Quinazolin‐4(3H)‐one‐Based Hydroxamic Acids: Design,Synthesis and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity

The present article describes the synthesis and biological activity of various series of novel hydroxamic acids incorporating quinazolin‐4(3H)‐ones as novel small molecules targeting histone deacetylases. Biological evaluation showed that these hydroxamic acids were potently cytotoxic against three human cancer cell lines (SW620, colon; PC‐3, prostate; NCI?H23, lung). Most compounds displayed superior cytotoxicity than SAHA (suberoylanilide hydroxamic acid, Vorinostat) in term of cytotoxicity. Especially, N‐hydroxy‐7‐(7‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5b ) and N‐hydroxy‐7‐(6‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5c ) (IC₅₀ values, 0.10–0.16 μm ) were found to be approximately 30‐fold more cytotoxic than SAHA (IC₅₀ values of 3.29–3.67 μm ). N‐Hydroxy‐7‐(4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5a ; IC₅₀ values of 0.21–0.38 μm ) was approximately 10‐ to 15‐fold more potent than SAHA in cytotoxicity assay. These compounds also showed comparable HDAC inhibition potency with IC₅₀ values in sub‐micromolar ranges. Molecular docking experiments indicated that most compounds, as represented by 5b and 5c , strictly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA.     

New Acetohydrazides Incorporating 2‐Oxoindoline and 4‐Oxoquinazoline: Synthesis and Evaluation of Cytotoxicity and Caspase Activation Activity

In our search for new small molecules activating procaspase‐3, we have designed and synthesized a series of new acetohydrazides incorporating both 2‐oxoindoline and 4‐oxoquinazoline scaffolds. Biological evaluation showed that a number of these acetohydrazides were comparably or even more cytotoxic against three human cancer cell lines (SW620, colon cancer; PC‐3, prostate cancer; NCI?H23, lung cancer) in comparison to PAC‐1, a first procaspase‐3 activating compound, which was used as a positive control. One of those new compounds, 2‐(6‐chloro‐4‐oxoquinazolin‐3(4H)‐yl)‐N′‐[(3Z)‐5‐methyl‐2‐oxo‐1,2‐dihydro‐3H‐indol‐3‐ylidene]acetohydrazide activated the caspase‐3 activity in U937 human lymphoma cells by 5‐fold higher than the untreated control. Three of the new compounds significantly induced necrosis and apoptosis in U937 cells.     

Chemical Characteristics,Antimicrobial, and Cytotoxic Activities of the Essential Oil of Egyptian Cinnamomum glanduliferum Bark

The essential oil isolated from the bark of Cinnamomum glanduliferum (Wall ) Meissn grown in Egypt was screened for its composition as well as its biological activity for the first time. The chemical composition was analyzed by GC and GC/MS. The antimicrobial activity of the oil was assessed using agar‐well diffusion method toward representatives for each of Gram‐positive bacteria, Gram‐negative bacteria, and fungi. The cytotoxic activity was checked using three human cancer cell lines. Twenty seven compounds were identified, representing 99.07% of the total detected components. The major constituents were eucalyptol (65.87%), terpinen‐4‐ol (7.57%), α‐terpineol (7.39%). The essential oil possessed strong antimicrobial activities against Escherichia coli, with an activity index of one and minimum inhibitory concentration (MIC) equaling to 0.49 μg/ml. The essential oil possessed good antimicrobial activities against methicillin‐resistant Staphylococcus aureus, Geotrichum candidum, Pseudomonas aeruginosa, Bacillus subtilis, Helicobacter pylori, Aspergillus fumigatus (MIC: 7.81, 1.95, 7.81, 0.98, 31.25, and 32.5 μg/ml, respectively). A considerable activity was reported against S. aureus and Mycobacterium tuberculosis (MIC; 32.5 and 31.25 μg/ml, respectively). The extracted oil was cytotoxic to colon (HCT‐116), liver (HepG2), and breast (MCF‐7) carcinoma cell lines with IC₅₀ of 9.1, 42.4, and 57.3 μg/ml, respectively. These results revealed that Egyptian Cinnamomum glanduliferum bark oil exerts antimicrobial and cytotoxic activities mainly due to eucalyptol and other major compounds.     

