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The hetero-Diels-Alder (HDA) reaction between the ambident heterodiene 3-methylene-2,4-chromandione (MCDO) and non-symmetric methyl vinyl ether (MVE) is investigated using the molecular electron density theory (MEDT) at the B3LYP/6-311G(d,p) computational level. The aim of this study is to gain insight into its molecular mechanism and to elucidate the factors that control the selectivity found experimentally. DFT-based reactivity indices reveal that MCDO exhibits strong electrophilic characteristics, while MVE displays a strong nucleophilic character. Meanwhile, the Parr function explains the ortho regioselectivity of this HDA reaction. The highly polar nature of this HDA reaction, supported by the high global electron density transfer (GEDT) taking place at the transition state structures (TSs), accounts for the very low activation energy associated with the most favorable TS-4on . The ambident nature of MCDO allows for the formation of two constitutional isomeric cycloadducts. In the case of MVE, pseudocyclic selectivity is attained using a thermodynamic control. This polar HDA reaction displays an endo stereoselectivity and a complete ortho regioselectivity. A comparative relative interacting atomic energy (RIAE) analysis of the two diastereomeric structures TS-4on and TS-6on indicates a high degree of likeness, which explains the low pseudocyclic selectivity under kinetic control.

The bushy plant Withania frutescens (L.) Pauquy is well distributed in the West-Mediterranean area, notably in the south of Spain, Algeria and Morocco where is it is used traditionally for the treatment of various human diseases, including diabetes. Unlike the two major species W. somnifera and W. coagulans extensively studied, the genomically close species W. frutescens has been much less investigated. Nevertheless, this shrub species displays a comparable phytochemical profile and marked antioxidant and anti-inflammatory properties, at the origin of reported pharmacological effects and its traditional uses. Here we have analyzed the diversity of biological effects reported with leaves and root extracts of W. frutescens. Hydroalcoholic extracts prepared from the aerial parts of the plant have revealed antihyperglycemic and cell-protective activities along with antimicrobial and anticorrosive effects. The extracts contained diverse polyphenolic compounds and a few alkaloids (calystegines) but most of the observed effects have been attributed to the presence of withanolides which are modified C28 ergostane-type steroids. Our analysis focused in part on specific withanolides found in W. frutescens, in particular an unusual 3-O-sulfated withanolide considered as a potential pro-drug of the major active compound withaferin A (WA) and a lead compound for the development of a potential drug candidate. The mechanism of action of this sulfated WA analogue is discussed. Altogether, our unprecedented extensive analysis of W. frutescens highlighted the pharmacological potential of this atypical medicinal plant. By analogy with the major cultivated Withania species, the market potential of little-known plant is underlined., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Inhibitors of monoamine oxidases (MAOs) are of interest for the treatment of neurodegenerative disorders and other human pathologies. In this frame, the present work describes different synthetic strategies to obtain MAO inhibitors via the coupling of the aminocoumarin core with arylsulfonyl chlorides followed by copper azide-alkyne cycloaddition, leading to coumarin-sulfonamide-nitroindazolyl-triazole hybrids. The nitration position on the coumarin moiety was confirmed through nuclear magnetic resonance spectroscopy and molecular electron density theory in order to elucidate the molecular mechanism and selectivity of the electrophilic aromatic substitution reaction. The coumarin derivatives were evaluated for their inhibitory potency against monoamine oxidases and cholinesterases. Molecular docking calculations provided a rational binding mode of the best compounds in the series with MAO A and B. The work identified hybrids 14a - c as novel MAO inhibitors, with a selective action against isoform B, of potential interest to combat neurological diseases.

