An Insight into Fluorinated Imines and Hydrazones as Antibacterial Agents.

Fluorinated imines (Schiff bases) and fluorinated hydrazones are of particular interest in medicinal chemistry due to their potential usefulness in treating opportunistic strains of bacteria that are resistant to commonly used antibacterial agents. The present review paper is focused on these fluorinated molecules revealing strong, moderate or weak in vitro antibacterial activities, which have been reported in the scientific papers during the last fifteen years. Fluorinated building blocks and reaction conditions used for the synthesis of imines and hydrazones are mentioned. The structural modifications, which have an influence on the antibacterial activity in all the reported classes of fluorinated small molecules, are highlighted, focusing mainly on the importance of specific substitutions. Advanced research techniques and innovations for the synthesis, design and development of fluorinated imines and hydrazones are also summarized.

Cardiotoxicity and ROS Protection Assessment of three Structure-Related N-Acylhydrazones with Potential for the Treatment of Neurodegenerative Diseases.

The senescence process is associated with accumulated oxidative damage and increased metal concentration in the heart and brain. Besides, abnormal metal-protein interactions have also been linked with the development of several conditions, including Alzheimer's and Parkinson's diseases. Over the years we have described a series of structure-related compounds with different activities towards models of such diseases. In this work, we evaluated the potential of three N-acylhydrazones (INHHQ: 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone, HPCIH: pyridine-2-carboxaldehyde isonicotinoyl hydrazone and X1INH: 1-methyl-1H-imidazole-2-carboxaldehyde isonicotinoyl hydrazone) to prevent oxidative stress in cellular models, with the dual intent of being active on this pathway and also to confirm their lack of cardiotoxicity as an important step in the drug development process, especially considering that the target population often presents cardiovascular comorbidity. The 8-hydroxyquinoline-contaning compound, INHHQ, exhibits a significant cardioprotective effect against hydrogen peroxide and a robust antioxidant activity. However, this compound is the most toxic to the studied cell models and seems to induce oxidative damage on its own. Interestingly, although not possessing a phenol group in its structure, the new-generation 1-methylimidazole derivative X1INH showed a cardioprotective tendency towards H9c2 cells, demonstrating the importance of attaining a compromise between activity and intrinsic cytotoxicity when developing a drug candidate.

Preparation of new organo-ruthenium(II) complexes and their nucleic acid/albumin binding efficiency and in vitro cytotoxicity studies.

Hetero-bimetallic ruthenium(II) complexes (PRAFIZ and PRBFIZ) containing acetyl ferrocene (AFIZ)/benzoyl ferrocene isonicotinic hydrazone ligands (BFIZ) were synthesized and characterized by various spectral and analytical techniques. The structure of acetyl ferrocene isonicotinic hydrazone (AFIZ) and the complex PRBFIZ was confirmed by X-ray crystallography. The hydrazide ligands coordinated in a bidentate monobasic fashion using their N1 hydrazinic nitrogen and enolic oxygen atoms. The binding interactions of the ligands and complexes were examined using Calf-Thymus DNA (CT-DNA) and bovine serum albumin (BSA). Scanning Electron Microscopic (SEM) experiments clarified the efficient binding interaction of the ligands and complexes with BSA. The results of in vitro cytotoxicity studies on MDA-MB-261 breast cancer cells and A549 human lung cancer cells and cell morphological analysis results through staining assays clearly indicated the cytotoxic nature of the complexes.

Aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamides as potent α-glucosidase inhibitors; molecular dynamics, kinetic and structure-activity relationship studies.

Regarding the important role of α-glucosidase enzyme in the management of type 2 diabetes mellitus, the current study was established to design and synthesize aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamide (11a-o) and the structure of all derivatives was confirmed through various techniques including IR, 1H-NMR, 13C-NMR and elemental analysis. Next, the α-glucosidase inhibitory potentials of all derivatives were evaluated, and all compounds displayed potent inhibition with IC50 values in the range of 26.0 ± 0.8-459.8 ± 1.5 µM as compared to acarbose used as control, except 11f and 11l. Additionally, in silico-induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the newly synthesized compounds over the active site of α-glucosidase.

ortho-Boronic Acid Carbonyl Compounds and Their Applications in Chemical Biology.

