Heterocyclic Phytochemicals as Anticancer Agents.

Cancer continues to be a major global health challenge, driving the need for the discovery of novel therapeutic agents. Among these, heterocyclic phytochemicals have gained significant attention for their potential as anticancer agents. This review offers a detailed analysis of various classes of heterocyclic compounds with proven anticancer properties, shedding light on their mechanisms of action. The study draws from a diverse array of natural product sources, detailing the chemical structures and bioactivities of these compounds. Key heterocyclic classes such as alkaloids, flavonoids, coumarins, and terpenoids are emphasized due to their potent anticancer effects. Heterocyclic phytochemicals exhibit diverse anticancer mechanisms, including the modulation of cellular pathways like apoptosis, angiogenesis, and cell cycle progression. The combination of heterocyclic phytochemicals with conventional cancer therapies has shown promising synergistic effects, enhanced treatment efficacy and reducing side effects. The review systematically evaluates both preclinical and clinical studies, revealing the efficacy, safety profiles, and pharmacokinetics of selected heterocyclic compounds. The promising outcomes highlighted in this review underscore the critical need for ongoing research to fully realize the therapeutic potential of heterocyclic phytochemicals in cancer treatment.

Study on the chemical components and anti-neuroinflammatory activity of the roots of Clausena excavate Burm. f.

The ethanol extract of the roots of Clausena excavata gave two previously undescribed coumarins, clauexcatin A (1) and clauexcatin B (2), as well as a pair of new isomers, trans/cis-clauexcatin C (3a, 3b), along with thirty known compounds. Among these, compound 33 was isolated from this genus for the first time. The structures of these compounds were elucidated based on their physicochemical properties and spectroscopic data. The anti-neuroinflammatory activities were assessed using LPS-activated BV-2 microglial cells. Compounds 6, 8, 17, 24, 29, and 30 exhibited significant inhibition of nitric oxide release in a dose-dependent manner, with their inhibitory effects being 1.2 to 10.9 times greater than that of the positive control (minocycline).

A comprehensive review on the potential of coumarin and related derivatives as multi-target therapeutic agents in the management of gynecological cancers.

Current treatments for gynecological cancers include surgery, radiotherapy, and chemotherapy. However, these treatments often have significant side effects. Phytochemicals, natural compounds derived from plants, offer promising anticancer properties. Coumarins, a class of benzopyrone compounds found in various plants like tonka beans, exhibit notable antitumor effects. These compounds induce cell apoptosis, target PI3K/Akt/mTOR signaling pathways, inhibit carbonic anhydrase, and disrupt microtubules. Additionally, they inhibit tumor multidrug resistance and angiogenesis and regulate reactive oxygen species. Specific coumarin derivatives, such as auraptene, praeruptorin, osthole, and scopoletin, show anti-invasive, anti-migratory, and antiproliferative activities by arresting the cell cycle and inducing apoptosis. They also inhibit metalloproteinases-2 and -9, reducing tumor cell migration, invasion, and metastasis. These compounds can sensitize tumor cells to radiotherapy and chemotherapy. Synthetic coumarin derivatives also demonstrate potent antitumor and anticancer activities with minimal side effects. Given their diverse mechanisms of action and minimal side effects, coumarin-class phytochemicals hold significant potential as therapeutic agents in gynecological cancers, potentially improving treatment outcomes and reducing side effects. This review will aid in the synthesis and development of novel coumarin-based drugs for these cancers.

Three new coumarins from Notopterygium incisum with potential anti-inflammatory activity.

Three previously undescribed coumarins (1-3) were obtained from the roots of Notopterygium incisum. Their chemical structures were elucidated using a variety of spectroscopic techniques and chemical calculations. The inhibitory effects of these new compounds on NO production and pro-inflammatory factors (IL-1ß, IL-6, and TNF-α) in LPS-stimulated RAW 264.7 cells were investigated. Further studies revealed that compound 1 suppressed the expression of COX-2 and iNOS while also reduced ROS accumulation. Western blot analysis demonstrated that compound 1 could inhibit the PI3K/AKT pathway by decreasing the levels of p-PI3K and p-AKT. Collectively, these findings suggest that compounds 1-3 exhibit promising anti-inflammatory properties.

