Salicylaldehyde built fluorescent probe for dual sensing of Al3+, Zn2+ ions: Applications in latent fingerprint, bio-imaging & real sample analysis.

This Schiff base chemosensor (SNN) detected dual ions, Al3+ and Zn2+ ions selectively. Fluorescence spectrum investigations showed that Al3+ ions increased fluorescence intensity, notably at 493 nm. Introducing Zn2+ ions caused a significant blue shift of roughly ∼65 nm at a wavelength of 434 nm, resulting in a notable change in fluorescence intensity. When binding Al3+/Zn2+ ions, the SNN receptor uses three methods. Inhibition of photoinduced electron transfer (PET), excited state intramolecular proton transfer (ESIPT), and restriction of CN isomerization. The jobs plot method found that SNN + Al3+ and SNN + Zn2+ complexations had a 1:1 stoichiometry. DFT, LC-HRMS, and 1H NMR titration confirm this conclusion. The probe SNN's limit of detection (LOD) for Al3+/Zn2+ ions was 3.99 nM and 1.33 nM. Latent fingerprint (LFP), food samples, pharmaceutical products, and E. coli pathogen bio-imaging have all used the SNN probe to identify Al3+ and Zn2+ ions.

In-vitro investigation on the biological activities of squalene derived from the soil fungus Talaromyces pinophilus.

The consistent increase in multidrug resistance among pathogens and increased cancer incidence are serious public health concerns and threaten humans by killing countless lives. In the present study, Talaromyces pinophilus CJ15 was characterized and evaluated for its antibacterial, candidicidal and cytotoxic activities. The selected isolate Talaromyces pinophilus CJ15 with 18S rRNA gene sequence of 1021 base pairs exhibited antifungal activity on plant pathogens via dual culture. The GC-MS profiling of crude extract illustrated the existence of many bioactive macromolecules which include squalene belonging to the terpenoids family. The biological macromolecules in the bioactive fraction of CJ15 exhibited increasing antibacterial activity with an increase in concentration such that the highest activity was recorded against Shigella flexneri with 15, 18, 20, and 24 mm inhibition zones at 25, 50, 75 and 100 µl concentrations, respectively. The squalene, having a molecular weight of 410.718 g/mol, displayed candidicidal activity with a right-side shifted log phase in the growth curve of all the treated Candida species, indicating delayed exponential growth. In cytotoxic activity, the extracted squalene exhibited an IC50 concentration of 26.22 µg/ml against JURKAT cells and induced apoptosis-induced cell death. This study's outcomes encourage the researchers to explore further the development of new and improved bioactive macromolecules that could help to prevent infections and human blood cancer.

An eco-friendly ultrasound approach to extracting yellow dye from Cassia alata flower petals: Characterization, dyeing, and antibacterial properties.

Using natural dyes in dyeing industries becomes an alternative to synthetic dyes, which are known to contain harmful chemicals that can pose risks to the environment and human health. This study involves the extraction of yellow dye from Cassia alata flower petals, optimization of the extraction process using an ultrasonic bath (40 KHz and an input power of 500), ultrasonic probe (390 W, 455 W, 520 W, 585 W, and 650 W), and conventional heating (heating mantle with 30 °C, 40 °C, 50 °C, 60 °C, and 70 °C), characterization of the dye, as well as dyeing (cotton, silk, and leather) without using a mordant. The extracted yellow dye was further evaluated to determine its antibacterial activity against skin bacteria. Dye extraction optimization using UV-Visible spectrophotometric analysis revealed that the maximum yellow color in methanol extract (287 and 479 nm) was obtained at 50 °C for 45 min using ultrasonic water bath extraction, followed by the ultrasonic probe and direct heating. Based on the FTIR spectra, it is evident that OH is present at approximately 3300 cm-1, while CH stretches at around 2900 cm-1. A characteristic peak at 1608 cm-1 bears a striking similarity to anthraquinonoid-based compounds. Also, using the ultrasonic water bath dyeing technique at 50 °C for 45 min, the yellow color of cotton, silk, and leather was dyed optimally. Due to effective color removal after two washings with boiling soap liquid, the dyed cotton and silk fabric displayed good washing and rubbing fastness. Regarding antibacterial activity, the dye was highly active against all pathogens after extraction in methanol. The maximum inhibition was observed against Pseudomonas sp. with a MIC value of 1.56 mg/ml.