Introduction: Cubeb, Piper cubeba L., has been used for centuries in traditional medicine and culinary practices, with a wide range of biological and pharmacological activities., Objective: Herein, we determined the phytochemical profile, mineral, fatty acids, and amino acid contents of P. cubeba berries and assessed the dermacosmeceutical properties of their water extract and essential oil (EO). These included assessing their antioxidant and antibacterial activities as well as their in vitro inhibitory activities against tyrosinase and elastase enzymes. In addition, molecular docking and molecular dynamics studies were performed on the major identified compounds of the EO., Results and Discussion: A total of forty-three compounds belonging to organic acids, phenolic acids and flavonoids were found in the water extract, while 36 volatile compounds were identified in the EO with Z-isoeugenol, dihydroeugenol, β-pinene, E-caryophyllene, and 1,8-cineole as major constituents. The berries were found to be rich in sodium and iron, have moderate zinc content along with low contents of total nitrogen, phosphorus, and potassium. Amino acid analysis revealed a considerable concentration of isoleucine and phenylalanine, whereas 11,14,17-eicosatrienoic acid and linoleic acid were identified as the major fatty acids. In the DPPH and FRAP assays, the water extract elicited considerable antioxidant activity compared to the reference compounds. Enzyme inhibitory assays revealed that the EO had a potential to inhibit tyrosinase and elastase enzymes with IC 50 values of 340.56 and 86.04 μg/mL, respectively. The water extract and EO completely inhibited the bacterial growth at MIC of 50 mg/mL and 20%, respectively. At sub-MIC concentrations, the extract and the EO substantially reduced the biofilm formation by up to 26.63 and 77.77%, respectively, as well as the swimming and swarming motilities in a dose-dependent manner. Molecular docking and molecular dynamics showed that the five main components of P. cubeba EO could be the major contributors to the elastase and tyrosinase inhibitory effect., Conclusion: This study emphasizes the promising potential of P. cubeba as a valuable source of natural compounds that can be utilized for the development of innovative pharmaceuticals, dietary supplements, and dermacosmeceutical agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Drissi, Mahdi, Ortaakarsu, Abdelfattah, Bakrim, Khatib, Mahmoud, Bouissane and Sobeh.)

Ephedra species are among the most popular herbs used in traditional medicine for a long time. The ancient Chinese medical book "Treatise on Febrile Diseases" refers to the classic traditional Chinese medicine prescription Ge Gen decoction, which consists of seven herbs, including an Ephedra species. Ephedra species are utilized all over the world to treat symptoms of the common cold and coughs, and to combat major human diseases, such as asthma, cancers, diabetes, cardiovascular and digestive disorders, and microbial infections. This study aimed at identifying specific Ephedra species used traditionally in Morocco for therapeutic purposes. The plant parts, their preparation process, and the treated pathologies were identified and analyzed. The results revealed five ethnobotanically important species of Ephedra: Ephedra alata Decne, Ephedra altissima Desf., Ephedra distachya L., Ephedra fragilis Desf., and Ephedra nebrodensis Tineo. These species are used traditionally in Morocco for treating people with diabetes, cancer, rheumatism, cold and asthma, hypertension, influenza virus infection, and respiratory ailments. In addition, they are occasionally used as calefacient agents, to regulate weight, or for capillary care. Few studies have underlined the antibacterial and antioxidant activities of some of these Moroccan Ephedra species, but little information is available regarding the natural products at the origin of the bioactivities. Further phytochemical investigations and clinical data are encouraged to better support the use of these plants., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Essential oils are of great interest due to their potent pharmaceutical and biological activities. In this study, essential oils extracted from Origanum compactum and Thymus zygis originating from the Middle Atlas of Morocco were investigated. Their chemical compositions were analyzed using gas chromatography and mass spectrometry, while the assessment of the trapping power of the radical (DPPH: 1,1-diphenyl-2-picrylhydrazyl) and the reducing antioxidant potential of ferric ions (FRAP: Ferric Reducing Antioxidant Power) were performed in order to evaluate the antioxidant activity. Their antibacterial potency was tested against six bacterial strains through the disk diffusion method. The chromatography analyses of the extracted essential oils highlighted the presence of two main components, namely carvacrol at 75.70% in O. compactum and thymol at 40.67% in T. zygis . The antioxidant activity tests showed that both essential oils demonstrated a significant antioxidant activity comparable to the positive control (e.g., ascorbic acid). The antibacterial activity results showed a strong antimicrobial effect for both essential oils, compared to synthetic antibiotics. This study affirms the presence of bioactive components with interesting antioxidant and antibacterial activities in the essential oils extracted from Origanum compactum and Thymus zygis , which could find several applications in the food and pharmaceutical industries through the substitution of synthetic antioxidants and antibiotics.