Iminoboronates and diazaborines are related classes of compounds that feature an imine ortho to an arylboronic acid (iminoboronate) or a hydrazone that cyclizes with an ortho arylboronic acid (diazaborine). Rather than acting as independent chemical motifs, the arylboronic acid impacts the rate of imine/hydrazone formation, hydrolysis, and exchange with competing nucleophiles. Increasing evidence has shown that the imine/hydrazone functionality also impacts arylboronic acid reactivity toward diols and reactive oxygen and nitrogen species (ROS/RNS). Untangling the communication between C=N linked functionalities and arylboronic acids has revealed a powerful and tunable motif for bioconjugation chemistries and other applications in chemical biology. Here, we survey the applications of iminoboronates and diazaborines in these fields with an eye toward understanding their utility as a function of neighboring group effects.

Synthesis of 3-hydroxy-2-naphthohydrazide-based hydrazones and their implications in diabetic management via in vitro and in silico approaches.

Diabetes mellitus (DM) has prevailed as a chronic health condition and has become a serious global health issue due to its numerous consequences and high prevalence. We have synthesized a series of hydrazone derivatives and tested their antidiabetic potential by inhibiting the essential carbohydrate catabolic enzyme, "α-glucosidase." Several approaches including fourier transform infrared, 1 H NMR, and 13 C NMR were utilized to confirm the structures of all the synthesized derivatives. In vitro analysis of compounds 3a-3p displayed more effective inhibitory activities against α-glucosidase with IC50 in a range of 2.80-29.66 µM as compared with the commercially available inhibitor, acarbose (IC50 = 873.34 ± 1.67 M). Compound 3h showed the highest inhibitory potential with an IC50 value of 2.80 ± 0.03 µM, followed by 3i (IC50 = 4.13 ± 0.06 µM), 3f (IC50 = 5.18 ± 0.10 µM), 3c (IC50 = 5.42 ± 0.11 µM), 3g (IC50 = 6.17 ± 0.15 µM), 3d (IC50 = 6.76 ± 0.20 µM), 3a (IC50 = 9.59 ± 0.14 µM), and 3n (IC50 = 10.01 ± 0.42 µM). Kinetics analysis of the most potent compound 3h revealed a concentration-dependent form of inhibition by 3h with Ki value = 4.76 ± 0.0068 µM. Additionally, an in silico docking approach was applied to predict the binding patterns of all the compounds, which indicates that the hydrazide and the naphthalene-ol groups play a vital role in the binding of the compounds with the essential residues (i.e., Glu277 and Gln279) of the α-glucosidase enzyme.

C-O Coupling of Hydrazones with Diacetyliminoxyl Radical Leading to Azo Oxime Ethers-Novel Antifungal Agents.

Selective oxidative C-O coupling of hydrazones with diacetyliminoxyl is demonstrated, in which diacetyliminoxyl plays a dual role. It is an oxidant (hydrogen atom acceptor) and an O-partner for the oxidative coupling. The reaction is completed within 15-30 min at room temperature, is compatible with a broad scope of hydrazones, provides high yields in most cases, and requires no additives, which makes it robust and practical. The proposed reaction leads to the novel structural family of azo compounds, azo oxime ethers, which were discovered to be highly potent fungicides against a broad spectrum of phytopathogenic fungi (Venturia inaequalis, Rhizoctonia solani, Fusarium oxysporum, Fusarium moniliforme, Bipolaris sorokiniana, Sclerotinia sclerotiorum).

Pyridyl-Isonicotinoyl Hydrazone-Bridged Zn(II) Coordination Framework with Thiophenedicarboxylato Link: Structure, Biological Activity, and Electrical Conductivity.

