Design and Synthesis of Poly(2,2'-Bipyridyl) Ligands for Induction of Cell Death in Cancer Cells: Control of Anticancer Activity by Complexation/Decomplexation with Biorelevant Metal Cations.

Chelation therapy is a medical procedure for removing toxic metals from human organs and tissues and for the treatment of diseases by using metal-chelating agents. For example, iron chelation therapy is designed not only for the treatment of metal poisoning but also for some diseases that are induced by iron overload, cancer chemotherapy, and related diseases. However, the use of such metal chelators needs to be generally carried out very carefully, because of the side effects possibly due to the non-specific complexation with intracellular metal cations. Herein, we report on the preparation and characterization of some new poly(bpy) ligands (bpy: 2,2'-bipyridyl) that contain one-three bpy ligand moieties and their anticancer activity against Jurkat, MOLT-4, U937, HeLa S3, and A549 cell lines. The results of MTT assays revealed that the tris(bpy) and bis(bpy) ligands exhibit potent activity for inducing the cell death in cancer cells. Mechanistic studies suggest that the main pathway responsible for the cell death by these poly(bpy) ligands is apoptotic cell death. It was also found that the anticancer activity of the poly(bpy) ligands could be controlled by the complexation (anticancer activity is turned OFF) and decomplexation (anticancer activity is turned ON) with biorelevant metal cations. In this paper, these results will be described.

Post-complexation Functionalization of Cyclometalated Iridium(III) Complexes and Applications to Biomedical and Material Sciences.

Cyclometalated iridium(III) (Ir(III)) complexes exhibit excellent photophysical properties that include large Stokes shift, high emission quantum yields, and microsecond-order emission lifetimes, due to low-lying metal-to-ligand charge transfer (spin-forbidden singlet-triplet (3MLCT) transition). As a result, analogs have been applied for research not only in the material sciences, such as the development of organic light-emitting diodes (OLEDs), but also for photocatalysts, bioimaging probes, and anticancer reagents. Although a variety of methods for the synthesis and the applications of functionalized cyclometalated iridium complexes have been reported, functional groups are generally introduced to the ligands prior to the complexation with Ir salts. Therefore, it is difficult to introduce thermally unstable functional groups such as peptides and sugars due to the harsh reaction conditions such as the high temperatures used in the complexation with Ir salts. In this review, the functionalization of Ir complexes after the formation of cyclometalated Ir complexes and their biological and material applications are described. These methods are referred to as "post-complexation functionalization (PCF)." In this review, applications of PCF to the design and synthesis of Ir(III) complexes that exhibit blue -red and white color emissions, luminescence pH probes, luminescent probes of cancer cells, compounds that induce cell death in cancer cells, and luminescent complexes that have long emission lifetimes are summarized.

Cyclometalated Iridium(III) Complex-Cationic Peptide Hybrids Trigger Paraptosis in Cancer Cells via an Intracellular Ca2+ Overload from the Endoplasmic Reticulum and a Decrease in Mitochondrial Membrane Potential.

In our previous paper, we reported that amphiphilic Ir complex-peptide hybrids (IPHs) containing basic peptides such as KK(K)GG (K: lysine, G: glycine) (e.g., ASb-2) exhibited potent anticancer activity against Jurkat cells, with the dead cells showing a strong green emission. Our initial mechanistic studies of this cell death suggest that IPHs would bind to the calcium (Ca2+)-calmodulin (CaM) complex and induce an overload of intracellular Ca2+, resulting in the induction of non-apoptotic programmed cell death. In this work, we conduct a detailed mechanistic study of cell death induced by ASb-2, a typical example of IPHs, and describe how ASb-2 induces paraptotic programmed cell death in a manner similar to that of celastrol, a naturally occurring triterpenoid that is known to function as a paraptosis inducer in cancer cells. It is suggested that ASb-2 (50 µM) induces ER stress and decreases the mitochondrial membrane potential (ΔΨm), thus triggering intracellular signaling pathways and resulting in cytoplasmic vacuolization in Jurkat cells (which is a typical phenomenon of paraptosis), while the change in ΔΨm values is negligibly induced by celastrol and curcumin. Other experimental data imply that both ASb-2 and celastrol induce paraptotic cell death in Jurkat cells, but this induction occurs via different signaling pathways.