A lead selective dimeric quinoline based fluorescent chemosensor and its applications in milk and honey samples, smartphone and bio-imaging.

Dimeric quinoline-based Schiff base was developed (DQS) for the specific detection of Pb2+ ion via fluorimetry. DQS coordinates with Pb2+, a variation in fluorescence intensity with enhanced radical blue shift was observed due to the restriction of CN rotation, CN isomerization, and photoinduced electron transfer (PET) mechanisms. In addition, the intramolecular charge transfer (ICT) from electron-donating morpholine to phenylene diamine acceptor linked quinoline bridge is responsible for the blue-shifted fluorescence enhancement in the DQS-Pb2+ complex. The binding stoichiometry of DQS: Pb2+ (1:2) was confirmed by host-guest titration and mass spectrometry. The limit of detection (LOD) of the DQS was found to be 1.3 × 10-7 M for Pb2+ ion. The DQS sensing ability of Pb2+ was further applied into milk and honey samples, smartphone, bio-imaging and to construct of an INHIBIT molecular logic gate.

Antimicrobial activities of spirooxindolopyrrolidine tethered dicarbonitrile heterocycles against multidrug resistant nosocomial pathogens.

BACKGROUND: Microbial infections together with rising drug resistance pose a threat to immunocompromised individual. In this perspective, compounds with spirooxindolopyrrolidine play a significant role in research on antimicrobial drug delivery research owing to their various pharmaceutical activities. Spiroheterocyclic compounds are present in number of medications as active motif due to their exceptional structural properties which enable for easy interaction with the protein of the biological target. Inspired by this biological precedent encouraged to synthesize a new class of dispirooxindole fused pyrrolidine heterocycles via a three-component cycloaddition strategy. MATERIALS AND METHODS: The new class of structurally intriguing spirooxindolopyrrolidines were synthesized through three component cycloaddition process and the structure of products were assigned through spectroscopic analysis. The newly synthesized compounds were assessed for their antimicrobial sensitivity test with standard Kirby Bauer method with common drugs. RESULTS: The structurally unexplored hybrid heterocycles fused spirooxindolopyrrolidine exhibited excellent antimicrobial activity against the common nosocomial microbial pathogens. Of four compounds, the compound bearing a chlorine atom on the aryl ring (4a) exhibited significant antimicrobial activity (zone of inhibition: 9.00 ± 1.00-17.00 ± 0.35 mm and MIC: 16.00-256.00 µg/mL) against selected nosocomial infection causing microbial pathogens. Hence, the compound 4a has been considered as an effective drug of interest in therapeutic field for compacting infectious diseases causing pathogens. CONCLUSION: With an aim of developing more effective and economically more affordable antimicrobial leads with a unique mechanism of action, we have designed and synthesized structurally diverse spirooxindolopyrrolidine tethered hybrids that has been assayed against multidrug resistant nosocomial pathogens. The regioisomer having chloro substituted on the phenyl ring showed potent activity when compared to standard drug. Future studies are required to explicate the pharmacological properties of new hybrid heterocycles that have been synthesized in our laboratory for the novel therapeutic development.

Dispiropyrrolidine tethered piperidone heterocyclic hybrids with broad-spectrum antifungal activity against Candida albicans and Cryptococcus neoformans.

Invasive fungal infections along with rising incidence of resistance to antifungal drugs pose increasing threat to immunocompromised individuals, including cancer patients. In this study, we examined the antifungal activity of dispiropyrrolidine tethered piperidone heterocyclic hybrids. Results indicate that compounds 5a and 6i have demonstrated a potent antifungal effect on multiple fungal strains, including Candida albicans, without exhibiting cytotoxicity to mammalian cells. Furthermore, these two compounds exhibited significant inhibition on Candida albicans hyphae and biofilm development that surpasses the FDA-approved antifungal drug currently used for treatment. Taken together, our results suggest that 5a and 6i are promising candidates for development into new antifungal drugs.