Multidimensional applicability of functional materials is one of the focal attractions in today's scientific research. Highly stable and crystalline coordination polymers served as one of the active members in the club of multifunctional materials. Toward this concept, a 3-dimensional (3D) coordination framework, {[Zn2(tdc)2(pcih)2]n} (1) (tdc2-, 2,5-thiophene dicarboxylate; pcih, pyridine-4-carboxaldehyde isonicotinoyl hydrazine), is designed and has been structurally well characterized by single crystal X-ray crystallography. One of the carboxylate groups of tdc2- chelates to Zn(II), while the other carboxylato group (-COO) acts as bridging-O to neighboring Zn(II); the pcih serves as pyridyl-N bridging motif to two Zn(II) centers. The optical band gap, 3.83 eV (Tauc's plot), implies probable semiconducting ability of the material. Interestingly, the device fabricated using compound 1 measures the electrical conductivity, 2.21 × 10-5 S cm-1, and series resistance (Rs), 807 Ω, at the dark phase, which are improved significantly to 6.36 × 10-5 S cm-1 and 460 Ω, respectively, under illumination conditions. Isoniazid, used to synthesize pcih and hence the Zn(II) compound 1, is a medicine; so, the medicinal efficiency of 1 is checked by measuring the anticancer activity against MDA-MB-231, HeLa, HCT-116, and HepG2 cells. It is observed that drug efficacy is highest on MDA-MB-231 cells (IC50: 19.43 ± 1.36 µM) than other cancer cells [IC50: 24.43 ± 2.02 µM (HeLa), 26.06 ± 3.48 µM (HCT-116), and 44.28 ± 3.04 µM (HepG2)]. Therefore, the material has significant contribution in the area of energy and health toward the sustainable development goals.

Hydrolytically Stable TiIV-Hydrazone-Based Metallodrugs: Protein Interaction and Anticancer Potential.

In this work, three titanium(IV) [TiIV(L1-3)2] (1-3) complexes have been reported using three different tridentate dibasic ONO donor hydrazone ligands, pyridine-4-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)-hydrazide (H2L1), furan-2-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)-hydrazide (H2L2), and thiophene-2-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)-hydrazide (H2L3) tethered with heterocyclic moieties. Elemental analysis, FT-IR, UV-vis, NMR, HR-ESI-MS, and single-crystal X-ray analysis have been used to characterize H2L1-3 and 1-3. In solid structures of 1-3, two ligand molecules with N2O4 donor sets give distorted octahedral geometries to the metal center. The aqueous stability of 1-3 was investigated and well correlated to their perceived pharmacological results. During the investigation, all three complexes were found to be hydrolytically stable in a 90% DMSO-d6/10% D2O (v/v) medium up to 48 h. Furthermore, the interaction of 1-3 with bovine serum albumin (BSA) was tested using fluorescence and absorption techniques. The complexes showed static quenching with a biomolecular quenching constant of Kq ∼ 1013 proposing a high affinity of complexes for BSA. Finally, the anticancer potential of 1-3 was tested against HeLa, A549, and NIH-3T3 cell lines. Among all, 1 with an IC50 value of 11.6 ± 1.1 µM against HeLa cells was found to be the most cytotoxic in the series. Furthermore, it has been found that the compounds induce an apoptotic mode of cell death, which is confirmed by the live cell confocal microscopy and flow cytometry techniques.

Design, Synthesis, and Bioactivity of Aldisine Derivatives Containing Oxime and Hydrazine Moieties Based on Hydrogen Bonds.

Marine natural products have attracted more and more attention in drug research and development due to their unique structure, diverse biological activities, and novel mode of action. Using antiviral alkaloid aldisine as the lead compound and drawing on the hydrogen bond effect widely used in drug design, derivatives containing oxime and hydrazone moieties were designed and synthesized by introducing functional groups with hydrogen-bond receptors or donors into molecules. The configuration of derivatives was systematically studied through nuclear Overhauser effect (NOE) spectroscopy and single crystal analysis. The antiviral activity test result showed that most derivatives had antiviral activity against tobacco mosaic virus (TMV), and some compounds had better activity than the commercial antiviral drug ribavirin, especially compounds 2 and 24, which had comparable activity to the most effective commercial antiviral drug ningnanmycin. Preliminary mode of action studies showed that compound 2 could affect the assembly of rod-shaped TMVs by promoting the aggregation and fragmentation of TMV coat proteins. Molecular docking experiments demonstrated that the introduction of oxime and hydrazone moieties could indeed increase the hydrogen bond between molecules and target proteins. In addition, we conducted fungicidal and larvicidal activities study of these derivatives. Most of these derivatives had good larvicidal activities against Mythimna separata and Plutella xylostella and showed broad-spectrum fungicidal activities.

Mechanochemical Studies on Coupling of Hydrazines and Hydrazine Amides with Phenolic and Furanyl Aldehydes-Hydrazones with Antileishmanial and Antibacterial Activities.