Design,Synthesis and Bioevaluation of Two Series of 3‐[(1‐Benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐ones and N‐(1‐Benzylpiperidin‐4‐yl)quinazolin‐4‐amines

Two series of 3‐[(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐ones and N‐(1‐benzylpiperidin‐4‐yl)quinazolin‐4‐amines were designed initially as potential acetylcholine esterase inhibitors. Biological evaluation demonstrated that N‐(1‐benzylpiperidin‐4‐yl)quinazolin‐4‐amines significantly inhibited AChE activity. Especially, two compounds of them were found to be the most potent with relative AChE inhibition percentages of 87 % in comparison to donepezil. The docking studies with AChE showed similar interactions between donepezil and four derivatives. N‐(1‐Benzylpiperidin‐4‐yl)quinazolin‐4‐amines also exhibited significant DPPH scavenging effects. The two series of compound also exerted moderate to good cytotoxicity against three human cancer cell lines, including SW620 (human colon cancer), PC‐3 (prostate cancer), and NCI?H23 (lung cancer), with 3‐[(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐one being the most cytotoxic agent. 3‐[(1‐Benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐one significantly induced early apoptosis and arrested the SW620 cells at G2/M phase. From this study, two compounds of N‐(1‐benzylpiperidin‐4‐yl)quinazolin‐4‐amines could serve as new leads for further design and AChE inhibitors, while 3‐[(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐one could serve as a new lead for the design and development of more potent anticancer agents.     

Chemical composition and antimicrobial activity of volatiles from Degenia velebitica, a European stenoendemic plant of the Brassicaceae family

Free and glucosidic bound leaf volatiles of Degenia velebitica were isolated and fractionated simultaneously into H₂O‐soluble, H₂O‐insoluble, and highly volatile compounds by hydrodistillation–adsorption (HDA) and analyzed by GC/MS. Among the 24 constituents identified, the main compounds obtained by the HDA method were S‐ and/or N‐atom containing compounds, i.e., 6‐(methylsulfanyl)hexanenitrile ( 10 ; 26.78%), dimethyl trisulfide ( 6 ; 26.35%), 3,4,5‐trimethylpyrazole ( 17 ; 13.33%), hex‐5‐enenitrile ( 2 ; 10.11%), dimethyl tetrasulfide ( 8 ; 4.93%), and pent‐4‐enyl isothiocyanate ( 7 ; 4.45%). In addition, O‐glycosidically bound volatiles and free volatiles were isolated by solvent extraction. Sixteen volatile O‐aglycones and twelve free volatile components were identified. The main O‐aglycones were eugenol ( 19 ; 24.15%), 2‐methoxy‐4‐vinylphenol ( 11 ; 11.50%), and benzyl alcohol ( 20 ; 9.49%), and the main free volatiles were (9Z,12Z)‐octa‐9,12‐dienic acid (38.35%), hexadecanoic acid (22.64%), and phytol (5.80%). The H₂O‐soluble volatile fraction obtained by HDA, containing mostly glucosinolate degradation products and 3,4,5‐trimethylpyrazole ( 17 ), was evaluated for antimicrobial activity by determining inhibition zones with the diffusion method as well as minimal inhibitory concentrations (MIC) and minimal microbicidal concentrations (MMC) with the micro‐dilution method. The fraction expressed activity against the tested Gram‐positive and Gram‐negative bacteria as well as against yeast, with MIC values equal to or lower than 16.7 μg/ml.     

Hybrid Pharmacophoric Approach in the Design and Synthesis of Coumarin Linked Pyrazolinyl as Urease Inhibitors,Kinetic Mechanism and Molecular Docking

The current research article reports the synthesis of coumarinyl pyrazolinyl thioamide derivatives and their biological activity as inhibitors of jack bean urease. The coumarinyl pyrazolinyl thioamides were synthesized by reacting thiosemicarbazide with newly synthesized chalcones to afford the products in good yields and the synthesized compounds were purified by recrystallization. Coumarinyl pyrazolinyl thioamide derivatives 5a  –  5q showed significant activity against Urease enzyme and also exhibited good antioxidant potential. The compound 3‐(2‐oxo‐2H‐chromen‐3‐yl)‐5‐phenyl‐4,5‐dihydro‐1H‐pyrazole‐1‐carbothioamide ( 5n ) was found to be superior agent in the series with an IC₅₀ = 0.358 ± 0.017 μm compared to standard thiourea with an IC₅₀ = 4720 ± 174 μm . To undermine the binding mode of inhibition kinetic studies were performed for most potent derivative and it was found that compound 5n inhibits urease enzyme by non‐competitive mode of inhibition. Molecular docking studies were carried out to delineate the binding affinity of the synthesized derivatives.     