Rh(iii)-Catalysed synthesis of cinnolinium and fluoranthenium salts using C-H activation/annulation reactions: organelle specific mitochondrial staining applications.

The construction of a novel class of indazolo[2,1-a]cinnolin-7-ium and diazabenzofluoranthenium salts was developed by using Rh(iii)-catalyzed C-H activation/annulation reactions with 2-phenyl-2H-indazole, and internal alkynes, which resulted in structurally important polycyclic heteroaromatic compounds (PHAs). This reaction uses mild reaction conditions and has a high efficiency, low catalyst loading, and wide substrate scope. The overall catalytic process involves C-H activation followed by C-C/C-N bond formation. Furthermore, the synthesised cinnolinium/fluoranthenium salts exhibit potential fluorescence properties and 5i was targeted in particular for specific mitochondrial staining in order to investigate cancer cell lines.

Synthesis, characterization, theoretical, molecular docking and in vitro biological activity studies of Ru(II) (η6-p-cymene) complexes with novel aniline substituted aroyl selenoureas.

A sequence of aroyl selenourea ligands (L1-L3) substituted by aniline and their Ru(II) (η6-p-cymene) complexes (1-3), [Ru(II) (η6-p-cymene) L] (L = monodentate aroyl selenourea ligand) have been synthesized and characterized the composition of the ligands and their metal complexes. The molecular structures of ligand L1 and complex 3 were also confirmed by single XRD crystal method. The single-crystal XRD study showed that aroyl selenourea ligand coordinates with Ru via Se novel neutral monodentate atom. In vitro DNA interaction studies were investigated by Fluorescence and UV-Visible spectroscopic methods which showed that the intercalative mode of binding is in the order of 1 > 2 > 3 with Ru(II) (η6-p-cymene) complexes. Spectroscopic methods have been used for measuring the binding affinity of bovine serum albumin to complex. Moreover, the cytotoxic study of complexes (1-3) were evaluated against HeLa S3, A549, and IMR90 cells, resulting in complexes 1 and 2 showed promising cytotoxic activity against HeLa S3 cell with IC50 values of 24 and 26 µM, respectively. Also, the morphological changes of HeLa S3 and A549 cells were confirmed by fluorescence microscope in the presence of complexes 1 and 2 using AO (acridine orange, 200 µM) and EB (ethidium bromide, 100 µM). In addition, the docking results strongly support the protein binding studies of the complexes.Communicated by Ramaswamy H. Sarma.

N-substitution in isatin thiosemicarbazones decides nuclearity of Cu(II) complexes - Spectroscopic, molecular docking and cytotoxic studies.

The mono- (1) and bi-nuclear (2) copper(II) complexes containing N-substituted isatin thiosemicarbazone(s) were synthesized, and characterized by analytical and spectroscopic (UV-Visible, FT-IR and EPR) techniques. Bimetallic nature of complex 2 was confirmed by single crystal X-ray crystallography. The structures predicted by spectroscopic and crystallographic methods were validated by computational studies. From the spectroscopic, crystallographic and computational data, the structures were found to be distorted square planar for 1 and distorted square pyramidal for 2. Molecular docking studies showed hydrogen bonding and hydrophobic interactions of the complexes with tyrosinase kinase receptors. Complex 1 exhibited promising cytotoxic activity against Jurkat (leukemia) cell line, and complex 2 displayed more activity against HeLa S3 (cervical) and Jurkat cell lines with the IC50 values of 3.53 and 3.70 µM, respectively. Cytotoxicity of 1 (Jurkat) and 2 (Jurkat and HeLa S3) was better than that of cisplatin. Morphological changes in A549 (lung), HeLa S3 and Jurkat cell lines were examined in presence of the active complexes with the co-staining of Hoechst, AO (acridine orange) and EB (ethidium bromide) by fluorescence microscope.

ROS-Responsive Chitosan Coated Magnetic Iron Oxide Nanoparticles as Potential Vehicles for Targeted Drug Delivery in Cancer Therapy.