Type 2 diabetes mellitus (T2DM) is a metabolic syndrome known to contribute to impaired wound healing. This condition can be further worsened by excessive melanin production, elastin degradation, and chronic infections at the wound site, potentially leading to melasma and diabetic dermopathy. The purpose of this study was to investigate the phytochemical profile and inhibitory effects of Tetraclinis articulata essential oil (TAEO) on target enzymes involved in diabetes pathogenesis and chronic wound remodeling, namely α -amylase, α -glucosidase, tyrosinase, and elastase, as well as its in vitro antibacterial activity. Gas chromatography and mass spectrometry (GC-MS) analysis of TAEO led to the identification of 46 volatile compounds, representing 96.61 % of TAEO. The major metabolites were bornyl acetate (29.48 %), α -pinene (8.96 %), germacrene D (7.70 %), and d-limonene (5.90 %). TAEO exhibited limited scavenging activity against DPPH free radicals, whereas the FRAP and ABTS assays indicated a relatively higher antioxidant activity. Remarkably, TAEO disclosed a promising in vitro antidiabetic activity against α -glucosidase with an IC 50 value of 178 ± 1.6 μg/mL, which is comparable to the standard inhibitor acarbose (IC 50  = 143 ± 1.1 μg/mL). In silico , molecular docking analysis against α -glucosidase identified 15 compounds that interacted with the enzyme's active site, whereas skin permeability and sensitization assessments indicated that 26 out of the 44 identified volatile compounds were predicted to be free from any skin sensitivity risk. On the other hand, moderate inhibitory activity was recorded against α -amylase, tyrosinase, and elastase. Notably, TAEO at 5 % significantly suppressed biofilm formation by P. aeruginosa, S. aureus , and E. faecalis , common skin pathogens associated with wound infections, and reduced their swarming motility. Our findings suggest that TAEO may hold the potential as a natural remedy for type 2 diabetes and its associated co-morbidities, especially chronic wounds., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

New leukotriene B4 (LTB4) antagonists have been synthesized that can be considered as potential anti-inflammatory drugs. Structures containing the dioxygenated nucleus of 1,4-benzodioxine constitute a potential group of leukotriene B4 (LTB4) antagonists. The objective of this study was to access efficient and selective LTB4 antagonists as a way to elucidate the role of LTB4 in inflammatory processes and therefore allow the development of new types of structures based on 1,4-benzodioxine. Forty-one new 1,4-benzodioxine molecules substituted at different positions of the heterocyclic nucleus were synthesized to determine the minimum structural requirements by studying structure-activity relationships. Eighteen of them were tested in vitro and in vivo for their anti-inflammatory activity related to the antagonist character of LTB4. Pharmacological tests have shown satisfactory in vitro activity for compounds 24b, 24c and 24e with IC50's of 288, 439, 477 nM respectively. The results of the in vivo tests, carried out with the compound that presented greater activity in the in vitro tests 24b, have shown significant anti-inflammatory properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

