Engineered Artesunate-Naphthalimide Hybrid Dual Drug for Synergistic Multimodal Therapy against Experimental Murine Lymphoma.

Lymphoma can effectively be treated with a chemotherapy regimen that is associated with adverse side effects due to increasing drug resistance, so there is an emergent need for alternative small-molecule inhibitors to overcome the resistance that occurs in lymphoma management and overall increase the prognosis rate. A new series of substituted naphthalimide moieties conjugated via ester and amide linkages with artesunate were designed, synthesized, and characterized. In addition to the conjugates, to further achieve a theranostic molecule, FITC was incorporated via a multistep synthesis process. DNA binding studies of these selected derivatives by ultraviolet-visible (UV-vis), fluorescence spectroscopy, intercalating dye (EtBr, acridine orange)-DNA competitive assay, and minor groove binding dye Hoechst 33342-DNA competitive assay suggested that the synthesized novel molecules intercalated between the two strands of DNA due to its naphthalimide moiety and its counterpart artesunate binds with the minor groove of DNA. Napthalimide-artesunate conjugates inhibit the growth of lymphoma and induce apoptosis, including ready incorporation and reduction in cell viability. The remodeled drug has a significant tumoricidal effect against solid DL tumors developed in BALB/c mice in a dose-dependent manner. The novel drug appears to inhibit metastasis and increase the survival of the treated animals compared with untreated littermates.

Research Progress on Structure-Activity Relationship of 1,8-Naphthalimide DNA Chimeras Against Tumor.

The development of 1,8-naphthalimide derivatives as cell probes, DNA targeting agents, and anti-tumor drugs is one of the research hotspots in the field of medicine. Naphthalimide compounds are a kind of DNA embedder, which can change the topological structure of DNA by embedding in the middle of DNA base pairs, and then affect the recognition and action of topoisomerase on DNA. Aminofide and mitonafide are the first 2 drugs to undergo clinical trials. They have good DNA insertion ability, can embed DNA double-stranded structure, and induce topoisomerase II to cut part of pBR322DNA, but not yet entered the market due to their toxicity. In this paper, the design and structure-activity relationship of mononaphthalimide and bisaphthalimide compounds were studied, and the relationship between the structure of naphthalimide and anti-tumor activity was analyzed and discussed. It was found that a variety of structural modifications were significant in improving anti-tumor activity and reducing toxicity.

An Outlook of the Structure Activity Relationship (SAR) of Naphthalimide Derivatives as Anticancer Agents.

The efficacy of drugs against cancer in clinical settings may be limited due to pharmacokinetic issues, side effects and the emergence of drug resistance. However, a class of anticancer drugs known as naphthalimides have proven to be very effective. These derivatives have demonstrated to be effective in treating different types of cancers and exhibit strong DNA binding affinity. The anticancer properties of the naphthalimide derivatives allow them to target a number of cancer cell lines. Researchers have investigated the anticancer activity of numerous naphthalimide derivatives, such as heterocyclic fused, non-fused substituted, metal-substituted and carboxamide derivatives. Surprisingly, some derivatives demonstrate greater activity than the reference norms, such as cisplatin, amonafide, mitonafide and others and are selective against many cell lines. The primary objective of this research is to comprehend the effects of various substitution patterns on the structure-activity relationship (SAR) of these derivatives and the instances in which they enhance or reduce this biological activity.

Spectroscopic and Biological Properties of the 3-Imino-1,8-naphthalimide Derivatives as Fluorophores for Cellular Imaging.