BACKGROUND AND OBJECTIVE: Cancer cells accumulate high concentrations of reactive oxygen species as a result of their faster and uninhibited metabolic activity. Cancer chemotherapeutic agents release an excess of severe adverse reactions as a result of targeting normal cells. This demands an improvement in targeted drug-delivery systems to selectively discharge anticancer drugs in the vicinity of such highly metabolically and mitotically active cells. MATERIALS AND METHODS: Here, magnetic nanoparticles were synthesized by a traditional co-precipitation technique. Fe3O4@OA-CS-5-FLU-NPs were synthesized by an easy and rapid in situ loading method. The proposed Fe3O4@OA-CS-5-FLU-NPs were productively prepared as well as characterized by various spectroscopic and microscopic studies. RESULTS: The targeted drug release profile of the Fe3O4@OA-CS-5-FLU-NPs was studied in the presence of ROS including H2O2 and pH induction. The released product, Fe3O4@OA-CS-5-FLU-NP, exhibited desirable levels of cytotoxicity and demonstrated morphological changes and inhibition of colony formation for A549 and HeLa S3 cancer cells. The IC50 values at 24 hours were 12.9 and 23 µg/mL, respectively. CONCLUSION: In summary, results from the MTT assay, fluorescence staining as well as colony formation assays, revealed that the Fe3O4@OA-CS-5-FLU-NPs were active and safe for anticancer biomedical applications. In summary, the present investigation provides a powerful nanostructured based system for improved cancer theranostics that should be further studied.

Amphiphilic Cationic Triscyclometalated Iridium(III) Complex-Peptide Hybrids Induce Paraptosis-like Cell Death of Cancer Cells via an Intracellular Ca2+-Dependent Pathway.

We report on the design and synthesis of a green-emitting iridium complex-peptide hybrid (IPH) 4, which has an electron-donating hydroxyacetic acid (glycolic acid) moiety between the Ir core and the peptide part. It was found that 4 is selectively cytotoxic against cancer cells, and the dead cells showed a green emission. Mechanistic studies of cell death indicate that 4 induces a paraptosis-like cell death through the increase in mitochondrial Ca2+ concentrations via direct Ca2+ transfer from ER to mitochondria, the loss of mitochondrial membrane potential (ΔΨm), and the vacuolization of cytoplasm and intracellular organelle. Although typical paraptosis and/or autophagy markers were upregulated by 4 through the mitogen-activated protein kinase (MAPK) signaling pathway, as confirmed by Western blot analysis, autophagy is not the main pathway in 4-induced cell death. The degradation of actin, which consists of a cytoskeleton, is also induced by high concentrations of Ca2+, as evidenced by costaining experiments using a specific probe. These results will be presented and discussed.

Unprecedented formation of palladium(II)-pyrazole based thiourea from chromone thiosemicarbazone and [PdCl2(PPh3)2]: Interaction with biomolecules and apoptosis through mitochondrial signaling pathway.

Two novel pyrazole based thiourea palladium(II) complexes, [PdCl(PPh3)(C9H8NO2S-pz)] (1) and [PdCl(PPh3)(C14H10NO2S-pz)] (2) [pz = pyrazole (C3H2N2)] have been obtained unexpectedly from chromone thiosemicarbazones (L1 and L2) and [PdCl2(PPh3)2]. The compounds have been fully characterized by physicochemical studies. The single crystal X-ray diffraction and spectral studies revealed square planar geometry for the complexes. The conversion of chromone thiosemicarbazone into pyrazole based thiourea might have happened through coordination to palladium(II) ion after enolization, Michael addition and ring opening followed by cyclization. To the best of our knowledge, this is the first report for the conversion of chromone thiosemicarbazone into pyrazole based thiourea moiety. Plausible mechanism was proposed based on the spectroscopic studies. Calf thymus (CT) DNA binding of the compounds was explored using various spectroscopic and molecular docking methods. DNA cleavage studies suggested that complexes 1 and 2 had the capacity to cleave the supercoiled DNA (pUC19) to its naked form. In vitro cytotoxic property of the ligands and complexes has been evaluated against three human cancer cells such as A549, HepG-2 and U937. Complex 2 exhibited potent cytotoxic activity against HepG-2 cells with the IC50 value of 10.4 µM. In addition, mechanistic studies showed that complex 2 induced apoptosis through mitochondrial signaling pathway in HepG-2 cells. Beneficially, complex 2 showed less toxicity against human lung (IMR90) normal cells and hence it emerges as a potential candidate for further studies.

Iron oxide nanoparticle core-shell magnetic microspheres: Applications toward targeted drug delivery.