In Morocco, many applications in ethnomedicine on Ajuga iva (L.) have been recognized as able to treat various pathologies such as diabetes, stress, and microbial infections. The objective of this work is to carry out phytochemical, biological, and pharmacological investigations on the extracts of Ajuga iva leaves in order to confirm its therapeutic effects. The phytochemical screening carried out on the different extracts of Ajuga iva showed its richness in primary (lipids and proteins) and secondary metabolites (flavonoids, tannins, reducing compounds, oses, and holoside. The best contents of polyphenols, flavonoids, and tannins evaluated by spectrophotometric methods were found in the hydroethanolic extract (69.850 ± 2.783 mg EAG/g DE, 17.127 ± 0.474 mg EQ/g DE, 5.566 ± 0.000 mg EQC/g DE), respectively. Analysis of the chemical composition of the aqueous extract by LC/UV/MS revealed 32 polyphenolic compounds including ferulic acid (19.06%), quercetin (10.19%), coumaric acid (9.63%), and apigenin-7-(2-O-apiosylglucoside) (6.8%). The antioxidant activity of Ajuga iva extracts was evaluated by three methods (DPPH*, FRAP, CAT). The hydroethanolic extract recorded the strongest reducing power: DPPH* (IC 50 = 59.92 ± 0.7 µg/mL), FRAP (EC 50 = 196.85 ± 1.54 (µg/mL), and CAT (199.21 ± 0.37 mg EAG/gE). A strong correlation between phenolic compounds and antioxidant activities was confirmed by the determination of Pearson's coefficient. The antimicrobial activity of Ajuga iva studied by the microtiter method revealed potent antifungal and antibacterial qualities against Candida parapsilosis and Staphylococcus aureus BLACT. An in vivo oral glucose tolerance test (OGTT) using normal rats revealed that the antihyperglycemic action of the aqueous extract significantly reduced postprandial hyperglycaemia at (30 min, p < 0.01) and area under the curve (AUC glucose), p < 0.01. Similarly, the aqueous extract, tested on pancreatic α-amylase enzyme activity in vitro and in vivo significantly inhibited pancreatic α-amylase activity with IC 50 = 1.52 ± 0.03 mg/mL. In conclusion, the extract from Ajuga iva could be a good source of bioactive molecules, which exhibit potent antioxidant and antimicrobial activity, as well as strong antidiabetic activity, for applications in the pharmaceutical industry.

Introduction: The Tanacetum genus consists of 160 accepted flowering species thriving throughout temperate regions, mainly in the Mediterranean Basin, Northern America, and southwestern and eastern Asia. Tanacetum species bear a long-standing record of use in the folk medicine of indigenous tribes and communities worldwide, along with multitudinous applications in traditional cuisines, cosmeceuticals, and agricultural fields. Methods: Up-to-date data related to traditional uses, phytochemistry, biological activities, toxicity and clinical trials of the genus Tanacetum were systematically reviewed from several online scientific engines, including PubMed, Web of Science, Scopus, SciFinder, Wiley Online, Science Direct, and Cochrane library. Results and discussion: Over the past three decades, 241 metabolites have been isolated from nearly twenty species, including phenolic acids, flavonoids, coumarins, fatty acids and alkanes, aldehydes, volatile compounds, and naphthoquinones. Some unique metabolites have also been identified, such as the ceramides tanacetamide (A-D) from T. artemisioides , pyrethrins from T. cinerariifolium , and sesquiterpene lactones from several species. However, these secondary metabolites are still poorly studied despite in vitro clues highlighting their colossal pharmacological properties, especially as hypotensive, neuroprotective, anticancer, and antimicrobial agents. Scientific studies have validated some traditional claims of the plant, such as antidiabetic, anticancer, anthelmintic, insecticide, antioxidant, and hepatoprotective activities, as well as against festering wounds, skin ulcers, urinary tract infections, and sexually transmitted diseases. Other ethnomedicinal uses for arthritis, gout, rheumatism, anemia, and as a litholytic, antivenom and diaphoretic have not yet been supported and would constitute the subject of further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Khatib, Sobeh, Faraloni and Bouissane.)

