A spectroscopy based prototype for the noninvasive detection of diabetes from human saliva using nanohybrids acting as nanozyme.

The recent prediction of diabetes to be a global pandemic invites a detection strategy preferably non-invasive, and bloodless to manage the disease and the associated complications. Here, we have synthesized chitosan polymer functionalized, organic-inorganic bio-compatible nano-hybrids of Mn3O4 nanoparticles, and characterized it by utilizing several optical methodologies for the structural characterization which shows the Michaelis Menten (MM) kinetics for glucose and alpha-amylase protein (well-known diabetes biomarkers). We have also studied the potentiality for the detection of alpha-amylase in human salivary secretion which is reported to be strongly correlated with uncontrolled hyperglycemia. Finally, we have developed a prototype for the measurement of glucose (LOD of 0.38 mg/dL, LOQ of 1.15 mg/dL) and HbA1c (LOD of 0.15% and LOQ of 0.45%) utilizing the basic knowledge in the study for the detection of uncontrolled hyperglycemia at the point-of-care. With the limited number of clinical trials, we have explored the potential of our work in combating the diabetic pandemic across the globe in near future.

Investigation of photophysical and electronic properties of aurone derivatives: Insights from spectroscopic techniques and density functional theory calculations.

This paper reports on a study of the photophysical properties, density functional theory (DFT) calculations, infrared (IR), ultraviolet (UV) and nuclear magnetic resonance (NMR) spectroscopic techniques of a series of aurone compounds. The photophysical properties were investigated using UV absorption and fluorescence spectroscopy in a dimethyl sulfoxide (DMSO) solution. Furthermore, the fluorescence quantum yields of the target compounds (1-24) were also investigated. Remarkably, these compounds revealed high quantum yields (Φ = 0.001-0.729) as compared to the already existing aurones in literature. The DFT calculations were performed to elucidate the electronic structure, energy levels and draw a comparison between experimental and theoretical findings. The simulated properties such as molecular frontier orbitals, the density of states, reactivity descriptors (GCRD), electrostatic potential distribution, transition density matrix, electron localization function (ELF) and localized orbital locator (LOL) have been calculated using DFT. The DFT calculations provided insight into the electronic structure and energy levels of the aurone compounds, while the IR and UV spectroscopy results shed light on their functional groups and electronic transitions, respectively. The results of this study contribute to a better understanding of the photophysical properties of aurone compounds and suggest their potential use in technological applications.

First Exclusive Stereo- and Regioselective Preparation of 5-Arylimino-1,3,4-Selenadiazole Derivatives: Synthesis, NMR analysis, and Computational Studies.

Isoselenocyanates are valuable coupling partners required for preparing key chemical intermediates and biologically active molecules in an accelerated and effective way. Likewise, (Z)-2-oxo-N-phenylpropanehydrazonoyl chlorides have been employed in numerous one-step heteroannulation reactions to assemble the structural core of several various kinds of heterocyclic compounds. Here, we describe the inverse electron demand 1,3-dipolar cycloaddition reaction of isoselenocyanates with a variety of substituted (Z)-2-oxo-N-phenylpropanehydrazonoyl chlorides to generate, regioselectively and stereoselectively, a series of 5-arylimino-1,3,4-selenadiazole derivatives comprising a multitude of functional groups on both aryl rings. The synthetic method features gentle room-temperature conditions, wide substrate scope, and good to high reaction yields. The selenadiazoles were separated by gravity filtration in all instances and chemical structures were validated by multinuclear NMR spectroscopy and high accuracy mass spectral measurements. First conclusive molecular structure elucidation of the observed 5-arylimino-selenadiazole regioisomer was verified by single-crystal X-ray diffraction analysis. Crystal-structure measurement was successfully carried out on (Z)-1-(4-(4-iodophenyl)-5-(p-tolylimino)-4,5-dihydro-1,3,4-selenadiazol-2-yl)ethan-1-one and (Z)-1-(5-((4-methoxyphenyl)imino)-4-(4-(methylthio)phenyl)-4,5-dihydro-1,3,4-selenadiazol-2-yl)ethan-1-one. Likewise, the (Z)-geometry of the hydrazonoyl chloride reactant was proven by X-ray diffraction studies. As representative examples, crystal-structure determination was carried out on (Z)-2-oxo-N-phenylpropanehydrazonoyl chloride and (Z)-N-(3,5-bis(trifluoromethyl)phenyl)-2-oxopropanehydrazonoyl chloride. Density functional theory calculations at the B3LYP-D4/def2-TZVP level were conducted to support the noted experimental findings and suggested mechanism.