This paper presents the photophysical and biological properties of eight 3-imino-1,8-naphthalimides. The optical properties of the compounds were investigated in the solvents that differed in their polarity (dichloromethane, acetonitrile, and methanol), including three methods of sample preparation using different pre-dissolving solvents such as dimethyl sulfoxide or chloroform. In the course of the research, it was found that there are strong interactions between the tested compounds and DMSO, which was visible as a change in the maximum emission band (λem) of the neat 3-imino-1,8-naphthalimides (λem = 470-480 nm) and between the compounds and DMSO (λem = 504-514 nm). The shift of the emission maximum that was associated with the presence of a small amount of DMSO in the sample was as much as 41 nm. In addition, the susceptibility of imines to hydrolysis in the methanol/water mixture with increasing water content and in the methanol/water mixture (v/v; 1:1) in the pH range from 1 to 12 was discussed. The studies showed that the compounds are hydrolysed in the CH3OH/H2O system in an acidic environment (pH in the range of 1 to 4). In addition, it was found that partial hydrolysis occurs in systems with an increased amount of water, and its degree may depend on the type of substituent on the imine bond. The compounds tended to quench the emission (ACQ) in the aggregated state and increase the emission related to the protonation of the imine bond. Moreover, it was found that the substituent in the imine bonds influenced a compound's individual photophysical properties. Biological tests, including cytotoxicity studies and cellular localisation, were also performed for all of the molecules. All of the tested compounds exhibited green fluorescence in the MCF-7 cells and showed co-localisation in the mitochondria, endoplasmic reticulum, and lysosome. The obtained photophysical and biological results indicate the promising potential use of the tested compounds as cellular dyes.

An ICT-FRET-based ratiometric fluorescent probe for hydrogen polysulfide based on a coumarin-naphthalimide derivative.

Hydrogen polysulfide (H2Sn, n > 1), as one of the important members of reactive sulfur species (RSS), plays a vital part in the processes of both their physiology and pathology. In this work, a ratiometric fluorescent probe for H2Sn had been designed and prepared based on the combination mechanism of intramolecular charge transfer (ICT) and fluorescence resonance energy transfer (FRET). The probe chose a coumarin derivative as the energy donor, a naphthalimide derivative as the energy acceptor and 2-fluoro-5-nitrobenzoate as the H2Sn recognition group. When H2Sn was not present in the system, the ICT process of the naphthalimide acceptor was inhibited and the FRET process from the coumarin donor to the naphthalimide acceptor was turned off. When H2Sn was added, both ICT and FRET occurred due to the nucleophilic substitution-cyclization reactions between the probe and hydrogen polysulfide. In addition, the ratio value of the emission intensities at 550 nm and 473 nm (I550 nm/I473 nm) of this probe had a good linear relationship with H2Sn concentration in the range of 6.0 × 10-7-5.0 × 10-5 mol·L-1, and a detection limit of 1.8 × 10-7 mol·L-1 was obtained. The developed probe had high selectivity and sensitivity, as well as good biocompatibility. Additionally, the probe had been used to successfully image both indigenous and exogenous hydrogen polysulfide in A549 cells using confocal microscope.

Biocompatible 7-nitro-2,1,3-benzoxadiazole-embedded naphthalimide for exploring endogenous H2S in living cells.

Hydrogen sulfide (H2S) is a central signaling and antioxidant biomolecule involved in various biological processes. As inappropriate levels of H2S in the human body are closely related to various diseases, including cancer, a tool capable of detecting H2S with high selectivity and sensitivity in living systems is urgently required. In this work, we intended to develop a biocompatible and activatable fluorescent molecular probe for detecting H2S generation in living cells. The 7-nitro-2,1,3-benzoxadiazole-imbedded naphthalimide (1) probe presented here responds specifically to H2S and produces readily detectable fluorescence at 530 nm. Interestingly, probe 1 exhibited significant fluorescence responses to changes in endogenous H2S levels as well as high biocompatibility and permeability in living HeLa cells. This allowed for the real-time monitoring of endogenous H2S generation as an antioxidant defense response in the oxidatively stressed cells.

A bio-friendly biotin-coupled and azide-functionalized naphthalimide for real-time endogenous hydrogen sulfide analysis in living cells.