In this work, we have investigated the one pot strategy for the Cu(I)-mediated synthesis of new triazoles bearing nitroindazole moieties using different copper catalysts. The biological activity of newly synthesized nitroindazolyltriazoles towards Alzheimer's disease-related targets, namely cholinesterases, monoamine oxidases, and amyloid aggregation, were investigated. Predictions of target affinity, physicochemical parameters, gastrointestinal absorption and brain penetration were achieved by means of in silico tools., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Sydnones are among the most well-known mesoionic compounds. Since their synthesis in 1935 by Earl and Mecknay, numerous researches have shown that the chemical behavior, physical and biological properties of sydnones make them the most useful compounds in organic chemistry. Sydnones undergo thermal 1,3-dipolar cycloaddition reaction with dipolarophiles (alkynes or alkenes) to give exclusively derivatives containing a pyrazole moiety exhibiting numerous applications, such as pharmaceuticals and agrochemicals. However, the sydnone cycloaddition reaction with alkynes requires harsh conditions, like high temperatures and long reaction times, giving poor regioselectivity to the resulting products. To overcome these constraints, new reactions named CuSAC (Copper- Catalyzed Sydnone-Alkyne Cycloaddition) and SPSAC (Strain-Promoted Sydnone- Alkyne Cycloaddition) have been developed, leading to pyrazoles with interesting constant kinetics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this work, polyphenols were extracted from Anacylus clavatus flowers using a hydroethanolic solvent, and the obtained extract was studied for its total phenol and flavonoid contents and evaluated for its antioxidant and antibacterial capacities. The contents of total phenols and flavonoids were measured by employing gallic acid and quercetin as references, respectively, and the phenolic composition analysis was conducted using high-performance liquid chromatography combined with a photodiode array and electrospray ionization mass spectrometry (HPLC-PDA/ESI-MS). The antioxidant capacity of the extracts was tested using a potassium ferric reducing antioxidant power (PFRAP) assay, and the antibacterial activity assay was carried out against Gram-negative bacteria ( Escherichia coli and Salmonella typhimirium ) and Gram-positive bacteria ( Staphyloccocus aureus and Listeria monocytogenes ) using the broth microdilution assay. The phenolic and flavonoid contents of the extracts equaled 9.53 ± 0.48 mg GAE/g dm and 1.31 ± 0.06 mg QE/g dm, respectively. The chromatographic analysis of the phenolic profile detected 26 phenolic compounds belonging to phenolic acids, flavones and flavonols, and with the caffeoylquinic acid derivatives being the major phenolic compounds present in 12 isomers. Only one organic compound, viz. citric acid, was found. The extracts exhibited interesting antioxidant activity. Bacteriostatic activity towards Escherichia coli and bactericidal activity against Salmonella typhimirium , Staphyloccocus aureus and Listeria monocytogenes were determined. This study revealed that Anacyclus clavatus flower extracts contain phenolic compounds with interesting bioactivities.

Piper cubeba L.f. (Piperaceae), known as cubeb, is a popular traditional herbal medicine used for the treatment of many diseases, especially digestive and respiratory disorders. The plant is rich in essential oil, found mainly in fruits, and this makes it economically important. Many traditional utilizations have been also validated from the plant and its isolated compounds owing to their antioxidant, antibacterial, anti-inflammatory and anticancer effects. These biological activities are attributed to the phytochemicals (phenolic compounds, lignans and alkaloids) and the essential oil of the plant. The present work aims to provide an up-to-date review on the traditional uses, phytochemistry and pharmacology of the plant and discusses the future perspectives to promote its valorization for nutritional- and health-promoting effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Drissi, Mahdi, Yassir, Ben Bakrim, Bouissane and Sobeh.)

Tetraclinis articulata (Vahl) Masters, commonly known as Sandarac tree and Araâr, is the only species representing the genus Tetraclinis Masters. The plant has been extensively used for medicinal, artistic, and ritual purposes since its first recorded use in 1800 B.C. Recently, a full range of ethnobotanical investigations has been undertaken to document the plant's empirical knowledge. They reported the use of different parts, such as leaves, stems, cones, bark, and roots, as part of folk healing practices to manage diabetes mellitus, hypertension, fever, stomach disorders, and diarrhea, among others. The phytochemical studies have identified at least 130 compounds from leaves, cones, resin, bark, and woods. These chemical constituents are categorized into phenolic acids, flavonoids and their derivatives, volatile compounds, phytosterols, and fatty acids, among others. Furthermore, they have strongly been correlated with the promising antimicrobial, antioxidant, neuroprotective, antiurolithiatic, anti-inflammatory, antidiabetic, and cytotoxic properties of the plant. Toxicological studies argued that the plant is quite safe and devoid of eventual toxicity; however, in-depth investigations are required to validate the safety of the plant. The remarkable antimicrobial and antioxidant potencies of various extracts from the plant against a wide range of foodborne pathogens support their possible use to increase the shelf life of foodstuffs in the food industry. Likewise, various plant-based extracts have been proven to exert substantial biocidal properties, making them potential alternatives to synthetic pesticides in agriculture. The present review provides an up-to-date comprehensive insight about the ethnobotanical uses of T. articulata , along with its phytochemistry and biological activities to furnish directions for further studies. We also discussed the biocidal potency of the plant and highlighted its usage to extend the shelf life of perishable foods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khatib, Sobeh and Bouissane.)