Establishing a coumarin production platform by protein and metabolic engineering.

Coumarins are a vast family of natural products with diverse biological activities. Cinnamyl-CoA ortho-hydroxylases (CCHs) catalyze the gateway and rate-limiting step in coumarin biosynthesis. However, engineering CCHs is challenging due to the large size of the substrates and the vague structure-activity relationship. Herein, directed evolution and structure-guided engineering were performed to engineer a CCH (AtF6'H from Arabidopsis thaliana) using a fluorescence-based screening method, yielding the transplantable surface mutations and the substrate-specific pocket mutations with improved activity. Structural analysis and molecular dynamics simulations elucidated the conformational changes that led to increased catalytic efficiency. Applying appropriate variants with the optimized upstream biosynthetic pathways improved the titers of three simple coumarins by 5 to 22-fold. Further introducing glycosylation modules resulted in the production of four coumarin glucosides, among which the titer of aesculin was increased by 15.7-fold and reached 3 g/L in scale-up fermentation. This work unleashed the potential of CCHs and established an Escherichia coli platform for coumarins production.

A Step Towards Optimization of Amide-Linked Coumarin Pharmacophore: As an Anti-HIV Agent.

The aim of the present investigation is to identify effective anti-HIV drugs through the in-silico virtual screening of the coumarin pharmacophore with or without substituents. Virtual screening started with target identification through computation docking and interactions, binding affinity through molecular dynamics, and the ADMET profile through the use of various enzymes. The target study suggests that the target is involved in various stages of HIV replication and in determining the ways in which non-nucleoside reverse transcriptase inhibitors (RTIs) influence it. The interaction pattern and simulation study conclude the specific affinity of coumarin pharmacophore to the HIV's reverse transcriptase enzyme, especially 3HVT. Moreover, the amide linkage worked as a synergistic bridge to provide more interaction to the pharmacophore. The initial results led to the determination of 83 virtual amide-like molecules, which were screened through docking and MD studies (100 ns) on the best-suited enzyme HIV's reverse transcriptase enzyme, such as PDB ID "3HVT". The virtual screening study revealed the high affinity of compounds 7d and 7e with the lowest IC50 values of 0.729 and 0.658 µM; moreover, their metabolism pattern study, toxicity, and QED values in a range of 0.31-0.40 support a good drug candidate. The two compounds were also synthesized and characterized for future in vitro and in vivo studies. The in silico-based descriptor of compounds 7d and 7e indicates the potential future and provides the best two molecules and their synthetic route for the development of a more effective drug to combat HIV/AIDS epidemics.

Non-sulfonamide bacterial CA inhibitors.

Non-sulfonamide chemical moieties able to inhibit the bacterial (b) expressed Carbonic Anhydrases (CAs; EC 4.2.1.1) constitute an important alternative to the prototypic modulators discussed in Chapter 6, as give access to large and variegate chemical classes, also of the natural origin. This contribution reports the main classes of compounds profiled in vitro on the bCAs and thus may be worth developing for the validation process of this class of enzymes.

A Ligand-Free Approach towards Coumarin Analogs via Natural Deep Eutectic Solvent-Mediated Suzuki-Miyaura Coupling.

A ligand-free approach for the Suzuki-Miyaura cross coupling reaction using Natural Deep Eutectic Solvents (NaDES) towards coumarin analogs is described. A model reaction between the synthetically prepared 3-(4-acetyloxy-phenyl)-6-bromo-4-methyl-coumarin (3b) and phenylboronic acid was performed in five different NaDES as well as in pure glycerol, using two inorganic bases and palladium catalysts. The reaction proceeded smoothly in Choline Chloride/Glycerol (ChCl/Gly) and Betaine/Glycerol (Bet/Gly) NaDES at 90 °C in 24 h, affording the desired product in high yields up to 95%. The combination of K2CO3, Pd(OAc)2 and ChCl/Gly NaDES provided optimum yields and high purity of the desired compounds, while the solvent was successfully recycled and reused up to two times. The developed methodology is applicable to boronic acids bearing various substituents. The formation of palladium nanoparticles in the reaction mixture was observed, and the size of the nanoparticles was associated with the reaction yield. In addition, in all the glycerol-based NaDES, an effective removal of the acetyl group of the acetyloxy-coumarin analogs was observed; thus, it is noteworthy that the Suzuki-Miyaura coupling and the deacetylation reaction were achieved in one pot. The ten novel coumarin derivatives synthesized were structurally characterized using 1D and 2D NMR spectroscopy and were tested for their cytotoxicity against the A431 squamous cancer cell line, presenting significant activity.