Hydrogen sulfide (H2S) is involved in various biological processes. Thereby, abnormal levels of H2S are reported to be related to various human diseases including cancer. Currently, many fluorescent probes are pioneered to detect H2S by taking advantages of naphthalimides' unique internal charge transfer (ICT) property. However, most probes often require a high content of organic solvents or surfactants, and are limited to the analysis of exogenous H2S treated externally in live cell studies, and have difficulties in analyzing endogenous H2S, thus limiting their practical use. In this study, we developed a bio-friendly biotin-coupled and azide-functionalized naphthalimide (1) as a fluorescent probe enabling real-time analysis of H2S in living system. Probe was able to provide a fluorescence at 545 nm via H2S-mediated azide reduction selectively without interference by biologically abundant constituents and pH effects. In a biological study using A549 cells, probe readily penetrated living cells without cytotoxicity, and unreacted probes showed almost no fluorescence, enabling real-time detection of H2S in living cells without requiring separate washing process. More importantly, under stimulation with various H2S inducers and inhibitors, probe was able to provide an effective fluorescence response against fluctuations in endogenous H2S, a key requirement for H2S studies. Probe 1 can be applied as a useful chemical tool and enables the analysis of H2S and the study of H2S-related cell functions in a variety of environments.

Fluorescence sensing and glycosidase inhibition effect of multivalent glycosidase inhibitors based on Naphthalimide-deoxynojirimycin conjugates.

Synthetic glycoconjugates as chemical probes have been widely developed for the detection of glycosidase enzymes. However, the binding interactions between iminosugar derivatives and glycosidases were limited, especially for the binding interactions between multivalent glycosidase inhibitors and α-glycosidases. In this paper, three naphthalimide-DNJ conjugates were synthesized. Furthermore, the binding interactions and glycosidase inhibition effects of them were investigated. It was found that the strong binding interactions of multivalent glycosidase inhibitors with enzymes were related to the efficient inhibitory activity against glycosidase. Moreover, the lengths of the chain between DNJ moieties and the triazole ring for the naphthalimide-DNJ conjugates influenced the self-assembly properties, binding interactions and glycosidase inhibition activities with multisource glycosidases. Compound 13 with six carbons between the DNJ moiety and triazole ring showed the stronger binding interactions and better glycosidase inhibition activities against α-mannosidase (jack bean) and α-glucosidase (aspergillus niger). In addition, compound 13 showed an effective PBG inhibition effect in mice with 51.18 % decrease in blood glucose at 30 min. This result opens a way for detection of multivalent glycosidase inhibition effect by a fluorescent sensing method.

Discovery and Characterization of Novel Naphthalimide Analogs as Potent Multitargeted Directed Ligands against Alzheimer's Disease.

Current therapeutic drugs for Alzheimer's disease (AD) can only offer limited symptomatic benefits and do not halt disease progression. Multitargeted directed ligands (MTDLs) have been considered to be a feasible way to treat AD due to the multiple neuropathological processes in AD. Previous studies proposed that compounds containing two aromatic groups connected by a carbon chain should act as effective amyloid ß (Aß) aggregation inhibitors although the optimal length of the carbon chain has not been explored. In the current study, a series of naphthalimide analogs were designed and synthesized based on the proposed structure and multiple bioactivities beneficial to the AD treatment were reported. In vitro studies showed that compound 8, which has two aromatic groups connected by a two-carbon chain, exhibited significant inhibition of Aß aggregation through the prevention of elongation and association of Aß fibril growth. Furthermore, this compound also displayed antioxidative activities and neuroprotection from Aß monomer induced toxicity in primary cortical neurons. The results of the present study highlight a novel naphthalimide-based compound 8 as a promising MTDL against AD. Its structural elements can be further explored for enhanced therapeutic capabilities.

Improving reactivity of naphthalimide-based GST probe by imparting TPP cation: Development and application for live cell imaging.

Glutathione S-transferases (GSTs) are a superfamily of multifunctional enzymes comprising multiple classes and subtypes. This paper describes the synthesis and characterization of TPPBN-1, a naphthalimide derivative conjugated with a triphenylphosphonium (TPP) cation. When 4-bromonaphthalimide (BrNaph), a previously characterized GST substrate, was conjugated to a TPP cation, the conjugate showed increased reactivity towards most alpha- and mu-class GSTs, particularly the GSTA2 subtype, compared to the parent compound, but hardly towards Pi-class GSTs. Using this probe with enhanced reactivity, the enzymatic activity of endogenous GSTA1/2 in HepG2 cells was visualized by confocal fluorescence microscopy. The results demonstrated that modification with TPP cations, which are often used as tags for targeting mitochondria, can be used to enhance the reactivity of probes for specific GST subtypes.