Euphorbia resinifera latex has been extensively utilized in traditional medicine due to its range of bioactivities. Chromatographic separations on silica gel of ethanol extract of E. resinifera latex led to the development of a new procedure for isolating resiniferatoxin ( 4 ) via dried E. resinifera latex and the identification of nine compounds. Among these, catechol ( 7 ), protocatechuic acid ( 8 ) and 3,4-dihydroxyphenylacetic acid ( 9 ), known phenolic compounds, were identified for the first time in E. resinifera latex. Herein we investigated the effects of major compounds of the latex of E. resinifera on the yeast Saccharomyces cerevisiae , on the growth of Aspergillus carbonarius , a widespread fungal contaminant, and on the breast cancer cell line MCF7 as well as on MCF10A normal breast cells. 12-deoxyphorbol-13-isobutyrate-20-acetate ( 2 ) had an inhibiting effect on the growth of A. carbonarius , and 7- p -metoxyphenylacetate-3,8,12-triacetate ingol ( 3 ) showed a negative effect on yeast cell growth and also a cytotoxic effect on breast cancer cell line MCF7, but not on MCF10A cells. Deglucosyl euphorbioside A ( 5 ) and euphorbioside A ( 6 ) showed a discoloration effect that was possibly related to mitochondrial functionality in yeast, and also cytotoxicity only on the cancer cell line that was tested. Interestingly, treatment of MCF7 cells with 7- p -metoxyphenylacetate-3,8,12-triacetate ingol ( 3 ) and deglucosyl euphorbioside A ( 5 ) not only led to a specific cytotoxic effect but also to the increase in the level of intracellular ROS., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results

Origanum compactum belonging to the family Lamiaceae is widely used in food and pharmaceutical fields due to its biologically active substances. We aimed to investigate the total phenol and flavonoid contents and the phenolic composition, and to evaluate the antioxidant and antibacterial properties of hydroethanolic extract from of Origanum compactum . Total phenol and flavonoid contents were evaluated using gallic acid and quercetin as standards, respectively, and the phenolic profile was characterized using high-performance liquid chromatography coupled to a photodiode array and electrospray ionization mass spectrometry (HPLC-PDA-ESI/MS). The antioxidant activity was determined by two methods: ferric reducing power (FRAP) assay and the phosphomolybdate method. The antibacterial effect was evaluated against four bacteria ( Escherichia coli , Salmonella typhimurium , Staphylococcus aureus and Listeria monocytogenes ) using the broth microdilution method. The findings show that the total phenolic and flavonoid contents were 107.789 ± 5.39 mg GAE/g dm and 14,977 ± 0.79 mg QE/g dm, respectively. A total of sixteen phenolic compounds belonging to phenolic acids and flavonoids were detected. Furthermore, the extract showed strong antioxidant activity, and displayed a bacteriostatic effect against Escherichia coli and Salmonella typhimuriumn , and a bactericidal effect against Staphylococcus aureus and Listeria monocytogenes . Therefore, this study reveals that Origanum compactum extracts display potential as antibacterial and natural antioxidant agents for fighting against pathogenic bacteria and preventing oxidative stress.