Discovery of Coumarins from Zanthoxylum dimorphophyllum var. spinifoliumas and Their Potential against Rheumatoid Arthritis.

In the present study, a series of coumarins, including eight undescribed bis-isoprenylated ones Spinifoliumin A-H, were isolated and identified from the aerial parts of Zanthoxylum dimorphophyllum var. spinifolium (ZDS), a plant revered in traditional Chinese medicine, particularly for treating rheumatoid arthritis (RA). The structures of the compounds were elucidated using 1D and 2D NMR spectroscopy, complemented by ECD, [Rh2(OCOCF3)4]-induced ECD, Mo2(OAc)4 induced ECD, IR, and HR-ESI-MS mass spectrometry. A network pharmacology approach allowed for predicting their anti-RA mechanisms and identifying the MAPK and PI3K-Akt signaling pathways, with EGFR as a critical gene target. A CCK-8 method was used to evaluate the inhibition activities on HFLS-RA cells of these compounds. The results demonstrated that Spinifoliumin A, B, and D-H are effective at preventing the abnormal proliferation of LPS-induced HFLS-RA cells. The results showed that compounds Spinifoliumin A, D, and G can significantly suppress the levels of IL-1ß, IL-6, and TNF-α. Moreover, molecular docking methods were utilized to confirm the high affinity between Spinifoliumin A, D, and G and EGFR, SRC, and JUN, which were consistent with the results of network pharmacology. This study provides basic scientific evidence to support ZDS's traditional use and potential clinical application.

Coumarins with Different Substituents from Leonurus japonicus Have Opposite Effects on Uterine Smooth Muscle.

Leonurus japonicus Houtt is an exceptional medicinal herb used to treat obstetrical and gynecological diseases in traditional Chinese medicine, and it has significant effects on the treatment of dysmenorrhea and postpartum hemorrhage. This study investigated the effects of coumarins with diverse substituent groups from L. japonicus on isolated uterine smooth muscle and the preliminary mechanism of the most effective compound. Eight coumarins isolated from L. japonicus were assessed for their effects on the isolated uterine smooth muscle of nonpregnant rats in vitro. Coumarins 1 and 2 significantly promoted the contraction of rat uterine smooth muscle strips, whereas coumarins 3-5 showed remarkable relaxing effects against oxytocin (OT)-induced rat uterine smooth muscle contraction. Further mechanism investigations revealed that bergapten (coumarin 1) significantly increased the level of Ca2+ in uterine tissues by promoting extracellular Ca2+ influx and intracellular Ca2+ release, which were related to the activation of L-type Ca2+ channels and α-receptors. By contrast, osthole (coumarin 5), an α receptor antagonist, inhibited OT-induced uterine smooth muscle contraction by decreasing the level of Ca2+ in uterine tissues via inhibition of extracellular Ca2+ influx and intracellular Ca2+ release. This study demonstrates that the coumarins from L. japonicus are effective substances for regulating uterine smooth muscle contraction, but different coumarins with diverse substituent groups have different, even opposite effects. It can be inferred that coumarins are closely related to the efficacy of L. japonicus in the treatment of dysmenorrhea and postpartum hemorrhage.

Coumarins as versatile therapeutic phytomolecules: A systematic review.