This study describes a sensitive reactive oxygen species (ROS)-responsive lecithin (LEC) incorporated iron oxide nanoparticle (Fe3O4 NP) system with potent anti-inflammatory properties and even more so when the antioxidant drug curcumin (CUR) is encapsulated in the PLGA hybrid magnetic microsphere system (Fe3O4@LEC-CUR-PLGA-MMS). The delivery system is responsive to ROS including an H2O2 environment to release the payload (CUR) drug. Greater cytotoxicity properties were observed in the presence of Fe3O4@LEC-CUR-PLGA-MMS against A549 and HeLa S3 cells with IC50 values after 24 h of 10 and 12 µg/mL and 10 and 20 µg/mL, respectively. The present Fe3O4@LEC-CUR-PLGA-MMS system demonstrated much better in vitro cytotoxicity, cellular morphological changes and moreover an ability to limit colony formation for A549 and HeLa S3 cancer cell lines than non-cancerous cells, and thus, should be further studied for a wide range of medical applications.

A New Class of ß-Pyrrolidino-1,2,3-Triazole Derivatives as ß-Adrenergic Receptor Inhibitors: Synthesis, Pharmacological, and Docking Studies.

New 1,4-disubstituted ß-pyrrolidino-1,2,3-triazoles were synthesized using a reusable copper-iodide-doped neutral alumina catalyst. Synthesis of diversely substituted triazoles and recyclability of CuI catalyst explains the broad scope of this protocol. The synthesized compounds were screened for their antimicrobial and anticancer properties. Most of the compounds showed significant antimicrobial activities against all the tested microorganisms compared to standard drugs. Furthermore, compounds 5a, 5e, 5g, 5h, 5i, and 5j showed moderate to potent activities against A549 and HepG-2 cells. In addition, compounds 5g and 5h displayed potential cytotoxicity activity against A549 cells with IC50 values of 72 ± 3.21 and 58 ± 2.31 µM, respectively. The molecular docking study revealed that some of the synthesized compounds exhibited comparable binding as co-crystalized ligands with the DNA topoisomerase IV and anaplastic lymphoma kinase receptors.

Design, Synthesis, DNA/HSA Binding, and Cytotoxic Activity of Half-Sandwich Ru(II)-Arene Complexes Containing Triarylamine-Thiosemicarbazone Hybrids.

Organoruthenium complexes are potent alternatives for platinum-based complexes because of their superior anticancer activity. In this investigation, a series of new Ru(II)-arene complexes with triarylamine-thiosemicarbazone hybrid ligands with higher anticancer activity than cisplatin are reported. The molecular structure of the ligands and complexes was confirmed spectroscopically and supported by single-crystal X-ray crystallography. These complexes adopted a three-leg piano stool geometry. All the Ru(II)-arene complexes were systematically investigated for their in vitro cytotoxicity against human cervical (HeLa S3), lung (A549) cancer, and human normal lung (IMR-90) cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Interestingly, a pyrrolidine-attached Ru(II)-benzene complex exhibited superior activity against cancer cells with low IC50 values, and colony formation study showed complete inhibition at 5 and 10 µM concentration. Furthermore, morphological changes assessed by acridine orange and propidium iodide staining revealed that the cell death occurred by apoptosis. In addition, the interaction between synthesized Ru(II)-arene complexes and DNA/protein was explored by absorption and emission spectroscopy methods. These synthesized new organoruthenium complexes can be used for developing new metal-based anticancer drugs.

Design, synthesis, and anticancer activity of iridium(III) complex-peptide hybrids that contain hydrophobic acyl groups at the N-terminus of the peptide units.

In previous work, we reported on that Ir complex-cationic peptide hybrids (IPHs) that contain three KKGG or KKKGG sequences (K: lysine, G: glycine) induce cell death in cancer cells by an intracellular Ca2+-dependent pathway and function as luminescent detectors in dead cells. To identify the target biomolecules by photoaffinity labeling, we designed and synthesized IPH that contains a photoreactive and hydrophobic 4-[3-(trifluotomethyl)-3H-diazirine-3-yl]benzoyl (TFDB) group and found that it has more potent cytotoxicity against Jurkat cells than the previously prepared compounds. Herein, we report on the preparation of some new IPHs that contain hydrophobic acyl groups at the N-terminus of the peptide portions of the molecules. Among them, an IPH containing a n-dodecanoyl group was found to have much more potent cancer cell death activity and superior selectivity for cancer cells (Jurkat cells) over normal cells. The results of mechanistic studies suggest that the cell death of Jurkat cells is induced via different pathway from that induced by the previously synthesized IPHs. The results of this study are described herein.