The genus Iris from the Iridaceae family consists of more than 262 recognized species. It is an ornamental and medicinal plant widely distributed in the Northern Hemisphere. Iris species convey a long history as valuable traditional drugs with a wide variety of applications in various cultures, having been recorded since medieval times. Currently, Iris spp. still find application in numerous fields, including cosmetics, pharmaceutics and the food industry. Moreover, many of their empirical uses have been validated by in vitro and in vivo studies, showing that Iris spp. exhibit potent antioxidant, anticancer, anti-inflammatory, hepatoprotective, neuroprotective and anti-microbial properties. Phytochemicals investigations have revealed that the plant extracts are rich in phenolic compounds, especially flavonoids and phenolic acids. As such, they constitute a promising lead for seeking new drugs with high susceptibilities towards various health issues, particularly oxidative-stress-related diseases such as cancers, neurodegenerative diseases, cardiovascular diseases, diabetes, etc. Herein, we present a literature review of the genus Iris intending to determine the plant's chemical profile and establish a coherent overview of the biological applications of the plant extracts with reference to their traditional uses.

N,O-heterocycles containing the dicarbonyl ring play a significant role in heterocyclic and therapeutic chemistry. Since the discovery of 1,3-diketones, numerous research works have been achieved regarding the synthesis and its chemical reactivity. In this review, we have described the most relevant publications involving β-diketone compounds published during the period between 2018 to date. In addition, we include the 1,3-diketones-based heterocyclic compounds prepared by various synthetic methodologies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The synthesis of new porphyrin-indazole hybrids by a Knoevenagel condensation of 2-formyl-5,10,15,20-tetraphenylporphyrin and N-methyl-nitroindazolylacetonitrile derivatives is reported. The target compounds were isolated in moderate to good yields (32-57%) and some of the isolated porphyrin-indazole conjugates showed good performance in the generation of singlet oxygen when irradiated with visible light. Their efficiency as photosensitizers in the photoinactivation of methicillin resistant Staphylococcus aureus-MRSA was evaluated. All derivatives showed to be able to photoinactivate the MRSA bacteria. Compound 3a appears to be the most promising photosensitiser (PS) in the photoinactivation of these bacteria, despite being the least efficient in singlet oxygen generation. The addition of potassium iodide (KI) significantly potentiated the antimicrobial Photodynamic Therapy (aPDT) process mediated by all the analysed porphyrin-indazole conjugates. The combined action of nitroindazole-porphyrins with potassium iodide (KI) action appears to be promising in the photoinactivation of MRSA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The alkylation of a series of nitroindazole derivatives with 1,2-dibromoethane afforded the corresponding N -(2-bromoethyl)- and N -vinyl-nitro-1 H -indazoles. The Cu(I)-catalysed azide- alkyne 1,3-dipolar cycloaddition was selected to substitute the nitroindazole core with 1,4-disubstituted triazole units after converting one of the N -(2-bromoethyl)nitroindazoles into the corresponding azide. The reactivity in 1,3-dipolar cycloaddition reactions with nitrile imines generated in situ from ethyl hydrazono-α-bromoglyoxylates was studied with nitroindazoles bearing a vinyl unit. The corresponding nitroindazole-pyrazoline derivatives were obtained in good to excellent yields.

In the title compound, C19H20ClN3O4S, the benzene ring is inclined to the indazole ring system (r.m.s. deviation = 0.014 Å) by 65.07 (8)°. The allyl and eth-oxy groups are almost normal to the indazole ring, as indicated by the respective torsion angles [N-N-C-C = 111.6 (2) and C-C-O-C = -88.1 (2)°]. In the crystal, mol-ecules are connected by N-H⋯N hydrogen bonds, forming helical chains propagating along [010]. The chains are linked by C-H⋯O hydrogen bonds, forming a three-dimensional network.