Hydrazone compounds represent an important area of research that includes, among others, synthetic approaches and biological studies. A series of 17 hydrazones have been synthesized by mechanochemical means. The fragments chosen were phenolic and furanyl aldehydes coupled with 12 heterocyclic hydrazines or hydrazinamides. All compounds can be obtained quantitatively when operating on a planetary ball mill and a maximum reaction time of 180 min (6 cycles of 30 min each). Complete spectroscopic analyses of hydrazones revealed eight compounds (3-5, 8-11, 16) present in one geometric form, six compounds (1, 2, 13-15) present in two isomeric forms, and three compounds (6, 7, 12) where one rotation is restricted giving rise to two different forms. The single crystal X-ray structure of one of the hydrazones bearing the isoniazid fragment (8) indicates a crystal lattice consisting of two symmetry-independent molecules with different geometries. All compounds obtained were tested for anti-infectious and antibacterial activities. Four compounds (1, 3, 5 and 8) showed good activity against Mycobacterium tuberculosis, and one (7) was very potent against Staphylococcus aureus. Most interesting, this series of compounds displayed very promising antileishmanial activity. Among all, compound 9 exhibited an IC50 value of 0.3 µM on the Leishmania donovani intramacrophage amastigote in vitro model and a good selectivity index, better than miltefosine, making it worth evaluating in vivo.

Synthesis, Biological, Spectroscopic and Computational Investigations of Novel N-Acylhydrazone Derivatives of Pyrrolo[3,4-d]pyridazinone as Dual COX/LOX Inhibitors.

Secure and efficient treatment of diverse pain and inflammatory disorders is continually challenging. Although NSAIDs and other painkillers are well-known and commonly available, they are sometimes insufficient and can cause dangerous adverse effects. As yet reported, derivatives of pyrrolo[3,4-d]pyridazinone are potent COX-2 inhibitors with a COX-2/COX-1 selectivity index better than meloxicam. Considering that N-acylhydrazone (NAH) moiety is a privileged structure occurring in many promising drug candidates, we decided to introduce this pharmacophore into new series of pyrrolo[3,4-d]pyridazinone derivatives. The current paper presents the synthesis and in vitro, spectroscopic, and in silico studies evaluating the biological and physicochemical properties of NAH derivatives of pyrrolo[3,4-d]pyridazinone. Novel compounds 5a-c-7a-c were received with high purity and good yields and did not show cytotoxicity in the MTT assay. Their COX-1, COX-2, and 15-LOX inhibitory activities were estimated using enzymatic tests and molecular docking studies. The title N-acylhydrazones appeared to be promising dual COX/LOX inhibitors. Moreover, spectroscopic and computational methods revealed that new compounds form stable complexes with the most abundant plasma proteins-AAG and HSA, but do not destabilize their secondary structure. Additionally, predicted pharmacokinetic and drug-likeness properties of investigated molecules suggest their potentially good membrane permeability and satisfactory bioavailability.

New Anthranilic Acid Hydrazones as Fenamate Isosteres: Synthesis, Characterization, Molecular Docking, Dynamics & in Silico ADME, in Vitro Anti-Inflammatory and Anticancer Activity Studies.

In this study, twenty new anthranilic acid hydrazones 6-9 (a-e) were synthesized and their structures were characterized by Fourier-transform Infrared (FT-IR), Nuclear Magnetic Resonance (1 H-NMR - 13 C-NMR), and High-resolution Mass Spectroscopy (HR-MS). The inhibitory effects of the compounds against COX-II were evaluated. IC50 values of the compounds were found in the range of >200-0.32 µM and compounds 6e, 8d, 8e, 9b, 9c, and 9e were determined to be the most effective inhibitors. Cytotoxic effects of the most potent compounds were investigated against human hepatoblastoma (Hep-G2) and human healthy embryonic kidney (Hek-293) cell lines. Doxorubicin (IC50 : 8.68±0.16 µM for Hep-G2, 55.29±0.56 µM for Hek-293) was used as standard. 8e is the most active compound, with low IC50 against Hep-G2 (4.80±0.04 µM), high against Hek-293 (159.30±3.12), and high selectivity (33.15). Finally, molecular docking and dynamics studies were performed to understand ligand-protein interactions between the most potent compounds and COX II, Epidermal Growth Factor Receptor (EGFR), and Transforming Growth Factor beta II (TGF-ßII). The docking scores were calculated in the range of -10.609--6.705 kcal/mol for COX-II, -8.652--7.743 kcal/mol for EGFR, and -10.708--8.596 kcal/mol for TGF-ßII.