Current status of N-, O-, S-heterocycles as potential alkaline phosphatase inhibitors: a medicinal chemistry overview.

Heterocycles are a class of compounds that have been found to be potent inhibitors of alkaline phosphatase (AP), an enzyme that plays a critical role in various physiological processes such as bone metabolism, cell growth and differentiation, and has been linked to several diseases such as cancer and osteoporosis. AP is a widely distributed enzyme, and its inhibition has been considered as a therapeutic strategy for the treatment of these diseases. Heterocyclic compounds have been found to inhibit AP by binding to the active site of the enzyme, thereby inhibiting its activity. Heterocyclic compounds such as imidazoles, pyrazoles, and pyridines have been found to be potent AP inhibitors and have been studied as potential therapeutics for the treatment of cancer, osteoporosis, and other diseases. However, the development of more potent and selective inhibitors that can be used as therapeutics for the treatment of various diseases is an ongoing area of research. Additionally, the study of the mechanism of action of heterocyclic AP inhibitors is an ongoing area of research, which could lead to the identification of new targets and new therapeutic strategies. The enzyme known as AP has various physiological functions and is present in multiple tissues and organs throughout the body. This article presents an overview of the different types of AP isoforms, their distribution, and physiological roles. It also discusses the structure and mechanism of AP, including the hydrolysis of phosphate groups. Furthermore, the importance of AP as a clinical marker for liver disease, bone disorders, and cancer is emphasized, as well as its use in the diagnosis of rare inherited disorders such as hypophosphatasia. The potential therapeutic applications of AP inhibitors for different diseases are also explored. The objective of this literature review is to examine the function of alkaline phosphatase in various physiological conditions and diseases, as well as analyze the structure-activity relationships of recently reported inhibitors. The present review summarizes the structure-activity relationship (SAR) of various heterocyclic compounds as AP inhibitors. The SAR studies of these compounds have revealed that the presence of a heterocyclic ring, particularly a pyridine, pyrimidine, or pyrazole ring, in the molecule is essential for inhibitory activity. Additionally, the substitution pattern and stereochemistry of the heterocyclic ring also play a crucial role in determining the potency of the inhibitor.

Evaluation of 2,3-Dihydro-1,5-benzothiazepine Derivatives as Potential Tyrosinase Inhibitors: In Vitro and In Silico Studies.

Benzothiazepines are pharmacologically active compounds, frequently utilized as a precursor for acquiring versatile molecules with several bioactivities including anti-inflammatory, anti-human immunodeficiency virus (anti-HIV), analgesic, antitumor, antimicrobial, and antitubercular. In this study, the 2,4-diphenyl-2,3-dihydro-1,5-benzothiazepine scaffold was selected for their in vitro, docking, and druglikeness studies to evaluate their inhibitory potential against mushroom tyrosinase. All synthesized analogues, 1-14, exhibited moderate to good IC50 values ranging from 1.21 to 70.65 µM. The synthesized benzothiazepine derivatives were potent tyrosinase inhibitors, which outperformed the reference kojic acid (IC50 = 16.69 µM). The kinetic analysis revealed that compound 2 (2-(3,4-dimethoxyphenyl)-4-(p-tolyl)-2,3-dihydrobenzo[b][1,4]thiazepine) was a mixed-type tyrosinase inhibitor with a Ki value of 1.01 µM. Molecular modeling studies against tyrosinase protein (PDB ID: 2Y9X) were conducted to recognize the binding modes of these analogues. The utilization of molecular dynamic (MD) simulations enabled the assessment of the protein-ligand complex's dynamic behavior, stability, and binding affinity for the compounds. These simulations ultimately led to the identification of compound 2 as a potential inhibitor of tyrosinase. Additionally, a druglikeness study was conducted, which supported the promising potential of the new analogues as novel antityrosinase agents. The in silico studies were consistent with the in vitro results, showing that these ligands had good binding scores against tyrosinase and interacted with the core residues of the target protein. Gaussian 09 was used for the geometry optimization of all complexes.

Novel Indole-Tethered Chromene Derivatives: Synthesis, Cytotoxic Properties, and Key Computational Insights.