Some new N-[6-indazolyl]arylsulfonamides and N-[alkoxy-6-indazolyl]arylsulfonamides were prepared by the reduction of 2-alkyl-6-nitroindazoles with SnCl2 in different alcohols, followed by coupling the corresponding amine with arylsulfonyl chlorides in pyridine. The newly synthesized compounds were evaluated for their antiproliferative and apoptotic activities against two human tumor cell lines: A2780 (ovarian carcinoma) and A549 (lung adenocarcinoma). Preliminary in vitro pharmacological studies revealed that N-(2-allyl-2H-indazol-6-yl)-4-methoxybenzenesulfonamide 4 and N-[7-ethoxy-2-(4-methyl-benzyl)-2H-indazol-6-yl]-4-methyl-benzenesulfonamide 9 exhibited significant antiproliferative activity against the A2780 and A549 cell lines with IC50 values in the range from 4.21 to 18.6 µM, and also that they trigger apoptosis in a dose-dependent manner. Furthermore, both active compounds were able to cause an arrest of cells in the G2/M phase of the cell cycle, typical but not exclusive of tubulin interacting agents, although only infrequent interactions with the microtubule network were observed by immunofluorescence microscopy, while docking analysis showed a possible different behavior between the two active compounds., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In the title compound, C19H20ClN3O3S, the benzene ring is inclined to the indazole ring system by 51.23 (8)°. In the crystal, mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming inversion dimers which stack in columns parallel to [011]. The atoms in the allyl group are disordered over two sets of sites with an occupancy ratio of 0.624 (8):0.376 (8).

The indazole ring system of the title compound, C19H21N3O3S, is almost planar (r.m.s. deviation = 0.0192 Å) and forms dihedral angles of 77.99 (15) and 83.9 (3)° with the benzene ring and allyl group, respectively. In the crystal, centrosymmetrically related mol-ecules are connected by pairs of N-H⋯O hydrogen bonds into dimers, which are further linked by C-H⋯O hydrogen bonds, forming columns parallel to the b axis.

In the title compound, C14H13N3O3S, the fused ring system is almost planar, the largest deviation from the mean plane being 0.023 (2) Å, and makes a dihedral angle of 47.92 (10)° with the benzene ring of the benzene-sulfonamide moiety. In the crystal, mol-ecules are connected through N-H⋯O hydrogen bonds and weak C-H⋯O contacts, forming a two-dimensional network which is parallel to (010).

In the title compound, C14H12ClN3O3S, the fused five- and six-membered rings are folded slightly along the common edge, forming a dihedral angle of 3.2 (1)°. The mean plane through the indazole system makes a dihedral angle of 30.75 (7)° with the distant benzene ring. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules, forming a two-dimensional network parallel to (001).

A new ZnPc-PDI dyad presenting for the first time a charge-separated state lower in energy than the triplet excited state of the ZnPc and PDI has been synthesized. The rational design implies the substitution of the ZnPc with phenoxy groups and the bay substitution of the PDI with sulfonyl substituents. The lifetime of the charge-separated state was 72 μs.

Unsymmetrical 3,4-disubstituted maleimides have been synthesized by palladium-catalyzed cross-coupling reactions of indium organometallics with 3,4-dihalomaleimides. The synthesis was performed by stepwise or sequential one-pot palladium-catalyzed cross-coupling reactions with various triorganoindium reagents. This method was used to prepare a wide variety of alkyl, aryl, heteroaryl, and alkynyl 3,4-disubstituted maleimides in good yields and with high selectivity and atom economy.

Seven N-unsubstituted curcuminoid pyrazoles have been synthesized from the corresponding beta-diketones (including curcumin). We evaluated the possibility of curcuminoid pyrazoles regulating the activity of matrix metalloproteinases (MMPs) by human intestinal epithelial cells in vitro. Zymographic analysis revealed that three compounds significantly down-regulated MMP-9 activity on inflammation-induced intestinal epithelial cells, making them original candidates for the treatment of inflammatory bowel disease (IBD).

We herein describe a new synthesis of N-(7-indazolyl)benzenesulfonamide derivatives. These compounds were evaluated for their antiproliferative activities toward L1210 murine leukemia cells. One of them, 4-methoxy-N-(3-chloro-7-indazolyl)benzenesulfonamide, was identified as the most potent with an IC(50) of 0.44 microM.