Identification of Novel Antifungal Skeleton of Hydroxyethyl Naphthalimides with Synergistic Potential for Chemical and Dynamic Treatments.

The invasion of pathogenic fungi poses nonnegligible threats to the human health and agricultural industry. This work exploited a family of hydroxyethyl naphthalimides as novel antifungal species with synergistic potential of chemical and dynamic treatment to combat the fungal resistance. These prepared naphthalimides showed better antifungal potency than fluconazole towards some tested fungi including Aspergillus fumigatus, Candida tropicalis and Candida parapsilosis 22019. Especially, thioether benzimidazole derivative 7f with excellent anti-Candida tropicalis efficacy (MIC = 4 µg/mL) possessed low cytotoxicity, safe hemolysis level and less susceptibility to induce resistance. Biochemical interactions displayed that 7f could form a supramolecular complex with DNA to block DNA replication, and constitute a biosupermolecule with cytochrome P450 reductase (CPR) from Candida tropicalis to hinder CPR biological function. Additionally, 7f presented strong lipase affinity, which facilitated its permeation into cell membrane. Moreover, 7f with dynamic antifungal potency promoted the production and accumulation of reactive oxygen species (ROS) in cells, which destroyed the antioxidant defence system, led to oxidative stress with lipid peroxidation, loss of glutathione, membrane dysfunction and metabolic inactivation, and eventually caused cell death. The chemical and dynamic antifungal synergistic effect initiated by hydroxyethyl naphthalimides was a reasonable treatment window for prospective development.

Design, Synthesis, and Herbicidal Activity of Naphthalimide-Aroyl Hybrids as Potent Transketolase Inhibitors.

Transketolase (TK) was identified as a new target for the development of novel herbicides. In this study, a series of naphthalimide-aroyl hybrids were designed and prepared based on TK as a new target and tested for their herbicidal activities. In vitro bioassay showed that compounds 4c and 4w exhibited stronger inhibitory effects against Digitaria sanguinalis (DS) and Amaranthus retroflexus (AR) with the inhibition over 90% at 200 mg/L and around 80% at 100 mg/L. Also, compounds 4c and 4w exhibited excellent postemergence herbicidal activity against DS and AR with the inhibition around 90% at 90 g [active ingredient (ai)]/ha and 80% at 50 g (ai)/ha in the greenhouse, which was comparable with the activity of mesotrione. The fluorescent quenching experiments of At TK revealed the occurrence of electron transfer from compound 4w to At TK and the formation of a strong exciplex between them. Molecular docking analyses further showed that compounds 4w exhibited profound affinity with At TK through the interaction with the amino acids in the active site, which results in its strong inhibitory activities against TK. These findings demonstrated that compound 4w is potentially a lead candidate for novel herbicides targeting TK.

Enhanced Photodynamic Efficacy Using 1,8-Naphthalimides: Potential Application in Antibacterial Photodynamic Therapy.

This study addresses the need for antibacterial medication that can overcome the current problems of antibiotics. It does so by suggesting two 1,8-naphthalimides (NI1 and NI2) containing a pyridinium nucleus become attached to the imide-nitrogen atom via a methylene spacer. Those fluorescent derivatives are covalently bonded to the surface of a chloroacetyl-chloride-modified cotton fabric. The iodometric method was used to study the generation of singlet oxygen (1O2) by irradiation of KI in the presence of monomeric 1,8-naphthalimides and the dyed textile material. Both compounds generated reactive singlet oxygen, and their activity was preserved even after they were deposited onto the cotton fabric. The antibacterial activity of NI1 and NI2 in solution and after their covalent bonding to the cotton fabric was investigated. In vitro tests were performed against the model gram-positive bacteria B. cereus and gram-negative P. aeruginosa bacteria in dark and under light iradiation. Compound NI2 showed higher antibacterial activity than compound NI1. The light irradiation enhanced the antimicrobial activity of the compounds, with a better effect achieved against B. cereus.

Theoretical study on a series of naphthalimide-contained two-photon fluorescent hypochlorite probe targeting endoplasmic reticulum: response mechanism and receptor effect.