Cuminaldehyde-3-hydroxy-2-napthoichydrazone: Synthesis, effect of solvents, nonlinear optical activity, antioxidant activity, antimicrobial activity, and DFT analysis.

Hydrazones derived from essential oil components have attracted considerable interest because of their antimicrobial, antioxidant, and nonlinear optical applications. In the present work, a new essential oil component derivative (EOCD), cuminaldehyde-3-hydroxy-2-napthoichydrazone (CHNH), was synthesized. EOCD was characterized by Fourier transform infrared spectroscopy, mass spectrometry, nuclear magnetic resonance (1H and 13C) spectroscopy, elemental analysis, ultraviolet-visible absorption spectroscopy, and field-emission scanning electron microscopy. Thermogravimetric analysis and X-ray diffraction showed a higher stability, phase-pure, and non-existent isomorphic phase transition in EOCD. Solvent studies indicated that the normal emission band was caused by the locally excited state and the large Stokes shifted emission originated because of the twisted intramolecular charge transfer. The EOCD possessed higher direct and indirect band gap energies of 3.05 eV and 2.90 eV respectively, as determined by the Kubelka-Munk algorithm. The outcomes of frontier molecular orbitals, global reactivity descriptors, Mulliken, and molecular electrostatic potential surface by density functional theory calculations revealed high intramolecular charge transfer, good realistic stability, and high reactiveness of EOCD. The hydrazone EOCD exhibited higher hyperpolarizability (18.248 × 10-30 esu) in comparison to urea. Antioxidant test results indicated that EOCD showed significant antioxidant activity (p < 0.05), as determined by the DPPH radical scavenging assay. The newly synthesized EOCD showed no antifungal activity against Aspergillus flavus. Additionally, the EOCD showed good antibacterial activity against Escherichia coli and Bacillus subtilis.

Synthesis, anti-ferroptosis, anti-quorum sensing, antibacterial and DNA interaction studies of chromene-hydrazone derivatives.

Nineteen chromene-hydrazone derivatives containing a variety of structural modifications on the hydrazone moiety were synthesized. Structure-activity correlations were investigated to determine the influence of structural variations on anti-ferroptosis, anti-quorum sensing, antibacterial, DNA cleavage and DNA binding properties. Ferroptosis inhibitory activity was determined by measuring the ability of the derivatives to reverse erastin-induced ferroptosis. Several of the derivatives were more effective than fisetin at inhibiting ferroptosis, with the thiosemicarbazone derivative being the most effective. Quorum sensing inhibition was evaluated using Vibrio harveyi, and both V. harveyi and Staphylococcus aureus were used to determine antibacterial activity. The semicarbazone and benzensulfonyl hydrazone derivatives showed moderate quorum sensing inhibition with IC50 values of 27 µM and 22 µM, respectively, while a few aryl hydrazone and pyridyl hydrazone derivatives showed bacterial growth inhibition, with MIC values ranging from 3.9 to 125 µM. In addition, the interaction of the hydrazone derivatives with DNA was investigated by gel electrophoresis, UV-Vis spectroscopy and molecular docking. All of the derivatives cleaved plasmid DNA and showed favorable interaction with B-DNA through minor groove binding. Overall, this work highlights a broad range of pharmacological applications for chromene-hydrazone derivatives.

Geometry and UV-Vis Spectra of Au3+ Complexes with Hydrazones Derived from Pyridoxal 5'-Phosphate: A DFT Study.

Gold(III) complexes with different ligands can provide researchers with a measure against pathogenic microorganisms with antibiotic resistance. We reported in our previous paper that the UV-Vis spectra of different protonated species of complexes formed by gold(III) and five hydrazones derived from pyridoxal 5'-phosphate are similar to each other and to the spectra of free protonated hydrazones. The present paper focuses on the reasons of the noted similarity in electron absorption spectra. The geometry of different protonated species of complexes of gold(III) and hydrazones (15 structures in total) was optimized using the density functional theory (DFT). The coordination polyhedron of gold(III) bond critical points were further studied to identify the symmetry of the gold coordination sphere and the type of interactions that hold the complex together. The UV-Vis spectra were calculated using TD DFT methods. The molecular orbitals were analyzed to interpret the calculated spectra.