BACKGROUND: Coumarins, abundantly distributed in a plethora of biologically active compounds, serve as a fundamental motif in numerous natural products, drugs, and therapeutic leads. Despite their small size, they exhibit a diverse range of biological activities, intriguing researchers with their immense pharmacological potential. PURPOSE: This study consolidates the evidence regarding the essential role of coumarins in modern drug discovery, exploring their broad-spectrum pharmaceutical effects, structural versatility, and mechanisms of action across various domains. METHODS: For literature search, we utilized PubMed, Google scholar, and SciFinder databases. Keyword and keyword combinations such as "coumarins", "natural coumarins", "specific natural coumarins for particular diseases", and "therapeutic effects" were employed to retrieve relevant studies. The search encompassed articles published between 2005 and 2023. Selection criteria included studies reporting on the pharmacological activities of natural coumarins against various diseases. RESULTS: The results highlight the therapeutic potential of natural coumarins against various diseases, demonstrating anti-cancer, anti-oxidant, and anti-inflammatory activities. They also act as monoamine oxidase inhibitors and phosphodiesterase inhibitors, and as anti-thrombotic, anti-diabetic, and hepatoprotective agents. They also show efficacy against diabetic nephropathy, neurodegenerative diseases, microbial infections and many other diseases. CONCLUSION: This review underscores the significant role of natural coumarins in medicinal chemistry and drug discovery. Their diverse biological activities and structural versatility make them promising therapeutic agents. This study serves as a catalyst for further research in the field, aiming to address emerging challenges and opportunities in drug development.

An Overview on the Synthesis of Lamellarins and Related Compounds with Biological Interest.

Lamellarins are natural products with a [3,4]-fused pyrrolocoumarin skeleton possessing interesting biological properties. More than 70 members have been isolated from diverse marine organisms, such as sponges, ascidians, mollusks, and tunicates. There is a continuous interest in the synthesis of these compounds. In this review, the synthetic strategies for the synthesis of the title compounds are presented along with their biological properties. Three routes are followed for the synthesis of lamellarins. Initially, pyrrole derivatives are the starting or intermediate compounds, and then they are fused to isoquinoline or a coumarin moiety. Second, isoquinoline is the starting compound fused to an indole moiety. In the last route, coumarins are the starting compounds, which are fused to a pyrrole moiety and an isoquinoline scaffold. The synthesis of isolamellarins, azacoumestans, isoazacoumestans, and analogues is also described. The above synthesis is achieved via metal-catalyzed cross-coupling, [3 + 2] cycloaddition, substitution, and lactonization reactions. The title compounds exhibit cytotoxic, multidrug resistance (MDR), topoisomerase I-targeted antitumor, anti-HIV, antiproliferative, anti-neurodegenerative disease, and anti-inflammatory activities.

Novel 3-substituted coumarins inspire a custom pharmacology prediction pipeline: an anticancer discovery adventure.

Aim: This research aims to expand the established pharmacological space of tumor-associated carbonic anhydrases (TACAs) by exploring the synthetically accessible chemical space of 3-substituted coumarins, with the help of in silico pharmacology prediction.Materials & methods: 52 novel 3-substituted coumarins were sketched, prioritizing synthetic feasibility. Their pharmacological potentials were estimated using a custom machine-learning approach. 17 compounds were predicted as cytotoxic against HeLa cells by interfering with TACAs. Those compounds were synthesized and biologically tested against HeLa cells. The three most potent compounds were assayed against multiple carbonic anhydrases, and their enzyme binding mechanism(s) were studied using molecular docking.Results: Experimental results exhibited pronounced consensus with in silico pharmacology predictions.Conclusion: Novel 3-substituted coumarins are herein dispatched to the cancer therapeutics space.

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Immunomodulatory and antioxidant effect of liposomal auraptene against cyclophosphamide-induced immunosuppression in BALB/c mice.