The development of detecting hypochlorous acid (HClO) in living endoplasmic reticulum has attracted much attention in the fields of biology, medicine, and pharmacy. In the present work, the one-photon absorption (OPA), one-photon emission (OPE), and two-photon absorption (TPA) properties of a series newly synthesized chemosensors with naphthalimide as the fluorophore were systematically investigated using time-dependent density functional theory in combination with response theory. Special emphasis is placed on evolution of the probes' optical properties in the presence of HClO. These compounds show drastic changes in their photoabsorption and photoemission properties when they react with HClO, indicating them to be excellent candidates as fluorescent chemosensors. To further understand the mechanisms of the two probes, we have employed the hole and electron analysis to investigate the charge transfer process for the photoemission of the molecules. The receptor effect is found to play a dominant role in the sensing performance of these probes. Specifically, two-photon absorption properties of the molecules are calculated. We have found that all probes show significant two-photon responses in the near-infrared light region. And the maximum two-photon absorption cross section of probe 2 is greatly enhanced with the presence of HClO, indicating that probe 2 can act as a potential two-photon excited fluorescent HClO probe. The theoretical investigations would be helpful to build the structure-property relationships for the naphthalimide-contained probes, providing information on the design of efficient two-photon fluorescent sensors that can be used for biological imaging of HClO in endoplasmic reticulum.

Light Triggers the Antiproliferative Activity of Naphthalimide-Conjugated (η6-arene)ruthenium(II) Complexes.

We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η6-arene)Ru(N,N')L][PF6]2 containing arene = p-cymene, N,N' = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λmax = 418 nm) compared with C1 and C2 (λmax = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC50 = 10.55 ± 0.30 µM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT).

Utilising fluorescent reporters to probe the mode of action of norbornen-7-one CO releasing molecules.

The synthesis of the fluorescent organic carbon monoxide releasing molecules oCOm-57, oCOm-58, and oCOm-66 are reported. These oCOms are water soluble and exhibit a "turn-on" fluorescent behaviour when CO is released under physiological conditions. oCOm-66 also contains an additional nitro-naphthalimide moiety that functions as a fluorescent reporter. Delivery of CO released from these oCOms to the mitochondria of AC-16 cardiomyocytes was confirmed using confocal microscopy in conjuction with MitoTracker Red. While the neutral, PEGylated oCOm-57 was found to remain in the extracellular environment releasing CO to diffuse into the cellular compartments, the positively charged oCOm-58 and -66 are targeted to the mitochondria where they release CO. Notably, the use of the fluorescent oCOms in live cellular imaging, allows the intracellular CO delivery and oCOm localisation to be characterised. This cellular confocal study also shows that, subtoxic concentrations of CO released from these molecules preserved mitochondrial energetics as indicated by the membrane potential dependent MitoTracker Red.

Design, synthesis and anti-tumor activity of novel benzothiophenonaphthalimide derivatives targeting mitochondrial DNA (mtDNA) G-quadruplex.

A series of new naphthalimide derivatives, benzothiophenonaphthalimides (7a-7g, 8a-8g), were designed and synthesized, of which compounds 8a-8g are hydrochloride salts of corresponding compounds 7a-7g. All compounds presented different anti-tumor activities for tumor cells tested by the CCK-8 assay. In particular, compound 7c displayed the strongest anti-tumor activity with an IC50 value of 0.59 ± 0.08 µM and the best selectivity for HepG2 cells. At the same time, it was observed that 7c could induce HepG2 cell apoptosis, hinder cancer cell migration and arrest the cell cycle at the G2/M phase. Further mechanism studies revealed that 7c selectively induced a G-rich HRCC DNA sequence in the mitochondria to form a G-quadruplex structure (G4) and stabilized it, which mediated the decrease in mitochondrial membrane potential and the production of reactive oxygen species, causing mitochondrial dysfunction. Finally, this led to proliferative inhibition and apoptosis of cancer cells and protective autophagy by promoting the expression of p-Erk1/2. The in vivo experimental results indicated that the compound 8c as a salt of 7c showed significant in vivo anti-tumor efficacy in the HepG2-xenograft mouse model with a tumor growth inhibition rate of 51.4% at a dose of 15 mg/kg. These results suggest that 7c possesses a different anti-tumor mechanism from the previous main reported mechanism of naphthalimide derivatives, which targets the nucleus. In brief, 7c has good anti-tumor activity in vitro and in vivo and may act as a leading compound in development of drugs against liver cancer.

