Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA.

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.

Dihydroxanthene-based monoamine oxidase A-activated photosensitizers for photodynamic/photothermal therapy of tumors.

Small molecule photosensitizers for combined in vivo tailored cancer diagnostics and photodynamic/photothermal therapy are desperately needed. Monoamine oxidase A (MAO-A)-activated therapeutic and diagnostic compounds provide great selectivity because MAO-A can be employed as a biomarker for associated Tumors. In order to screen photosensitizers with photodynamic therapeutic potential, we have created a range of near-infrared fluorescent molecules in this work by combining dihydroxanthene parent with various heterocyclic fluorescent dyes. The NIR fluorescent diagnostic probe, DHMQ, was created by combining the screened fluorescent dye matrices with the propylamino group, which is the recognition moiety of MAO-A, based on the oxidative deamination mechanism of the enzyme. This probe has a low toxicity level and can identify MAO-A precisely. It has the ability to use fluorescence imaging on mice and cells to track MAO-A activity in real-time. It has strong phototoxicity and can produce singlet oxygen when exposed to laser light. The temperature used in photothermal imaging can get up to 50 °C, which can harm tumor cells permanently and have a positive phototherapeutic impact on tumors grown from SH-SY5Y xenograft mice. The concept of using MAO-A effectively in diseases is expanded by the MAO-A-activated diagnostic-integrated photosensitizers, which offer a new platform for in vivo cancer diagnostics and targeted anticancer treatment.

Ionic Liquids Immobilized Synthesis of New Xanthenes Derivatives and their Antiproliferative, Molecular Docking, and Morphological Studies.

BACKGROUND: Xanthenes and benzoxanthenesare are highly valuable compounds in organic chemistry and medicinal chemistry. Xanthene derivatives were found to have many applications in medicinal chemistry. OBJECTIVE: This work aims to explore the synthesis of xanthene derivatives with various substituents and find the possibility of their uses as anticancer agents. METHODS: The basic starting compound through this work was the 2,3-dihydro-1H-xanthen-1-one (3), which was synthesized from the reaction of cyclohexan-1,3-dione and 2-hydroxybenzaldehyde. Compound 3 was used to synthesize new thiophene, pyrimidine, isoxazole, and thiazole derivatives based on the xanthenes nucleus. Fused xanthene derivatives were obtained through further heterocyclization reactions. Multicomponent reactions expressed in this work were carried out in the presence of solvent catalyzed by Et3N and in solvent-free ionic liquid immobilized catalyst. RESULTS: Cytotoxicity for the newly synthesized compounds toward cancer cell lines was measured, and the results revealed that many compounds exhibited high inhibitions. CONCLUSION: The antiproliferative activity of the synthesized compounds was studied on six selected cancer cell lines. The nature of the heterocyclic ring and the variations of substituted groups showed a high effect through the inhibitions of the tested compound.

The Design, Synthesis, and Evaluation of Novel 9-Arylxanthenedione-Based Allosteric Modulators for the δ-Opioid Receptor.

Chronic pain and depression are both widely prevalent comorbid medical conditions. While efficient, µ-opioid receptor-based medications are associated with life-threatening side effects, including respiratory depression, dependence, and addiction. The δ-opioid receptor is a promising alternative biological target for chronic pain and depression due to its significantly reduced on-target side effects compared to the µ-opioid receptor. A previous study identified two δ-opioid receptor positive allosteric modulators. Herein, we report the design of five series of compounds targeting previously unexplored regions of the originally described SAR. Analogs were assessed for their ability to potentiate the agonist response of Leu-enkephalin. Of the 30 analogs, compound 6g displayed trends toward enhancing the ERK1/2 phosphorylation signaling compared to cAMP inhibition, while compound 11c exhibited a trend in shifting the signaling bias toward cAMP inhibition. Both 6g and 11c emerged as promising tool compounds toward the design of prospective therapeutics requiring specific downstream signaling attributes.

Discovery of potent antiproliferative agents from selected oxygen heterocycles as EGFR tyrosine kinase inhibitors from the U.S. National Cancer Institute database by in silico screening and bioactivity evaluation.

