medicinal chemistry, 15(4), 1651-1658.
El?Sayed, N. F., El?Hussieny, M., Ewies, E. F., El Shehry, M. F., Awad, H. M., & Fouad, M. A. (2022). Design, synthesis, biological evaluation, and molecular docking of new benzofuran and indole derivatives as tubulin polymerization inhibitors. Drug Development Research, 83(2), 485-500.
R Prosperi, J., & H Goss, K. (2010). A Wnt-ow of opportunity: targeting the Wnt/β-catenin pathway in breast cancer. Current drug targets, 11(9), 1074-1088.
O'Dea, E., & Hoffmann, A. (2009). NF?κB signaling. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 1(1), 107-115.
Moses, M. A., & Langer, R. (1991). Inhibitors of angiogenesis. Bio/technology, 9(7), 630-634.
Sweeney, B., Puri, P., & Reen, D. J. (2005). Modulation of immune cell function by polyunsaturated fatty acids. Pediatric surgery international, 21, 335-340.
Xie, K., Dong, Z., & Fidler, I. J. (1996). Activation of nitric oxide synthase gene for inhibition of cancer metastasis. Journal of leukocyte biology, 59(6), 797-803.
Reference
Bohlmann F, Zdero C. Natürlich Vorkommende Terpen?Derivat. EinigeInhaltsstoffe Der GattungChromolaena.ChemischeBerichte. 1977;110:487-490.
Miles DH, Lho DS, De La Cruz AA, Gomez ED, Weeks JA, Atwood JL. Toxicants From Mangrove Plant. 3. Heritol, A Novel Ichthyotoxin FromThe Mangrove Plant Heritiera littoralis. The Journal Of Organic Chemistry. 1987 ;52:2930-2932.
Srivastava, V., Negi, A. S., Kumar, J. K., Faridi, U., Sisodia, B. S., Darokar, M. P., ... & Khanuja, S. P. S. (2006). Synthesis of 1-(3′, 4′, 5′-trimethoxy) phenyl naphtho [2, 1b] furan as a novel anticancer agent. Bioorganic & medicinal chemistry letters, 16(4), 911-914.
Gach, K., Modranka, J., Szyma?ski, J., Pomorska, D., Krajewska, U., Mirowski, M., ... & Janecka, A. (2016). Anticancer properties of new synthetic hybrid molecules combining naphtho [2, 3-b] furan-4, 9-dione or benzo [f] indole-4, 9-dione motif with phosphonate subunit. European journal of medicinal chemistry, 120, 51-63.
Star?evi?, K., Kralj, M., Piantanida, I., Šuman, L., Paveli?, K., &Karminski-Zamola, G. (2006). Synthesis, photochemical synthesis, DNA binding and antitumor evaluation of novel cyano-and amidino-substituted derivatives of naphtho-furans, naphtho-thiophenes, thieno-benzofurans, benzo-dithiophenes and their acyclic precursors. European journal of medicinal chemistry, 41(8), 925-939.
Kwon, S. M., Jung, Y. Y., Hwang, C. J., Park, M. H., Yoon, N. Y., Kim, T. M., ... & Hong, J. T. (2016). Anti?cancer effect of N?(3, 5?bis (trifluoromethyl) phenyl)?5?chloro?2, 3?dihydronaphtho [1, 2?b] furan?2?carboxamide, a novel synthetic compound. Molecular Carcinogenesis, 55(5), 659-670.
Islam, K., Pal, K., Debnath, U., Basha, R. S., Khan, A. T., Jana, K., & Misra, A. K. (2020). Anti-cancer potential of (1, 2-dihydronaphtho [2, 1-b] furan-2-yl) methanone derivatives. Bioorganic & Medicinal Chemistry Letters, 30(20), 127476.
Kumar, A., Srivastava, G., Negi, A. S., & Sharma, A. (2019). Docking, molecular dynamics, binding energy-MM-PBSA studies of naphthofuran derivatives to identify potential dual inhibitors against BACE-1 and GSK-3β. Journal of Biomolecular Structure and Dynamics, 37(2), 275-290.
Napiórkowska, M., Cie?lak, M., Ka?mierczak-Bara?ska, J., Królewska-Goli?ska, K., & Nawrot, B. (2019). Synthesis of new derivatives of benzofuran as potential anticancer agents. Molecules, 24(8), 1529.
Hranjec, M., Star?evi?, K., Piantanida, I., Kralj, M., Marjanovi?, M., Hasani, M., ... &Karminski-Zamola, G. (2008). Synthesis, antitumor evaluation and DNA binding studies of novel amidino-benzimidazolyl substituted derivatives of furyl-phenyl-and thienyl-phenyl-acrylates, naphthofurans and naphthothiophenes. European journal of medicinal chemistry, 43(12), 2877-2890.