Anti-tubercular activity of novel class of spiropyrrolidine tethered indenoquinoxaline heterocyclic hybrids.

A series of structurally intriguing novel class of spiropyrrolidine tethered quinoxaline heterocyclic hybrids has been achieved in excellent yields employing ionic liquid accelerated multicomponent 1,3-dipolar cycloaddition reaction strategy. ß-Nitrostyrenes were used as dipolarophiles, while the 1,3-dipole component was the azomemthine ylide, generated in situ from indenoquinoxaline and l-phenylalanine. The reaction provided three new bonds and four contiguous stereocenter with full distereomeric control. In vitro activity of these spiroheterocyclic hybrids against Mycobacterium tuberculosis H37Rv using MABA assay revealed that the compound with nitro group on the phenyl ring is the most active candidate (1.56 µg/mL) among the other analogues of the series and has an activity similar to that of the standard drug, Ethambutol.

Broad-spectrum antifungal activity of spirooxindolo-pyrrolidine tethered indole/imidazole hybrid heterocycles against fungal pathogens.

Invasive fungal infections are one of the leading causes of nosocomial bloodstream infections with a limited treatment option. A series of derivatized spirooxindolo-pyrrolidine tethered indole and imidazole heterocyclic hybrids have been synthesized, and their antifungal activity against fungal strains were determined. Here we characterize the antifungal activity of a specific spirooxindolo-pyrrolidine hybrid, dubbed compound 9c, a spirooxindolo-pyrrolidine tethered imidazole synthesized with a 2-chloro and trifluoromethoxy substituent. The compound 9c exhibited no cytotoxicity against mammalian cell line at concentrations that inhibited fungal strains. Compound 9c also significantly inhibited the fungal hyphae and biofilm formation. Our results indicate that spirooxindolo-pyrrolidine heterocyclic hybrids potentially represent a broad class of chemical agents with promising antifungal potential.

Domino Multicomponent Approach for the Synthesis of Functionalized Spiro-Indeno[1,2-b]quinoxaline Heterocyclic Hybrids and Their Antimicrobial Activity, Synergistic Effect and Molecular Docking Simulation.

An expedient synthesis of hitherto unexplored novel hybrid heterocycles comprising dispiropyrrolidine, N-styrylpiperidone and indeno[1,2-b]quinoxaline units has been developed via domino multicomponent 1,3-dipolar cycloaddition strategy employing a new class of azomethine ylide in ionic liquid, 1-butyl-3-methylimidazolium bromide. This domino protocol involves, 1,3-dipolar cycloaddition and concomitant enamine reaction affording the dispiropyrrolidine tethered N-styrylpiperidone hybrid heterocycles in moderate to good yield in a single step. These compounds were evaluated for their antimicrobial activity against bacterial and fungal pathogens, therein compounds 8f, 8h, and 8l displayed significant activity against tested microbial pathogens. The synergistic effect revealed that the combination of compound 8h with streptomycin and vancomycin exhibited potent synergistic activity against E. coli ATCC 25922. In addition, molecular docking simulation has also been studied for the most active compound.

Glucosamine-6-phosphate synthase inhibiting C3-ß-cholesterol tethered spiro heterocyclic conjugates: Synthesis and their insight of DFT and docking study.

A series of novel covalent cholesterol-spiro pyrrolidine/pyrrolizidine heterocyclic hybrids possessing biologically active oxindole, indanedione, and acenaphthylene-1-one have been synthesized by the reaction of C3-ß-cholesteroalacrylate with heterocyclic di- and tri-ketones. All the sixteen compounds were obtained as a single isomer in good yield through a stereo- and regio- selective 1,3-dipolar cycloaddition methodology. Stereochemistry of the spiranic cycloadducts has been established by spectroscopic analysis and the regioselectivity outcome of the spiro adducts has been accomplished by DFT calculations at B3LYP/6-31G (d,p) level study. In vitro antibacterial activity of the newly synthesized cycloadducts were evaluated against highly pathogenic Gram-positive and Gram-negative bacteria and the most active compounds 5a, 13, and 14 underwent automated in silico molecular docking analysis in order to validate their effective orientation as a inhibitors bound in the active site of glucosamine-6-phosphate synthase (1XFF) enzyme by employing AutoDock Tools.