A similarity search was conducted on the U.S. Enhanced National Cancer Institute Database Browser 2.2 to find structures related to 1,5-dihydroxy-9H-xanthen-9-one, a previously established EGFR-TK inhibitor. Compounds were virtually screened and selected for bioactivity testing revealed 5 candidates, mostly displayed stronger antiproliferative activities than erlotinib with IC50 values between 0.95 and 17.71 µM against overexpressed EGFR-TK cancer cell lines: A431 and HeLa. NSC107228 displayed the strongest antiproliferative effects with IC50 values of 2.84 and 0.95 µM against A431 and HeLa cancer cell lines, respectively. Three compounds, NSC81111, NSC381467 and NSC114126 inhibited EGFR-TK with IC50 values between 0.15 and 30.18 nM. NSC81111 was the best inhibitor with IC50 = 0.15 nM. Molecular docking analysis of the 3 compounds predicted hydrogen bonding and hydrophobic interactions with key residues were important for the bioactivities observed. Furthermore, calculations of the physicochemical properties suggest the compounds are drug-like and are potentially active orally.

Facile and divergent optimization of chromazonarol enabled the identification of simplified drimane meroterpenoids as novel pharmaceutical leads.

The diversity of drimane hydroquinones was significantly expanded by the facile construction of (+)-chromazonarol relevant natural products, isomers, and analogues for the discovery of new pharmaceutical leads. The structure-activity relationship of (+)-chromazonarol relevant (non)-natural products was delineated via the synergistic interaction of the programmable synthesis and bioactivity-guided screening. The first divergent derivatization of (+)-chromazonarol demonstrated that the phenolic hydroxyl group is one inviolable requirement for antifungal effect. Pinpoint modification of (+)-yahazunol manifested the position of hydroxyl group was crucial for both antifungal and antitumor activities. (+)-Albaconol, (+)-neoalbaconol, and two (+)-yahazunol isomers (24 and 25) proved to be the novel pharmaceutical leads. The probable macromolecular targets were estimated to deliver new information about the biological potentials resident in (+)-yahazunol relevant products. This work also featured the first synthesis of (+)-albaconol and (+)-neoalbaconol, the first biological exploration of (+)-dictyvaric acid and improved preparation of (+)-8-epi-puupehedione and a promising pelorol analogue.

Experimental and Computational Studies on the Ruthenium-Catalyzed Dehydrative C-H Coupling of Phenols with Aldehydes for the Synthesis of 2-Alkylphenol, Benzofuran, and Xanthene Derivatives.

The cationic Ru-H complex [(C6H6)(PCy3)(CO)RuH]+BF4- (1) was found to be an effective catalyst for the dehydrative C-H coupling reaction of phenols and aldehydes to form 2-alkylphenol products. The coupling reaction of phenols with branched aldehydes selectively formed 1,1-disubstituted benzofurans, while the coupling reaction with salicylaldehydes yielded xanthene derivatives. A normal deuterium isotope effect was observed from the coupling reaction of 3-methoxyphenol with benzaldehyde and 2-propanol/2-propanol-d8 (kH/kD = 2.3 ± 0.3). The carbon isotope effect was observed on the benzylic carbon of the alkylation product from the coupling reaction of 3-methoxyphenol with 4-methoxybenzaldehyde (C(3) 1.021(3)) and on both benzylic and ortho-arene carbons from the coupling reaction with 4-trifluorobenzaldehdye (C(2) 1.017(3), C(3) 1.011(2)). The Hammett plot from the coupling reaction of 3-methoxyphenol with para-substituted benzaldehydes p-X-C6H4CHO (X = OMe, Me, H, F, Cl, CF3) displayed a V-shaped linear slope. Catalytically relevant Ru-H complexes were observed by NMR from a stoichiometric reaction mixture of 1, 3-methoxyphenol, benzaldehyde, and 2-propanol in CD2Cl2. The DFT calculations provided a detailed catalysis mechanism featuring an electrophilic aromatic substitution of the aldehyde followed by the hydrogenolysis of the hydroxy group. The calculations also revealed a mechanistic rationale for the strong electronic effect of the benzaldehdye substrates p-X-C6H4CHO (X = OMe, CF3) in controlling the turnover-limiting step. The catalytic C-H coupling method provides an efficient synthetic protocol for 2-alkylphenols, 1,1-disubstituted benzofurans, and xanthene derivatives without employing any reactive reagents or forming wasteful byproducts.