INTRODUCTION: Cyclophosphamide (CP), which is a commonly used chemotherapy drug, can lead to a range of side effects such as immunosuppression, bone marrow suppression, leukopenia, and oxidative stress. This study aims to explore the effects of Auraptene (AUR), which has immunomodulatory and antioxidant properties, on immune function in mice that are experiencing suppression induced by CP. MATERIALS AND METHODS: The experiment involved 60 male BALB/c mice that underwent a 10-day treatment. On days 1, 3, and 9, CP was given at 80 mg/kg IP doses to induce immunosuppression. The mice were divided into five groups: Control group, CP group, CP + liposomal AUR 0.2 mg/kg (AUR 0.2), CP + liposomal AUR 0.25 mg/kg (AUR 0.25), and liposomal vehicle group. Various parameters were measured, including mouse weight, immune organ weight index (spleen and thymus), spleen and thymus histopathology, levels of inflammatory cytokines (IL2, IL10, IL4, IFN-γ), TH1/TH2 balance ratio, IgG and IgM immunoglobulin levels, white blood cell count, platelets, neutrophils, lymphocytes, and oxidative activity measured by MDA, SOD, and Total Antioxidant. RESULTS: In the group treated with CP, the mice showed a significant decrease in weight compared to the control group. In contrast, the group treated with AUR maintained their weight and did not show a significant difference from the control group. AUR 0.25 reduced the damage to the spleen and thymus caused by CP. Additionally, AUR 0.25 demonstrated a significant decrease in IL4 and IL10 levels compared to the CP group (p = 0.04), approaching the levels of the control group. Furthermore, IL2 and IFN-γ levels in the AUR 0.25 group significantly increased (p = 0.04) compared to the CP group, reaching levels similar to the control group. AUR also increased serum IgM and IgG levels two to three times compared to the CP group, approaching the levels of the control group. MDA levels in the AUR 0.25 group decreased to normal and control levels. AUR 0.25 also showed increased SOD and Total Antioxidant levels. Additionally, white blood cells, platelets, neutrophils, and lymphocytes in the AUR group significantly increased compared to the CP group, reaching normal levels similar to the control group. The TH1/TH2 ratio in the AUR group exhibited a significant increase of two and a half times (p = 0.002) compared to the CP group. CONCLUSION: These results show that AUR protects against the side effects of CP by increasing the function of the humoral and cellular immune system through the balance of TH1/TH2 and increasing the level of immunoglobulins, as well as increasing the antioxidant activity and the protective role of cytotoxicity.

New Insights Concerning Phytophotodermatitis Induced by Phototoxic Plants.

The present review explores the underlying mechanisms of phytophotodermatitis, a non-immunologic skin reaction triggered by certain plants followed by exposure to ultraviolet radiation emitted by sunlight. Recent research has advanced our understanding of the pathophysiology of phytophotodermatitis, highlighting the interaction between plant-derived photosensitizing compounds (e.g., furanocoumarins and psoralens) and ultraviolet light leading to skin damage (e.g., erythema, fluid blisters, edema, and hyperpigmentation), identifying these compounds as key contributors to the phototoxic reactions causing phytophotodermatitis. Progress in understanding the molecular pathways involved in the skin's response to these compounds has opened avenues for identifying potential therapeutic targets suitable for the management and prevention of this condition. The review emphasizes the importance of identifying the most common phototoxic plant families (e.g., Apiaceae, Rutaceae, and Moraceae) and plant species (e.g., Heracleum mantegazzianum, Ruta graveolens, Ficus carica, and Pastinaca sativa), as well as the specific phytochemical compounds responsible for inducing phytophototoxicity (e.g., limes containing furocoumarin have been linked to lime-induced photodermatitis), underscoring the significance of recognizing the dangerous plant sources. Moreover, the most used approaches and tests for accurate diagnosis such as patch testing, Wood's lamp examination, or skin biopsy are presented. Additionally, preventive measures such as adequate clothing (e.g., long-sleeved garments and gloves) and treatment strategies based on the current knowledge of phytophotodermatitis including topical and systemic therapies are discussed. Overall, the review consolidates recent findings in the field, covering a diverse array of phototoxic compounds in plants, the mechanisms by which they trigger skin reactions, and the implications for clinical management. By synthesizing these insights, we provide a comprehensive understanding of phytophotodermatitis, providing valuable information for both healthcare professionals and researchers working to address this condition.

Mitigating the resistance of MCF-7 cancer cells to Doxorubicin under hypoxic conditions with novel coumarin based carbonic anhydrase IX and XII inhibitors.