Indole-tethered chromene derivatives were synthesised in a one-pot multicomponent reaction using N-alkyl-1H-indole-3-carbaldehydes, 5,5-dimethylcyclohexane-1,3-dione, and malononitrile, catalysed by DBU at 60-65 °C in a short reaction time. The benefits of the methodology include non-toxicity, an uncomplicated set-up procedure, a faster reaction time, and high yields. Moreover, the anticancer properties of the synthesised compounds were tested against selected cancer cell lines. The derivatives 4c and 4d displayed very good cytotoxic activity, with IC50 values ranging from 7.9 to 9.1 µM. Molecular docking revealed the potent derivatives have good binding affinity towards tubulin protein, better than the control, and the molecular dynamic simulations further demonstrated the stability of ligand-receptor interactions. Moreover, the derivatives followed all the drug-likeness filters.

Inhibitory potential of nitrogen, oxygen and sulfur containing heterocyclic scaffolds against acetylcholinesterase and butyrylcholinesterase.

Heterocycles are the key structures in organic chemistry owing to their immense applications in the biological, chemical, and pharmaceutical fields. Heterocyclic compounds perform various noteworthy functions in nature, medication, innovation etc. Most frequently, pure nitrogen heterocycles or various positional combinations of nitrogen, oxygen, and sulfur atoms in five or six-membered rings can be found. Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes is a popular strategy for the management of numerous mental diseases. In this context, cholinesterase inhibitors are utilized to relieve the symptoms of neurological illnesses like dementia and Alzheimer's disease (AD). The present review focuses on various heterocyclic scaffolds and their role in designing and developing new potential AChE and BChE inhibitors to treat AD. Moreover, a detailed structure-activity relationship (SAR) has been established for the future discovery of novel drugs for the treatment of AD. Most of the heterocyclic motifs have been used in the design of new potent cholinesterase inhibitors. In this regard, this review is an endeavor to summarize the biological and chemical studies over the past decade (2010-2022) describing the pursuit of new N, O and S containing heterocycles which can offer a rich supply of promising AChE and BChE inhibitory activities.

High-Efficacy Hierarchical Dy2O3/TiO2 Nanoflower toward Wastewater Reclamation: A Combined Photoelectrochemical and Photocatalytic Strategy.

Developing a sustainable photocatalyst is crucial to mitigate the foreseeable energy shortage and environmental pollution caused by the rapid advancement of global industry. We developed Dy2O3/TiO2 nanoflower (TNF) with a hierarchical nanoflower structure and a near-ideal anatase crystallite morphology to degrade aqueous rhodamine B solution under simulated solar light irradiation. The prepared photocatalyst was well-characterized using powder X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, energy-dispersive spectroscopy, scanning electron microscopy, Brunauer-Emmett-Teller, diffuse reflectance UV-vis spectra, and X-ray photoelectron spectroscopy. Further analysis was performed to highlight the photoelectrochemical activity of the prepared photocatalysts such as electrochemical impedance spectroscopy, linear sweep voltammetry, photocurrent response, and a Mott-Schottky study. The crystalline Dy2O3/TNF exhibits superb photocatalytic activity attributed to the improved charge transfer, reduced recombination rate of the electron-hole pairs, and a remarkable red-shift in light absorption.

Novel Pyran-Linked Phthalazinone-Pyrazole Hybrids: Synthesis, Cytotoxicity Evaluation, Molecular Modeling, and Descriptor Studies.

A series of novel pyran-linked phthalazinone-pyrazole hybrids were designed and synthesized by a facile one-pot three-component reaction employing substituted phthalazinone, 1H-pyrazole-5-carbaldehyde, and active methylene compounds. Optimization studies led to the identification of L-proline and ethanol as efficient catalyst and solvent, respectively. This was followed by evaluation of anticancer activity against solid tumor cell lines of lung and cervical carcinoma that displayed IC50 values in the range of 9.8-41.6 µM. Molecular modeling studies were performed, and crucial interactions with the target protein were identified. The drug likeliness nature of the compounds and molecular descriptors such as molecular flexibility, complexity, and shape index were also calculated to understand the potential of the synthesized molecules to act as lead-like molecule upon further detailed biological investigations as well as 3D-QSAR studies.

Scholl reaction as a powerful tool for the synthesis of nanographenes: a systematic review.