ChCl: Gly (DESs) Promote Environmentally Benign Synthesis of Xanthene Derivatives and Their Antitubercular Activity.

A ChCl: Gly (DESs) promoted environmentally benign method was developed for the first time using the reaction of aryl aldehydes and dimedone to give excellent yields of xanthene analogues. The major application of this present protocol is the use of green solvent, a wide range of substrate, short reaction times, ease of recovery, the recyclability of the catalyst, high reaction yield, and ChCl: Gly as an alternative catalyst and solvent. In addition to this, all the synthesized compounds were evaluated for their in vitro antimycobacterial activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. The compounds 3d, 3e, 3f, and 3j showed significant antitubercular activity against MTB and M. bovis strains with minimum inhibitory concentration (MIC) values of 2.5-15.10 µg/mL and 0.26-14.92 µg/mL, respectively. The compounds 3e, 3f, and 3j were found to be nontoxic against MCF-7, A549, HCT 116, and THP-1 cell lines. All the prepared compounds were confirmed by 1H NMR and 13C NMR analysis.

Designing a novel photoinduced electron transfer-based small-molecule fluorescent probe specific for CYP3A isozymes.

Cytochrome P450 (CYPs) are oxidoreductases distributed in various tissues in plants and animals. Among the CYP families, CYP3A is the most abundant in vivo, particularly in humans, and it is involved in the metabolism of many drugs. It is crucial to measure CYP3A activity for both pharmaceuticals and agrochemicals because inhibition or induction of this enzyme can seriously affect the occurrence of toxicity or efficacy. In the present study, a novel fluorescent probe, 6-(2,5-bis(trifluoromethyl)benzyloxy)-9-(4-methoxy-2-methylphenyl)-3H-xanthen-3-one (BMX, quantum efficiency: 21%), was designed and synthesized. The design was done by photoinduced electron transfer strategy. BMX was specifically metabolized only using CYP3A to generate 2-Me-4-MeO TokyoGreen (quantum efficiency: 85%), resulting in strong fluorescence in the presence of CYP3A isozymes. Protein assays using recombinant human, rat, and mouse CYP isozymes demonstrated the selective metabolism of BMX and production of fluorescence only by CYP3A in all species.

Multi-component Reactions of Cyclohexan-1,3-diketones to Produce Fused Pyran Derivatives with Antiproliferative Activities and Tyrosine Kinases and Pim-1 Kinase Inhibitions.

In this work the multi-component reactions of either of the arylhydrazocyclohexan-1,3-dione derivatives 3a-c with either of benzaldehyde (4a), 4-chlorobenzaldehyde (4b) or 4-methoxybenzaldehyde (4c) and either malononitrile (5a) or ethyl cyanoacetate (5b) giving the 5,6,7,8-tetrahydro-4H-chromene derivatives 6a-r, respectively, are presented. The reaction of two equivalents of cyclohexan-1,3-dione with benzaldehyde gave the hexahydro-1H-xanthene-1,8(2H)-dione derivative 7. On the other hand, the multi-component reactions of compound 1 with dimedone and benzaldehyde gave 13. Both of 7 and 13 underwent heterocyclization reactions to produce fused thiophene, pyran and thiazole derivatives. Selected compounds among the synthesized compounds were tested against six cancer cell lines where most of them gave high inhibitions; especially compounds 3b, 3c, 6b, 6c, 6d, 6f, 6i, 6m, 6n, 8b, 14a, 15 and 16 being the most cytotoxic compounds. Further tests against the five tyrosine kinases c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR and Pim-1 kinase showed that compounds 3c, 6c, 6d, 6f, 6n, 14a and 15 were the most potent of the tested compounds toward the five tyrosine kinases and compounds 3c, 6c, 6d, 6n and 15 displayed the highest inhibitions toward Pim-1 kinase.

Xanthenylacetic Acid Derivatives Effectively Target Lysophosphatidic Acid Receptor 6 to Inhibit Hepatocellular Carcinoma Cell Growth.