Benzimidazole tethered pyrrolo[3,4-b]quinoline with broad-spectrum activity against fungal pathogens.

Fungal infections caused by Candida and Cryptococcus are particularly dangerous for immunocompromised individuals. In this study, we identified that benzimidazole fused pyrrolo[3,4-b]quinoline compounds have potent antifungal activity against several clinical isolates of pathogenic fungal strains. Specifically, the compound 6a did not show cytotoxicity against mammalian cells at a concentration that inhibits the growth of fungal strains. In addition, the compound 6a also significantly reduced the metabolic activity of fungal cells in the Candida albicans biofilms. Collectively, our results indicate that benzimidazole fused quinoline compounds have a potential to develop as an antifungal agents.

Synthesis of indole-cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process.

The one-pot four-component reaction of 3-(1H-indol-3-yl)-3-oxopropanenitriles, aromatic aldehydes, cycloalkanones and ammonium acetate occurred via a six-step tandem Knoevenagel condensation-nucleophilic addition to carbonyl-Michael addition-N-cyclization-elimination-air oxidation sequence to afford structurally intriguing indole-cycloalkyl[b]pyridine-3-carbonitrile hybrid heterocycles in excellent yields.

Spiropyrrolidine/spiroindolizino[6,7-b]indole heterocyclic hybrids: Stereoselective synthesis, cholinesterase inhibitory activity and their molecular docking study.

A regio and stereo- selective synthesis of hitherto unexplored hybrid heterocyclic system comprising spiropyrrolidine, indolizino[6,7-b]indole units in good to excellent yields, has been developed via three component 1,3-dipolar cycloaddition and concomitant trifluoroacetic acid catalyzed Pictet-Spengler cyclization with paraformaldehyde. The newly synthesized compounds were evaluated for their in vitro acetylcholinesterase (AChE) and butylcholinesterase (BChE) enzyme inhibitory activities. Most of the synthesized compounds showed good inhibitory activity, among them, compounds 4d and 4g displayed highest potency against AChE (IC50 1.88 and 1.98 µM), and BChE (IC50 18.32 and 10.21 µM) enzyme, respectively than the standard drug, galanthamine. Molecular modeling simulation was investigated for the most active compounds 4d and 4g on AChE and BChE enzymes to disclose the binding and orientation of these molecules into active site of respective receptors.

Multicomponent Domino Synthesis, Anticancer Activity and Molecular Modeling Simulation of Complex Dispirooxindolopyrrolidines.

A series of spirooxindolopyrrolidine fused N-styrylpiperidone heterocyclic hybrids has been synthesized in excellent yield via a domino multicomponent protocol that involves one-pot three component 1,3-dipolar cycloaddition and concomitant enamine reactions performed in an inexpensive ionic liquid, namely 1-butyl-3-methylimidazolium bromide ([bmim]Br). Compounds thus synthesized were evaluated for their cytotoxicity against U-937 tumor cells. Interestingly; compounds 5i and 5m exhibited a better cytotoxicity than the anticancer drug bleomycin. In addition; the effect of the synthesized compounds on the nuclear morphology of U937 FaDu cells revealed that treatment with compounds 5a⁻m led to their apoptotic cell death.

Design, synthesis and antiproliferative activity of decarbonyl luotonin analogues.