Nanographenes, or extended polycyclic aromatic hydrocarbons, have been attracting increasing attention owing to their widespread applications in organic electronics. However, the atomically precise fabrication of nanographenes has thus far been achieved only through synthetic organic chemistry. Polycyclic aromatic hydrocarbons (PAHs) are popular research subjects due to their high stability, rigid planar structure, and characteristic optical spectra. The recent discovery of graphene, which can be regarded as giant PAH, has further stimulated research interest in this area. Chemists working with nanographene and heterocyclic analogs thereof have chosen it as their preferred tool for the assembly of large and complex architectures. The Scholl reaction has maintained significant relevance in contemporary organic synthesis with many advances in recent years and now ranks among the most useful C-C bond-forming processes for the generation of the π-conjugated frameworks of nanographene or their heterocyclic analogs. A broad range of oxidants and Lewis acids have found use in Scholl-type processes, including Cu(OTf)2/AlCl3, FeCl3, MoCl5, PIFA/BF3-Et2O, and DDQ, in combination with Brønsted or Lewis acids, and the surface-mediated reaction has found especially wide applications in PAH synthesis. Undoubtedly, the utility of the Scholl reaction is supreme in the construction of nanographene and their heterocyclic analogues. The detailed analysis of the progress achieved in this field reveals that many groups have contributed by pushing the boundary of structural possibilities, expanding into surface-assisted cyclodehydrogenation and developing new reagents. In this review, we highlight and discuss the recent modifications in the Scholl reaction for nanographene synthesis using numerous oxidant systems. In addition, the merits or demerits of each oxidative reagent is described herein.

New Imidazole-Based N-Phenylbenzamide Derivatives as Potential Anticancer Agents: Key Computational Insights.

An efficient atom-economical synthetic protocol to access new imidazole-based N-phenylbenzamide derivatives is described. A one-pot three-component reaction was utilized to provide a series of N-phenylbenzamide derivatives in a short reaction time (2-4 h) with an 80-85% yield. The cytotoxic evaluation revealed that derivatives 4e and 4f exhibited good activity, with IC50 values between 7.5 and 11.1 µM against the tested cancer cell lines. Computational studies revealed interesting insights: the docking of the active derivatives (4e and 4f) showed a higher affinity toward the target receptor protein than the control. Molecular dynamic simulations revealed that the active derivatives form stable complexes with the ABL1 kinase protein. Moreover, the ADME and drug-likeness of the derivatives reinforced the potential of the derivatives to be taken up for further development as anticancer agents.

Natural and synthetic flavonoid derivatives as new potential tyrosinase inhibitors: a systematic review.

Tyrosinase is a multifunctional glycosylated and copper-containing oxidase that is highly prevalent in plants and animals and plays a pivotal role in catalyzing the two key steps of melanogenesis: tyrosine's hydroxylation to dihydroxyphenylalanine (DOPA), and oxidation of the latter species to dopaquinone. Melanin guards against the destructive effects of ultraviolet radiation which is known to produce considerable pathological disorders such as skin cancer, among others. Moreover, the overproduction of melanin can create aesthetic problems along with serious disorders linked to hyperpigmented spots or patches on skin. Several skin-whitening products which reduce melanogenesis activity and alleviate hyperpigmentation are commercially available. A few of them, particularly those obtained from natural sources and that incorporate a phenolic scaffold, have been exploited in the cosmetic industry. In this context, synthetic tyrosinase inhibitors (TIs) with elevated efficacy and fewer side effects are direly needed in the pharmaceutical and cosmetic industries owing to their protective effect against pigmentation and dermatological disorders. Furthermore, the biological significance of the chromone skeleton and its associated medicinal and bioactive properties has drawn immense interest and inspired many researchers to design and develop novel anti-tyrosinase agents based on the flavonoid core (2-arylchromone). This review article is oriented to provide an insight and a deeper understanding of the tyrosinase inhibitory activity of an array of natural and bioinspired phenolic compounds with special emphasis on flavonoids to demonstrate how the position of ring substituents and their interaction with tyrosinase could be correlated with their effectiveness or lack thereof against inhibiting the enzyme.

Journey of anthraquinones as anticancer agents - a systematic review of recent literature.

Anthraquinones are privileged chemical scaffolds that have been used for centuries in various therapeutic applications. The anthraquinone moiety forms the core of various anticancer agents. However, the emergence of drug-resistant cancers warrants the development of new anticancer agents. The research endeavours towards new anthraquinone-based compounds are increasing rapidly in recent years. They are used as a core chemical template to achieve structural modifications, resulting in the development of new anthraquinone-based compounds as promising anticancer agents. Mechanistically, most of the anthraquinone-based compounds inhibit cancer progression by targeting essential cellular proteins. Herein, we review new anthraquinone analogues that have been developed in recent years as anticancer agents. This includes a systematic review of the recent literature (2005-2021) on anthraquinone-based compounds in cell-based models and key target proteins such as kinases, topoisomerases, telomerases, matrix metalloproteinases and G-quadruplexes involved in the viability of cancer cells. In addition to this, the developments in PEG-based delivery of anthraquinones and the toxicity aspects of anthraquinone derivatives are also discussed. The review dispenses a compact background knowledge to understanding anthraquinones for future research on the expansion of anticancer therapeutics.