Ancistrolikokine E3, a 5,8'-Coupled Naphthylisoquinoline Alkaloid, Eliminates the Tolerance of Cancer Cells to Nutrition Starvation by Inhibition of the Akt/mTOR/Autophagy Signaling Pathway.

PANC-1 human pancreatic cancer cells are characterized by their ability to proliferate aggressively under hypovascular and hypoxic conditions in the tumor microenvironment, displaying a remarkable tolerance to nutrition starvation. The antiausterity strategy is a new approach in anticancer drug discovery aiming at the identification of potent agents that inhibit preferentially the survival of tumor cells during a limited supply of nutrients and oxygen. The new 5,8'-coupled naphthyldihydroisoquinoline alkaloid ancistrolikokine E3 (4), isolated from the Congolese liana Ancistrocladus likoko, showed potent preferential cytotoxicity against PANC-1 cells under nutrient-deprived conditions, with a PC50 value of 2.5 µM, without exhibiting toxicity in normal, nutrient-rich medium. The compound was found to induce dramatic alterations in cell morphology, leading to cell death. Moreover, it inhibited significantly PANC-1 cell migration and colony formation in a concentration-dependent manner. This study on 4 provides the first live evidence of the effect of a naphthyldihydroisoquinoline alkaloid against PANC-1 cells in nutrient-deprived medium. Mechanistic investigations conducted suggest that compound 4 is a potent inhibitor of the activation of the Akt/mTOR pathway. Furthermore, it inhibited the expression levels of the key autophagy regulators Atg5, Atg12, Beclin-1, LC3-I, and LC3-II. The results demonstrated that ancistrolikokine E3 (4) is a potent early-stage inhibitor of the autophagy pathway in PANC-1 human pancreatic cancer cells. Ancistrolikokine E3 (4) and related naphthylisoquinoline alkaloids are promising potential lead compounds for anticancer drug development based on the antiausterity strategy.

Chemical Constituents of Thai Citrus hystrix and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line.

Human pancreatic cancer cells have an extreme tolerance to nutrition starvation, enabling them to survive in a hypovascular tumor microenvironment. Searching for agents that preferentially inhibit cancer cell viability under nutrition starvation conditions is a novel antiausterity strategy in anticancer drug discovery. In the present study, a hexane extract of the peels of Citrus hystrix fruits showed preferential cytotoxicity against PANC-1 human pancreatic cancer cells using a nutrient-deprived medium. Phytochemical investigation of this bioactive extract led to the isolation of 10 coumarins (1-10) including a new furanocoumarin (1). The isolated compounds were tested for their preferential cytotoxic activity against three different human pancreatic cancer cell lines [PANC-1, MIA PaCa-2, and PSN-1]. Among these, bergamottin (7) was identified as the most active constituent. In real-time live imaging, 7 was found to induce cell shrinkage, membrane blebbing, and disintegration of organelles in PANC-1 cells. Bergamottin (7) was also found to inhibit PANC-1 cell migration and colony formation. Mechanistically, 7 inhibited key survival proteins in the Akt/mTOR signaling pathway. Bergamottin (7) and related compounds are potential antiausterity candidates for drug development against pancreatic cancer.

Nickel(II) bis(isatin thiosemicarbazone) complexes induced apoptosis through mitochondrial signaling pathway and G0/G1 cell cycle arrest in IM-9 cells.

Three novel complexes (1, 3 and 4) ligating N-substituted isatin thiosemicarbazone derivatives have been synthesized and their structural and biological characteristics have been compared with those of the known analogs (2, 5-7 and 8). In addition, the structure of the representative ligands (L1, L3 and L4) and complex (4) was confirmed by single crystal X-ray diffraction method. All the complexes (1-8) were assessed for their cytotoxic property against a panel of four human cancer cells such as HepG-2 (liver), MOLM-14 (acute monocytic leukemia), U937 (histiocytic lymphoma). and IM-9 (myeloma). Complex 4 exhibited prominent cytotoxic property against MOLM-14, U937 and IM-9 cell lines. Moreover, the results were compared with the well-known anticancer drugs like doxorubicin, cisplatin and daunorubicin. Besides, complex 4 enhanced the apoptotic cell death in IM-9 cell line and induced cell cycle arrest at G1 phase. Western blot analysis revealed the down-regulation of Bcl-2 (b-cell lymphoma-2), up-regulation of Bax (bcl-2 associated X protein), release of cytochrome c and activation of caspases-3 in IM-9 cells by complex 4. Importantly, complex 4 was not toxic to the normal Vero cell line (IC50 > 300 µM). In addition, complex 4 showed the concentration dependent cleavage of supercoiled (SC) DNA to its nicked circular (NC) form.