Raghavendra, S. M., Kumaraswamy, M. N., Nagarsha, K. M., Sharanakumar, T. M., Ramamurthy, P. C., & Latha, K. P. (2023). Design, Synthesis, Molecular Docking, And Antimicrobial Study On Naphthofuran Derivatives. Rasayan Journal of Chemistry, 16(3), 1613-1623.
Badr, M. Z., El-Dean, A. M. K., Moustafa, O. S., & Zaki, R. M. (2006). Synthesis and biological study of some new naphtho [2, 1-b] furan and related heterocyclic systems. Journal of Chemical Research, 2006(11), 748-752.
Park, K. K., & Jeong, J. (2005). Facile synthesis of regio-isomeric naphthofurans and benzodifurans. Tetrahedron, 61(3), 545-553.
Adib, M., Mahdavi, M., Bagherzadeh, S., &Bijanzadeh, H. R. (2009). An efficient and direct solvent-free synthesis of naphtho [1, 2-b] furans, naphtho [2, 1-b] furans, and furo [3, 2-c] chromenes. Synlett, 2009(15), 2542-2544.
Tseng, C. H., Lin, C. S., Shih, P. K., Tsao, L. T., Wang, J. P., Cheng, C. M., ... & Chen, Y. L. (2009). Furo [3′, 2′: 3, 4] naphtho [1, 2-d] imidazole derivatives as potential inhibitors of inflammatory factors in sepsis. Bioorganic & medicinal chemistry, 17(18), 6773-6779.
Le Guével, R., Oger, F., Lecorgne, A., Dudasova, Z., Chevance, S., Bondon, A., ... &Salbert, G. (2009). Identification of small molecule regulators of the nuclear receptor HNF4α based on naphthofuran scaffolds. Bioorganic & medicinal chemistry, 17(19), 7021-7030.
Iqbal, J., Ejaz, S. A., Khan, I., Ausekle, E., Miliutina, M., & Langer, P. (2019). Exploration of quinolone and quinoline derivatives as potential anticancer agents. DARU Journal of Pharmaceutical Sciences, 27, 613-626.
Becker, K. B. (1980). Cycloalkenes by intramolecular Wittig reaction. Tetrahedron, 36(12), 1717-1745.
Ma, S. (2009). Electrophilic addition and cyclization reactions of allenes. Accounts of chemical research, 42(10), 1679-1688.
Nüchter, M., Ondruschka, B., Bonrath, W., & Gum, A. (2004). Microwave assisted synthesis–a critical technology overview. Green chemistry, 6(3), 128-141.
Kim, H. J., & Bae, S. C. (2010). Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. American journal of translational research, 3(2), 166.
Rhee, H. K., Park, H. J., Lee, S. K., Lee, C. O., & Choo, H. Y. P. (2007). Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of benzofuroquinolinediones. Bioorganic & medicinal chemistry, 15(4), 1651-1658.
El?Sayed, N. F., El?Hussieny, M., Ewies, E. F., El Shehry, M. F., Awad, H. M., & Fouad, M. A. (2022). Design, synthesis, biological evaluation, and molecular docking of new benzofuran and indole derivatives as tubulin polymerization inhibitors. Drug Development Research, 83(2), 485-500.
R Prosperi, J., & H Goss, K. (2010). A Wnt-ow of opportunity: targeting the Wnt/β-catenin pathway in breast cancer. Current drug targets, 11(9), 1074-1088.
O'Dea, E., & Hoffmann, A. (2009). NF?κB signaling. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 1(1), 107-115.
Moses, M. A., & Langer, R. (1991). Inhibitors of angiogenesis. Bio/technology, 9(7), 630-634.
Sweeney, B., Puri, P., & Reen, D. J. (2005). Modulation of immune cell function by polyunsaturated fatty acids. Pediatric surgery international, 21, 335-340.
Xie, K., Dong, Z., & Fidler, I. J. (1996). Activation of nitric oxide synthase gene for inhibition of cancer metastasis. Journal of leukocyte biology, 59(6), 797-803.
Mohd Ateek
Corresponding author
Goel Institute of Pharmacy And Sciences, Anora kala, Lucknow (226010)
Goel Institute of Pharmacy and Sciences, Anora Kala, Lucknow, UP 266028.
Mohd Ateek*, Shahnawaz Ahmad, Recent Advancements in Naphthofuran Derivatives as Anti-Cancer Agents, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 6, 1254-1262. https://doi.org/10.5281/zenodo.15609629
10.5281/zenodo.15609629