In the present study, the design and synthesis of novel coumarin derivatives 8a-h, 11a-d and 16a-c as potential selective inhibitors for the tumor associated human carbonic anhydrase isoforms (hCA IX and XII) was reported. All the newly synthesized derivatives showed potent to mild activity against the targeted CA IX (KI = 0.08-9.57 µM), with selectivity indices over CA I (SI = 2.0-21.9) and over CA II (SI = 1.1-15.7). They showed similar activities against CA XII (KI = 0.06-9.48 µM) with selectivity indices over CA I (SI = 1.4-21.2) and CA II (SI = 0.9-15.5). Compound 16b featuring sulfonamide function possessed promising inhibitory activities against the targeted isoforms CA IX and XII with KI values of 0.08 and 0.06 µM, respectively. Interestingly, it was found that using compound 16b at a nontoxic concentration as an adjuvant with Doxorubicin against MCF-7 cells enhanced the cytotoxicity under hypoxia by almost 3.5 folds; IC50 decreased from 25.74 to 7.43 µM. Therefore, compound 16b restored the cytotoxicity of Doxorubicin against MCF-7 cells under hypoxia, almost as normoxia. Furthermore, flow cytometry analysis of a combination treatment of compound 16b and Doxorubicin to the MCF7 cell line revealed an increase in cell cycle arrest at the G2/M phase and a more efficient apoptotic effect than Doxorubicin alone. Furthermore, compound 16b showed no cytotoxicity against normal breast MCF-10A cell line (IC50 = 296.25 µM).

Genes to specialized metabolites: accumulation of scopoletin, umbelliferone and their glycosides in natural populations of Arabidopsis thaliana.

BACKGROUND: Scopoletin and umbelliferone belong to coumarins, which are plant specialized metabolites with potent and wide biological activities, the accumulation of which is induced by various environmental stresses. Coumarins have been detected in various plant species, including medicinal plants and the model organism Arabidopsis thaliana. In recent years, key role of coumarins in maintaining iron (Fe) homeostasis in plants has been demonstrated, as well as their significant impact on the rhizosphere microbiome through exudates secreted into the soil environment. Several mechanisms underlying these processes require clarification. Previously, we demonstrated that Arabidopsis is an excellent model for studying genetic variation and molecular basis of coumarin accumulation in plants. RESULTS: Here, through targeted metabolic profiling and gene expression analysis, the gene-metabolite network of scopoletin and umbelliferone accumulation was examined in more detail in selected Arabidopsis accessions (Col-0, Est-1, Tsu-1) undergoing different culture conditions and characterized by variation in coumarin content. The highest accumulation of coumarins was detected in roots grown in vitro liquid culture. The expression of 10 phenylpropanoid genes (4CL1, 4CL2, 4CL3, CCoAOMT1, C3'H, HCT, F6'H1, F6'H2,CCR1 and CCR2) was assessed by qPCR in three genetic backgrounds, cultured in vitro and in soil, and in two types of tissues (leaves and roots). We not only detected the expected variability in gene expression and coumarin accumulation among Arabidopsis accessions, but also found interesting polymorphisms in the coding sequences of the selected genes through in silico analysis and resequencing. CONCLUSIONS: To the best of our knowledge, this is the first study comparing accumulation of simple coumarins and expression of phenylpropanoid-related genes in Arabidopsis accessions grown in soil and in liquid cultures. The large variations we detected in the content of coumarins and gene expression are genetically determined, but also tissue and culture dependent. It is particularly important considering that growing plants in liquid media is a widely used technology that provides a large amount of root tissue suitable for metabolomics. Research on differential accumulation of coumarins and related gene expression will be useful in future studies aimed at better understanding the physiological role of coumarins in roots and the surrounding environments.

A review of the ethnomedicinal, phytochemical, and pharmacological properties of the Ferulago genus based on Structure-Activity Relationship (SAR) of coumarins.