A small library of benzimidazole-fused pyrrolo[3,4-b]quinoline has been synthesized from readily available benzimidazole 2-carbaldehyde and various substituted arylamines in good to excellent yields utilizing an intramolecular Povarov reaction catalyzed by boron trifluoride diethyl etharate as the key final step. The compounds thus synthesized can be considered as decarbonyl analogues of the anticancer alkaloid luotonin A and were evaluated in a DNA relaxation assay for their ability to inhibit human topoisomerase I. Interestingly, two of the compounds showed a remarkable activity that is comparable to that of the standard drug camptothecin. The compounds were also evaluated for their cytotoxic effect in four highly aggressive human cancer cell lines, namely KB, MDA-MB231 (breast), LNCap (prostate), and HT1080 (fibrosarcoma). Some of the compounds obtained showed promising cytotoxicities for these four cell lines.

A One-Pot Multicomponent 1,3-Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Dihydrothiophenone-Engrafted Dispiro Hybrid Heterocycles.

The combinatorial syntheses of a library of novel dihydrothiophenone-engrafted dispiro oxindole/indenoquinoxaline-pyrrolidine/pyrrolothiazole/indolizine hybrid heterocycles have been realized through a chemo-, regio-, and stereoselective multicomponent 1,3-dipolar cycloaddition strategy.

Synthesis, Spectroscopic, X-ray Diffraction and DFT Studies of Novel Benzimidazole Fused-1,4-Oxazepines.

A series of benzimidazole-tethered oxazepine heterocyclic hybrids has been synthesized in good to excellent yields from an N-alkylated benzimidazole 2-carboxaldehyde, which in turn was accomplished from o-phenylenediamine in three good yielding steps. The calculated molecular structure of compounds 2-methyl-4-(2-((phenylimino)methyl)-1H-benzo-[d]imidazol-1-yl)-butan-2-ol 9 and 10 3,3-dimethyl-N-phenyl-1,2,3,5-tetrahydrobenzo-[4,5]imidazo[2,1-c][1,4]oxazepin-5-amine using the B3LYP/6-31 G(d, p) method were found to agree well with their X-ray structures. The charge distributions at the different atomic sites were computed using the natural bond orbital (NBO) method. The regions of electrophilic and nucleophilic reactivity were shown using a molecular electrostatic potential (MEP) map. In addition, the frontier molecular orbitals of these compounds were discussed at the same level of theory. Nonlinear optical (NLO) properties have also been investigated by computational hyperpolarizability studies, and it was found that Compound 9 is the best candidate for NLO applications.

Multicomponent Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Novel Spiro-Tethered Pyrazolo[3,4-b]quinoline Hybrid Heterocycles.

The stereoselective syntheses of a library of novel spiro-tethered pyrazolo[3,4-b]quinoline-pyrrolidine/pyrrolothiazole/indolizine-oxindole/acenaphthene hybrid heterocycles have been achieved through the 1,3-dipolar cycloaddition of azomethine ylides generated in situ from α-amino acids and 1,2-diketones to dipolarophiles derived from pyrazolo[3,4-b]quinoline derivatives.

A Sustainable Approach to the Stereoselective Synthesis of Diazaheptacyclic Cage Systems Based on a Multicomponent Strategy in an Ionic Liquid.

The microwave-assisted three-component reactions of 3,5-bis(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones, acenaphthenequinone and cyclic α-amino acids in an ionic liquid, 1-butyl-3-methylimidazolium bromide, occurred through a domino sequence affording structurally intriguing diazaheptacyclic cage-like compounds in excellent yields.

Synthesis and discovery of highly functionalized mono- and bis-spiro-pyrrolidines as potent cholinesterase enzyme inhibitors.

Novel mono and bis spiropyrrolidine derivatives were synthesized via an efficient ionic liquid mediated, 1,3-dipolar cycloaddition methodology and evaluated in vitro for their AChE and BChE inhibitory activities in search for potent cholinesterase enzyme inhibitors. Most of the synthesized compounds displayed remarkable AChE inhibitory activities with IC50 values ranging from 1.68 to 21.85 µM, wherein compounds 8d and 8j were found to be most active inhibitors against AChE and BChE with IC50 values of 1.68 and 2.75 µM, respectively. Molecular modeling simulation on Torpedo californica AChE and human BChE receptors, showed good correlation between IC50 values and binding interaction template of the most active inhibitors docked into the active site of their relevant enzymes.