Despite the increasing incidence of hepatocellular carcinoma (HCC) worldwide, current pharmacological treatments are still unsatisfactory. We have previously shown that lysophosphatidic acid receptor 6 (LPAR6) supports HCC growth and that 9-xanthenylacetic acid (XAA) acts as an LPAR6 antagonist inhibiting HCC growth without toxicity. Here, we synthesized four novel XAA derivatives, (±)-2-(9H-xanthen-9-yl)propanoic acid (compound 4 - MC9), (±)-2-(9H-xanthen-9-yl)butanoic acid (compound 5 - MC6), (±)-2-(9H-xanthen-9-yl)hexanoic acid (compound 7 - MC11), and (±)-2-(9H-xanthen-9-yl)octanoic acid (compound 8 - MC12, sodium salt) by introducing alkyl groups of increasing length at the acetic α-carbon atom. Two of these compounds were characterized by X-ray powder diffraction and quantum mechanical calculations, while molecular docking simulations suggested their enantioselectivity for LPAR6. Biological data showed anti-HCC activity for all XAA derivatives, with the maximum effect observed for MC11. Our findings support the view that increasing the length of the alkyl group improves the inhibitory action of XAA and that enantioselectivity can be exploited for designing novel and more effective XAA-based LPAR6 antagonists.

Indium-Catalyzed Aromative Spiro Coupling of Quinones with Oxindoles for Highly Functionalized Xanthenes as Efficient Fluorophores.

A convenient and an efficient protocol for the assembly of diverse xanthenes bearing a biologically interesting oxindole nucleus is developed by utilizing the In(III)-catalyzed spiro coupling of 1,4-benzoquinones or 1,4-naphthoquinones with oxindoles. This novel protocol proceeds via a cascade of double Michael additions and intramolecular cyclization. The synthesized compounds have potential use as fluorophores for the selective imaging of heavy metals in living cells.

Application of cyclohexane-1,3-diones for six-membered oxygen-containing heterocycles synthesis.

Cyclohexan-1,3-dione derivatives are versatile scaffolds for the synthesis of a variety of value-added organic molecules including heterocycles and natural products. Six-membered oxygen heterocycles prepared from cyclohexan-1,3-diones are of much importance as they are intermediate for the synthesis of a number of natural products and several other valuable bioactive molecules which shows anti-viral, anti-bacterial, analgesic, antimalarial, anti-inflammatory, anti-allergic, anti-tumor and anti-cancer activities. These advantages have inspired us to write a detailed survey on the newly developed methods which are very essential in the construction of six-membered oxygen heterocycles. Further, the versatility in the chemistry of cyclohexan-1,3-dione and its derivatives is due to the presence of highly active methylene moiety and its active di-carbonyl groups. Recently, reactions of cyclohexane-1,3-dione and its derivatives with other substrates for instance aldehydes, malononitriles, NMSM, chalcones, isatin etc. have been established for the construction of a variety of six-membered oxygen heterocycles. The studies reported in this review article involved the synthesis of six-membered oxygen-containing heterocycles which includes 4H-chromen-5(6H)-one, 2H-xanthen-1(9H)-one, 2H-xanthen-1,8(5H,9H)-dione, 6H-chromen-2,5-dione derivatives and natural products having six-membered oxygen heterocycles from cyclohexane-1,3-dione and its derivatives as one of the substrate.

Activated Carbon/MoO3: Efficient Catalyst for Green Synthesis of Chromeno[d]pyrimidinediones and Xanthenones.