BACKGROUND: The Ferluago W.D.J. Koch genus includes 48 accepted perennial herbs that are distributed in the Mediterranean region, Southeast Europe, Central and Middle East of Asia. These plants are widely used in folk and conventional medicine due to their biological benefits such as anti-microbial, anti-inflammatory, anti-cancer, and immunomodulatory properties. Conducting a comprehensive review based on the structure activity relationships (SARs) of the coumarins, which has not been previously documented, can lead to a better insight into the genus Ferulago and its beneficial therapeutic activities. METHODS: This review covers literature from 1969 to 2023, were collected from various scientific electronic databases to review phytochemical, pharmacological, and ethnopharmacological data of Ferulago species, as well as latest information on the SAR of reported coumarins from this genus. RESULTS: Phytochemical studies showed that the biological actions of this genus are mediated by the reported specialized metabolites, such as coumarins and flavonoids. Simple coumarins, prenylated coumarins, furanocoumarins, and pyranocoumarins are the largest subclasses of coumarins found in diverse Ferulago species, which have discussed the biological effects of them with a focus on the Structure-Activity Relationship (SAR). For example, prenylated coumarins have shown potential leishmanicidal and anti-neuropsychiatric effects when substituted with a prenyl group at the 7-hydroxy, as well as the C6 and C8 positions in their scaffold. Similarly, furanocoumarins exhibit varied biological activities such as anti-inflammatory, anti-proliferative, and anti-convulsant effects. Modifying substitutions at the C5 and C6 positions in furanocoumarins can enhance these activities. CONCLUSION: This study conducted a comprehensive review of all available information on the phytochemical and pharmacological characteristics of Ferulago species. Given the high occurrence of coumarins in this genus, which exhibit potential anti-Alzheimer and anti-microbial properties, it presents promising new therapeutic avenues for addressing these common issues. Further investigation is needed to understand the molecular-level mechanisms of action and to explore their clinical applications.

Design, Synthesis, and Photophysical Characterization of Biocompatible Thermally Activated Delayed Fluorescent Carbazole-Coumarins for Sensing Applications.

A series of fluorescent carbazole-coumarins exhibiting good photoluminescence quantum yields and thermally activated delayed fluorescence (TADF) properties have been designed and synthetized using computer-aided density functional theory calculations. The TADF characteristics of the carbazole-coumarins were systematically explored both in solution and in the solid state, utilizing poly(methyl methacrylate) (PMMA) as a matrix. The study revealed that the introduction of carbazole units onto the coumarin benzene ring led to compounds with thermally induced reverse intersystem crossing and delayed fluorescence. The study further demonstrated the potential utility of these compounds in practical applications by incorporating them into a Cmr-PMMA-based sensor for molecular oxygen detection. The resulting sensor exhibited promising performance, highlighting the adaptability and efficacy of the synthesized TADF-carbazole-coumarin compounds for reversible molecular oxygen sensing.

Tweezer Dyads for H-Bond Assisted Cooperativity in Tandem Uncaging Systems.

"Tandem" uncaging systems, in which a photolabile protecting group (PPG) is sensitized by an energy-harvesting antenna, may increase the photosensitivity of PPGs by several orders of magnitude for two-photon (2P) photorelease. Yet, they remain poorly accessible because of arduous multi-step synthesis. In this work, we design efficient tandem uncaging systems by (i) using a convenient assembly of the building blocks relying on click chemistry, (ii) introducing H-bonding induced proximity thus facilitating (iii) photoinduced electron transfer (PeT) as a cooperative mechanism. A strong two-photon absorber electron-donating quadrupolar antenna and various electron-accepting PPGs (mDEAC, MNI or MDNI) were clicked stepwise onto a "tweezer-shaped" pyrido-2,6-dicarboxylate platform whose H-bonding and π-stacking abilities were exploited to keep the antenna and the PPGs in close proximity. The different electron-accepting ability of the PPGs led to dyads with wildly different behaviors. Whilst the MDNI and MNI dyads showed poor dark stability or no photo-uncaging ability due to their too high electron-accepting character, the mDEAC dyad benefited from optimum redox potentials to promote PeT and slow down charge recombination, resulting in enhanced uncaging quantum yield (Φu=0.38) compared to mDEAC (Φu=0.014). This unique combination resulted in large 2P photo-sensitivity in the near-infrared window (240 GM at 710 nm).