A Comprehensive Investigation of Hydrazide and Its Derived Structures in the Agricultural Fungicidal Field.

Hydrazides are present in many bioactive molecules and exhibit a variety of biological activities, such as insecticidal, herbicidal, antifungal, antitumor, and antiviral effects. In this Review, we review the application of hydrazide and its derived structures in the agricultural fungicidal field, including monohydrazides, diacylhydrazines, hydrazide-hydrazones, and sulfonyl hydrazides. In addition, the antifungal mechanism of action of the hydrazide derivatives was analyzed and summarized, mainly involving succinate dehydrogenase inhibitors, laccase inhibitors, and targeting plasma membranes. Finally, based on the structural analysis of the novel fungicidal lead compounds, the structure-activity relationship of the hydrazide derivatives was constructed and the development trend of hydrazide structures in fungicidal applications was prospected. It is hoped that this Review can provide some significant guidance for the development of new hydrazide fungicides in the future.

Synthesis, in silico and in vitro studies of hydrazide-hydrazone imine derivatives as potential cholinesterase inhibitors.

A series of hydrazide-hydrazone imine derivative compounds (3a-k) were synthesized and their structures characterized using FTIR, 1 H, and 13 C (NMR) spectroscopic methods. In addition, molecular structures of compounds 3a, 3d, and 3g were elucidated by X-ray diffraction technique. In vitro inhibition activities of hydrazide-hydrazone imine derivatives against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were investigated. Compound 3i (IC50 = 2.01 µM) exhibited the best inhibitory activity against AChE, comparable to the control Galantamine (IC50 = 2.60 µM). Against BChE, compound 3h (IC50 = 2.83 µM) showed the best inhibitory property which is higher control Galantamine (IC50 = 3.70 µM). The Ki values of compound 3i (Ki = 0.63 µM) and compound 3h (Ki = 0.94 µM) that have the strongest inhibitory potential were determined against AChE and BChE, respectively. According to the docking result, the most stable conformation of AChE and compound 3i showed that it has a binding affinity of -10.82 kcal/moL. The binding affinity of the most stable conformation formed by BChE and compound 3h is -8.60 kcal/moL. Finally, in silico results and pharmacokinetic parameters of ADME showed that these compounds have good oral bioavailability properties.

Design, Synthesis and Cytotoxic Activity of Novel Salicylaldehyde Hydrazones against Leukemia and Breast Cancer.

Despite the significant advancements in complex anticancer therapy, the search for new and more efficient specific anticancer agents remains a top priority in the field of drug discovery and development. Here, based on the structure-activity relationships (SARs) of eleven salicylaldehyde hydrazones with anticancer activities, we designed three novel derivatives. The compounds were tested in silico for drug-likeness, synthesized, and evaluated in vitro for anticancer activity and selectivity on four leukemic cell lines (HL-60, KE-37, K-562, and BV-173), one osteosarcomic cell line (SaOS-2), two breast adenocarcinomic cell lines (MCF-7 and MDA-MB-231), and one healthy cell line (HEK-293). The designed compounds were found to have appropriate drug likeness and showed anticancer activities in all cell lines tested; particularly, two of them exhibited remarkable anticancer activity in nanomolar concentrations on the leukemic cell lines HL-60 and K-562 and the breast cancer MCF-7 cells and extraordinary selectivity for the same cancer lines ranging between 164- and 1254-fold. The study also examined the effects of different substituents on the hydrazone scaffold and found that the 4-methoxy salicylic moiety, phenyl, and pyridinyl rings are the most appropriate for anticancer activity and selectivity of this chemical class.

Caging of Bodipy Photosensitizers through Hydrazone Bond Formation and their Activation Dynamics.

Three unique hydrazone-based small-molecule-activatable photosensitizers were designed and synthesized. Two of them work efficiently in a low-pH environment, resembling the microenvironment of the cancerous tissues. The activation pathway is unique and based on hydrazone bond cleavage. They were investigated through in vitro cellular studies in aggressive cancer lines, and tumor-specific culture conditions successfully initiated the cleavage and activation of the cytotoxic singlet oxygen generation in the relevant time period. The interesting photophysical characteristics of the α- and ß-substituted hydrazone derivatives of the Bodipy structures and their mild hydrolysis methodologies were also investigated successfully.