BACKGROUND: Nanoscale metal oxide catalysts have been extensively employed in organic reactions because they have been found to influence the chemical and physical properties of bulk material. The chromene (benzopyran) nucleus constitutes the core structure in a major class of many biologically active compounds, and interest in their chemistry consequently continues because of their numerous biological activities. The xanthene (dibenzopyran) derivatives are classified as highly significant compounds which display a number of various bioactive properties. Pyrimidinones have also gained interest due to their remarkable biological utilization, such as antiviral, antibacterial, antihypertensive, antitumor, and calcium blockers effects. OBJECTIVE: The aim of this work presented herein was to prepare activated carbon/MoO3 nanocomposite and explore its role as a green and recyclable catalyst for the synthesis of chromeno[d]pyrimidinediones and xanthenones under ethanol-drop grinding at room temperature. METHODS: The activated carbon/MoO3 nanocomposite was prepared successfully via a simple route in which the carbonization of gums as new natural precursors was used for the synthesis of activated carbon. This nanocomposite was then effectively used in a reaction of 3,4-methylenedioxyphenol, aromatic aldehydes, and active methylene compounds, including 1,3-dimethylbarbituric acid and dimedone, to synthesize a series of chromeno[d]pyrimidinediones and xanthenones in high yields. The synthesized catalyst was characterized by Fourier transform infrared spectroscopy (FT-IR), Powder x-ray diffractometry (XRD), Scanning electron microscope (SEM), Raman spectroscopy, and also by TGA analysis. Confirmation of the structures of compounds 5(a-g) and 6(a-g) were also established with IR, 1H NMR, and 13C NMR spectroscopic data and also by elemental analyses. RESULTS: A number of 6,8-dimethyl-10-phenyl-6,10-dihydro-7H-[1,3]dioxolo[4´,5´:6,7]chromeno[2,3- d]pyrimidine-7,9(8H)-diones and 7,7-dimethyl-10-(4-methylphenyl)-6,7,8,10-tetrahydro-9H-[1,3]dioxolo[ 4,5-b]xanthen-9-ones were effectively synthesized using activated carbon/MoO3 nanocomposite (0.05 gr) as a catalyst under ethanol-drop grinding at room temperature. The desired products were obtained in high yields (93-97%) within short reaction times (15-20 min). CONCLUSION: This paper investigates the catalytic potential of the synthesized activated carbon/MoO3 nanocomposite for the preparation of chromeno[d]pyrimidinediones and xanthenones under the ethanol-drop grinding procedure. The mildness of the reaction conditions, high yields of products, short reaction times, experimental simplicity, and avoiding the use of harmful solvents or reagents makes this procedure preferable for the synthesis of these compounds.

Real-time imaging of alkaline phosphatase activity of diabetes in mice via a near-infrared fluorescent probe.

A novel water-soluble near-infrared fluorescent probe named QX-P with simple synthesis is developed. QX-P has high sensitivity and selectivity to ALP. Moreover, the probe can not only visualize ALP activity in four cell lines, but also real-time image ALP activity during the diagnosis and treatment of diabetes in mice.

Xanthenes in Medicinal Chemistry - Synthetic strategies and biological activities.

BACKGROUND: Xanthenes are a special class of oxygen-incorporating tricyclic compounds. Structurally related to xanthones, the presence of different substituents in position 9 strongly influences their physical and chemical properties, as well as their biological applications. This review explores the synthetic methodologies developed to obtain 9H-xanthene, 9-hydroxyxanthene and xanthene-9-carboxylic acid, as well as respective derivatives, from simple starting materials or through modification of related structures. Azaxanthenes, bioisosteres of xanthenes, are also explored. Efficiency, safety, ecological impact and applicability of the described synthetic methodologies are discussed. Synthesis of multi-functionalized derivatives with drug-likeness properties are also reported and their activities explored. Synthetic methodologies for obtaining (aza)xanthenes from simple building blocks are available, and electrochemical and/or metal free procedures recently developed arise as greener and efficient methodologies. Nonetheless, the synthesis of xanthenes through the modification of the carbonyl in position 9 of xanthones represents the most straightforward procedure to easily obtain a variety of (aza)xanthenes. (Aza)xanthene derivatives displayed biological activity as neuroprotector, antitumor, antimicrobial, among others, proving the versatility of this nucleus for different biological applications. However, in some cases their chemical structures suggest a lack of pharmacokinetic properties being associated with safety concerns, which should be overcome if intended for clinical evaluation.

A lysosome-targeting viscosity-sensitive fluorescent probe based on a novel functionalised near-infrared xanthene-indolium dye and its application in living cells.

The viscosity of lysosomes plays a significant role in modulating biological processes and reflects the status and function of this kind of organelle, e.g., locations, morphologies, and components. Herein, we constructed a novel near-infrared (NIR) lysosome-targeting viscosity probe, Lyso-cy, for monitoring viscosity changes in biological systems. The Lyso-cy probe showed very strong fluorescence emission at around 710 nm in viscous media. The fluorescence intensity of Lyso-cy increased 122-fold from when in water to when in 95% glycerol. Moreover, Lyso-cy proved to be an ideal lysosome-targeting tracer for monitoring fluctuations in the viscosity of a living cell with high spatial and temporal resolution under laser confocal microscopy.

Synthesis, DNA/RNA-interaction and biological activity of benzo[k,l]xanthene lignans.