2-Benzylidenebenzofuran-3(2H)-ones as a new class of alkaline phosphatase inhibitors: synthesis, SAR analysis, enzyme inhibitory kinetics and computational studies.

The excelling role of organic chemistry in the medicinal field continues to be one of the main leads in the drug development process. Particularly, this industry requires organic chemists to discover small molecular structures with powerful pharmacological potential. Herein, a diverse range of chalcone (1-11) and aurone (12-22) derivatives was designed and synthesized and for the first time, and both motifs were evaluated as potent inhibitors of alkaline phosphatases (APs). Structural identification of the target compounds (1-22) was accomplished using common spectroscopic techniques. The effect of the nature and position of the substituent was interestingly observed and justified based on the detailed structure-activity relationship (SAR) of the target compounds against AP. It was concluded from the obtained results that all the newly synthesized compounds exhibit high inhibitory potential against the AP enzyme. Among them, compounds 12 (IC50 = 2.163 ± 0.048 µM), 15 (IC50 = 2.146 ± 0.056 µM), 16 (IC50 = 2.132 ± 0.034 µM), 18 (IC50 = 1.154 ± 0.043 µM), 20 (IC50 = 1.055 ± 0.029 µM) and 21 (IC50 = 2.326 ± 0.059 µM) exhibited excellent inhibitory activity against AP, and even better/more active than KH2PO4 (standard) (IC50 = 2.80 ± 0.065 µM). Remarkably, compound 20 (IC50 = 1.055 ± 0.029 µM) may serve as a lead structure to design more potent inhibitors of alkaline phosphatase. To the best of our knowledge, these synthetic compounds are the most potent AP inhibitors with minimum IC50 values reported to date. Furthermore, a molecular modeling study was performed against the AP enzyme (1EW2) to check the binding interaction of the synthesized compounds 1-22 against the target protein. The Lineweaver-Burk plots demonstrated that most potential derivative 20 inhibited h-IAP via a non-competitive pathway. Finally, molecular dynamic (MD) simulations were performed to evaluate the dynamic behavior, stability of the protein-ligand complex, and binding affinity of the compounds, resulting in the identification of compound 20 as a potential inhibitor of AP. Accordingly, excellent correlation was observed between the experimental and theoretical results. The pharmacological studies revealed that the synthesized analogs 1-22 obey Lipinski's rule. The assessment of the ADMET parameters showed that these compounds possess considerable lead-like characteristics with low toxicity and can serve as templates in drug design.

DDQ as a versatile and easily recyclable oxidant: a systematic review.

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is the most widely used quinone with a high reduction potential, and it commonly mediates hydride transfer reactions and shows three accessible oxidation states: quinone (oxidized), semiquinone (one-electron-reduced), and hydroquinone (two-electron-reduced). DDQ has found broad utility as a stoichiometric oxidant in the functionalization of activated C-H bonds and the dehydrogenation of saturated C-C, C-O, and C-N bonds. The cost and toxicity of DDQ triggered recent efforts to develop methods that employ catalytic quantities of DDQ in combination with alternative stoichiometric oxidants. The aerobic catalytic approach was established for the selective oxidation of non-sterically hindered electron-rich benzyl methyl ethers and benzylic alcohols, and effectively extended to the oxidative deprotection of p-methoxybenzyl ethers to generate the alcohols in high selectivity. A combination of DDQ and protic acid is known to oxidize several aromatic donors to the corresponding cation radicals. The excited-state DDQ converts benzyls, heteroarenes, fluoroarenes, benzene, and olefins into their radical cation forms as well as chloride and other anions into their respective radicals. These reactive intermediates have been employed for the generation of C-C and C-X (N, O, or Cl) bonds in the synthesis of valuable natural products and organic compounds. To the best of our knowledge, however, there is still no review article exclusively describing the applications of DDQ in organic synthesis. Therefore, in the present review, we provide an overview of DDQ-induced organic transformations with their scope, limitations and the proposed reaction mechanisms.