Discovery of potential antiausterity agents from the Japanese cypress Chamaecyparis obtusa.

The chloroform extract of the Japanese cypress Chamaecyparis obtusa was found to kill PANC-1 human pancreatic cancer cells preferentially in the nutrient-deprived medium without causing toxicity in the nutrient rich condition. Phytochemical investigation on this extract led to the isolation of a new sesquiterpene (1), together with the six sesquiterpenes (2-7) and a lignan (8). The isolated compounds were tested for their preferential cytotoxicity activity against five different human pancreatic cancer cell lines [PANC-1, MIA PaCa2, CAPAN-1, PSN-1, and KLM-1] by utilizing an antiausterity strategy. Among them, α-cadinol (2) was identified as the most active constituent. α-Cadinol (2) was found to inhibit the activation of Akt/mTOR pathway, and the hyperactivation of autophagy leading to preferential PANC-1 cell death during nutrient-starvation.

Ru(II)-Catalyzed Regiospecific C-H/O-H Oxidative Annulation to Access Isochromeno[8,1-ab]phenazines: Far-Red Fluorescence and Live Cancer Cell Imaging.

A facile ruthenium(II)-catalyzed regiospecific C-H/O-H oxidative annulation methodology was developed to construct isochromeno[8,1-ab]phenazines. This methodology delivers various advantages, such as scope for diverse substrates, tolerance to a range of functional groups, stability under air, and yields regioselective products. This methodology was successfully applied to synthesize far red (FR) fluorescent probes for live cancer cell imaging. The synthesized compounds displayed notable fluorescence properties in solution and thin-film. Their application in live cancer cell imaging was investigated using various cancer cell lines. The synthesized compound showed prominent FR fluorescence, with high quantum yield, and exhibited better cell-imaging properties, with excellent biocompatibility.

Isolation and characterization of 2-hydroxy-9,10-anthraquinone from Streptomyces olivochromogenes (ERINLG-261) with antimicrobial and antiproliferative properties

Abstract Currently Streptomyces is one of the most important antibiotic producing microorganisms against several diseases. In the present study Streptomyces olivochromogenes ERINLG-261 was isolated from the soil samples of the Mudumalai hills, Western Ghats, India. Morphological, physiological, biochemical and 16S rRNA studies strongly suggested that this isolate belonged to the genus Streptomyces. ERINLG-261 showed good antimicrobial activity against different bacteria and fungi in Micromonospora fermentation medium. The active ethyl acetate extract was packed in column chromatography over silica gel which led to the isolation of 2-hydroxy-9,10-anthraquinone as the active principle. The isolated compound showed good antimicrobial activity against tested bacteria and fungi in minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) studies. The compound showed moderate in vitro antiproliferative activity against A549 and COLO320 cells. The compound was subjected to molecular docking studies for the inhibition of Topoisomerase, TtgR and Beta-lactamase enzymes which are targets for antimicrobials. Docking results of the compound showed low docking energy with these enzymes indicating its usefulness as antimicrobial agent. This is the first report of antimicrobial and antiproliferative activity of 2-hydroxy-9,10-anthraquinone isolated from Streptomyces olivochromogenes along with molecular docking studies.

Synthesis of cinnolines via Rh(iii)-catalysed dehydrogenative C-H/N-H functionalization: aggregation induced emission and cell imaging.

Rhodium catalysed dehydrogenative C-H/N-H functionalization was developed to construct phthalazino[2,3-a]-/indazolo[1,2-a]cinnolines by reacting N-phenyl phthalazine/indazole with alkynes. The synthesized compounds exhibit prominent fluorescence properties in solid and aggregation states. Their application in cell imaging was investigated using various cancer cell lines.