Interactions of two newly synthesized and six previously reported benzoxanthene lignans (BXLs), analogues of rare natural products, with DNA/RNA, G-quadruplex and HSA were evaluated by a set of spectrophotometric methods. Presence/absence of methoxy and hydroxy groups on the benzoxanthene core and minor modifications at C-1/C-2 side pendants - presence/absence of phenyl ring and presence/absence of methoxy and hydroxy groups on phenyl ring - influenced the fluorescence changes and the binding strength to double-stranded (ds-) and G-quadruplex structures. In general, compounds without phenyl ring showed stronger fluorescence changes upon binding than phenyl-substituted BXLs. On the other hand, BXLs with an unsubstituted phenyl ring showed the best stabilization effects of G-quadruplex. Circular dichroism spectroscopy results suggest mixed binding mode, groove binding and partial intercalation, to ds-DNA/RNA and end-stacking to top or bottom G-tetrads as the main binding modes of BXLs to those targets. All compounds exhibited micromolar binding affinities toward HSA and an increased protein thermal stability. Moderate to strong antiradical scavenging activity was observed for all BXLs with hydroxy groups at C-6, C-9 and C-10 positions of the benzoxanthene core, except for derivative bearing methoxy groups at these positions. BXLs with unsubstituted or low-substituted phenyl ring and one derivative without phenyl ring showed strong growth inhibition of Gram-positive Staphylococcus aureus. All compounds showed moderate to strong tumor cell growth-inhibitory activity and cytotoxicity.

Novel benzo[b]xanthene derivatives: Bismuth(III) triflate-catalyzed one-pot synthesis, characterization, and acetylcholinesterase, glutathione S-transferase, and butyrylcholinesterase inhibitory properties.

In this study, 3,4-dihydro-12-aryl-1H-benzo[b]xanthene-1,6,11-(2H,12H)trione compounds were obtained through one-pot condensation of various substituted aromatic aldehydes, 2-hydroxy-1,4-naphthoquinone, and dimedone in the presence of Bi(OTf)3 as a green and reusable catalyst. The structural characterization of these novel substituted benzo[b]xanthenes was performed by spectroscopic methods, and their inhibitory actions against butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and glutathione S-transferase (GST) were investigated. GST is an enzyme responsible for removing toxic molecules during Phase II reactions in the detoxification mechanism. The AChE and BChE enzymes, which are called cholinesterases, are among the enzymes that occur especially during dementia such as brain damage or Alzheimer's disease. Inhibition effects of the benzo[b]xanthene derivatives on AChE, BChE, and GST were found at the millimolar level. The best inhibitor for GST is compound 4a (31.18 ± 6.13 mM), for AChE, it is compound 4d (28.16 ± 3.46 mM), and for BChE, it is compound 4f (36.24 ± 3.19 mM). Compound 4a inhibited the dimerization of GST subunits, and compounds 4d and 4f directly inhibited the catalytic activity by interacting with the catalytic active site or a related site of the AChE and BChE enzymes, respectively.

Colorimetric Chemosensor and Turn on Fluorescence Probe for pH Monitoring Based on Xanthene Dye Derivatives and its Bioimaging of Living Escherichia coli Bacteria.

A new turn on fluorescence probe based on 3',6'-dihydroxy-6-methyl-2-((pyridin-2-ylmethylene)amino)-4-(p-tolyl)spiro[benzo[f]isoindole-1,9'-xanthen]-3(2H)-one (BFFPH) derived from benzo[f]fluorescein was prepared. Full characterization of the prepared probe using spectroscopic analysis was described such as IR, NMR and MS spectra. The sensitivity of BFFPH for monitoring of pH change in alkaline medium was studied. BFFPH exhibited a high sensitivity to alkaline pH by two pKa values at 8.82 and 10.66 in UV/vis spectroscopy titration. The pH monitoring was studied in broad range of pH values (2.5-12.2) at two pKa values at 8.72 and 10.73 by recording the effect of pH on the fluorescence intensity of BFFPH. The acid-base reversibility character of the probe was investigated as well as the effect of the pH change on the fluorescence quantum yield. The application of the prepared BFFPH probe for detection of living Escherichia coli (E. coli) bacteria using confocal fluorescence microscope was investigated.