Platinum-Based Two-Photon Photosensitizer Responsive to NIR Light in Tumor Hypoxia Microenvironment.

Platinum-based photosensitizers are promising anticancer agents in photodynamic therapy. The cytotoxic effects primarily arise from the production of singlet oxygen and platination of DNA. However, their efficacy is limited by drug resistance and hypoxic tumor microenvironment. A naphthalimide-modified cyclometalated platinum(II) complex PtPAN [PA = N-(2-(diethylamino)ethyl)picolinamide, N = N-(2'-ethylhexyl)-4-ethynyl-1,8-naphthalimide] is designed to conquer these problems. PtPAN generates ROS efficiently under both normoxia and hypoxia. It does not interact with DNA and shows low cytotoxicity in the dark, while it kills tumor cells via ROS under near-infrared light irradiation; moreover, it inhibits tumor growth in mice at a low light dose with negligible side effects. PtPAN is the first reported platinum-based photosensitizer that is unreactive to DNA in the dark but highly cytotoxic upon near-infrared (NIR) irradiation for oxygen-independent photodynamic therapy. Owing to its two-photon excitation property (λ = 825 nm), PtPAN may be suitable for the treatment of deep solid tumors.

Design, synthesis and bioactivity of novel naphthalimide-benzotriazole conjugates against A549 cells via targeting BCL2 G-quadruplex and inducing autophagy.

AIMS: In this study, a series of novel naphthalimide-benzotriazole conjugates (1a-3c) based on 1, 8-naphthalimide as a core skeleton, aiming at G-quadruplexes, were designed and synthesized, and their anti-cancer activity and mechanism were studied. MATERIALS AND METHODS: Using the CCK-8 assay, FRET melting, EMSA, CD, and molecular docking, intracellular assays, western blotting, immunofluorescence, and flow cytometry. KEY FINDINGS: By the CCK-8 assay, it was found that the compound, 2-(3-(piperazin-1-yl)propyl)-6-(1H-benzo [d][1,2,3]triazol-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (3a), has better activity against A549 cells. Through extracellular assays, including FRET melting, EMSA, CD, and molecular docking, results showed that 3a selectively interacted with BCL2 G-quadruplex(es). Further studies by intracellular assays, including western blotting, immunofluorescence, flow cytometry, etc., verified that 3a mediated the death of A549 cells by two pathways: inhibition of the expression of the BCL2 gene, causing tumor cell apoptosis, and promotion of genetic instability, causing autophagy. This study suggests that the type of compounds, in particular, 3a, may be a potential molecule to explore for BCL2 G-quadruplex-targeted drugs against lung cancer. SIGNIFICANCE: Our findings demonstrate that compound 3a as a BCL2 G-quadruplex ligand induces DNA damage, autophagy, and apoptosis in A549 cells. This study provides us with a type of lead compound as an anti-tumor drug.

Recent developments on 1,8-Naphthalimide moiety as potential target for anticancer agents.

1,8-Naphthalimide moiety is well known to possess various biological activities as it can very well intercalate with DNA. In recent years, much of the attention has been given to the preparation of naphthalimide derivatives by substitution at various positions of the 1,8-naphthalimide ring for their exploration as anticancer agents. These derivatives possess different anticancer properties, which cover a broader range of cancer cell lines. Interestingly, some derivatives include enhanced activity than the reference standards like cisplatin, amonafide, mitonafide, etc., and be selective against the cell lines. The aim is to study the effect of different modulations at various positions of the 1,8-naphthalimide ring with a polyamine, thiourea, benzothiazole, benzimidazole, and formation of metal complexes and bis-naphthalimides that affects the overall cytotoxic properties of the resulting 1,8-naphthalimides. Moreover, the structure-activity relationship of these variations for the resulting derivatives' anticancer properties has also been discussed. Thus, this review will be important for a wide range of researchers to design and development of various 1,8-naphthalimide derivatives with desired drug profiles.