Combating Essential Metal Toxicity: Key Information from Optical Spectroscopy.

Chelation therapy is one of the most effective and widely accepted methods of treatment to reduce metal toxicity caused by an excess amount of essential metals. Essential minerals play an important role in maintaining healthy human physiology. However, the presence of an excess amount of such essential metals can cause cell injury, which finally leads to severe life-threatening diseases. Chelating complexes can efficiently capture the targeted metal and can easily be excreted from the body. Commonly utilized metal chelators have major side effects including long-term damage to some organs, which has pointed out the need of less harmful biocompatible chelating agents. In this work, we have investigated the iron chelating property of curcumin through various spectroscopic tools by synthesizing and characterizing the iron-curcumin (Fe-Cur) complex. We have also investigated whether the synthesized materials are able to retain their antioxidant activity after the chelation of a substantial amount of metal ion. Our study unravels the improved antioxidant activity of the synthesized chelate complex. We further demonstrate that the proposed complex generates no significant reactive oxygen species (ROS) under dark conditions, which makes it a promising candidate for chelation therapy of iron toxicity. Femtosecond-resolved fluorescence studies further provide insight into the mechanism of activity of the new complex where electron transfer from ligand to metal has been observed prominently. Thus, the Fe-Cur complex has a potential to act as a dual activity medicine for excretion of toxic metal ions via chelation and as a therapeutic agent of oxidative stress caused by the metal ion as well.

Recent trends in smart and flexible three-dimensional cross-linked polymers: synthesis of chitosan-ZnO nanocomposite hydrogels for insulin drug delivery.

One set of major challenges and significant progress is attributed to the discovery of novel pharmaceuticals from the exoskeleton of marine crustacean wastes to minimize the environmental pollutants. In this strategy, high molecular weight chitosan was subsequently used in the synthesis of smart three-dimensional cross-linked network polymers. Super absorbent chitosan-ZnO nanocomposite hydrogels were synthesized via a terminated diisocyanate compound, a chitosan sample (NH2/NCO), and ZnO nanoparticles in different concentrations (1-7%). The discovered intelligent drugs were confirmed by spectral analyses such as FTIR, XRD, DLS, TGA and morphological analyses such as AFM, SEM, and TEM. The unique physical properties of chitosan-ZnO nanocomposite hydrogels towards environmental stimuli and the porosity of their structures have gained particular interest in fluorescence isothiocyanate-labeled insulin-loaded hydrogel nanocomposites for in vivo drug delivery into the rat nasal cavity. Confocal laser scanning microscopy (CLSM) was used to prove the absorption enhancement of fluorescein isothiocyanate (FITC)-labeled insulin-loaded hydrogels in the rat nasal cavity by this formulation. The formulation of hydrogels apparently decreased the blood glucose concentration (50-65% of initial blood glucose concentration) for at least 4-5.5 h after administration, and no apparent cytotoxicity was found after administration.

Allosteric Inhibitory Molecular Recognition of a Photochromic Dye by a Digestive Enzyme: Dihydroindolizine makes α-chymotrypsin Photo-responsive.

The structural-functional regulation of enzymes by the administration of an external stimulus such as light could create photo-switches that exhibit unique biotechnological applications. However, molecular recognition of small ligands is a central phenomenon involved in all biological processes. We demonstrate herein that the molecular recognition of a photochromic ligand, dihydroindolizine (DHI), by serine protease α-chymotrypsin (CHT) leads to the photo-control of enzymatic activity. We synthesized and optically characterized the photochromic DHI. Light-induced reversible pyrroline ring opening and a consequent thermal back reaction via 1,5-electrocyclization are responsible for the photochromic behavior. Furthermore, DHI inhibits the enzymatic activity of CHT in a photo-controlled manner. Simultaneous binding of the well-known inhibitors 4-nitrophenyl anthranilate (NPA) or proflavin (PF) in the presence of DHI displays spectral overlap between the emission of CHT-NPA or CHT-PF with the respective absorption of cis or trans DHI. The results suggest an opportunity to explore the binding site of DHI using Förster resonance energy transfer (FRET). Moreover, to more specifically evaluate the DHI binding interactions, we employed molecular docking calculations, which suggested binding near the hydrophobic site of Cys-1-Cys-122 residues. Variations in the electrostatic interactions of the two conformers of DHI adopt unfavorable conformations, leading to the allosteric inhibition of enzymatic activity.