Synthesis and Anticancer Activity of 3‐(Substituted Aroyl)‐4‐(3,4,5‐trimethoxyphenyl)‐1H‐pyrrole Derivatives

A series of 3‐(substituted aroyl)‐4‐(3,4,5‐trimethoxyphenyl)‐1H‐pyrrole derivatives were synthesized and determined for their anticancer activity against eleven cancer cell lines and two normal tissue cell lines using MTT assay. Among the synthesized compounds, compound 3f was the most potent compound against A375, CT‐26, HeLa, MGC80‐3, NCI‐H460 and SGC‐7901 cells (IC₅₀ = 8.2 – 31.7 μm ); 3g , 3n and 3a were the most potent compounds against CHO (IC₅₀ = 8.2 μm ), HCT‐15 (IC₅₀ = 21 μm ) and MCF‐7 cells (IC₅₀ = 18.7 μm ), respectively. Importantly, all the target compounds showed no cytotoxicity towards the normal tissue cell (IC₅₀ > 100 μm ). Thus, these compounds with the potent anticancer activity and low toxicity have potential for the development of new anticancer chemotherapy agents.     

Antimicrobial and Cytotoxic Activity of Extracts of Ferula heuffelii Griseb. ex Heuff. and Its Metabolites

The antimicrobial and cytotoxic activities of isolates (CHCl₃ and MeOH extracts and selected metabolites) obtained from the underground parts of the Balkan endemic plant Ferula heuffelii Griseb . ex Heuff . were assessed. The CHCl₃ and MeOH extracts exhibited moderate antimicrobial activity, being more pronounced against Gram‐positive than Gram‐negative bacteria, especially against Staphylococcus aureus (MIC=12.5 μg/ml for both extracts) and Micrococcus luteus (MIC=50 and 12.5 μg/ml, resp.). Among the tested metabolites, (6E)‐1‐(2,4‐dihydroxyphenyl)‐3,7,11‐trimethyl‐3‐vinyldodeca‐6,10‐dien‐1‐one ( 2 ) and (2S*,3R*)‐2‐[(3E)‐4,8‐dimethylnona‐3,7‐dien‐1‐yl]‐2,3‐dihydro‐7‐hydroxy‐2,3‐dimethylfuro[3,2‐c]coumarin ( 4 ) demonstrated the best antimicrobial activity. Compounds 2 and 4 both strongly inhibited the growth of M. luteus (MIC=11.2 and 5.2 μM , resp.) and Staphylococcus epidermidis (MIC=22.5 and 10.5 μM , resp.) and compound 2 additionally also the growth of Bacillus subtilis (MIC=11.2 μM ). The cytotoxic activity of the isolates was tested against three human cancer cell lines, viz., cervical adenocarcinoma (HeLa), chronic myelogenous leukemia (K562), and breast cancer (MCF‐7) cells. The CHCl₃ extract exhibited strong cytotoxic activity against all cell lines (IC₅₀<11.0 μg/ml). All compounds strongly inhibited the growth of the K562 and HeLa cell lines. Compound 4 exhibited also a strong activity against the MCF‐7 cell line, comparable to that of cisplatin (IC₅₀=22.32±1.32 vs. 18.67±0.75μM ).     

Indole Alkaloids from the Sea Anemone Heteractis aurora and Homarine from Octopus cyanea

The two new indole alkaloids 2‐amino‐1,5‐dihydro‐5‐(1H‐indol‐3‐ylmethyl)‐4H‐imidazol‐4‐one ( 1 ), 2‐amino‐5‐[(6‐bromo‐1H‐indol‐3‐yl)methyl]‐3,5‐dihydro‐3‐methyl‐4H‐imidazol‐4‐one ( 2 ), and auramine ( 3 ) have been isolated from the sea anemone Heteractis aurora. Both indole alkaloids were synthesized for the confirmation of the structures. Homarine ( 4 ), along with uracil ( 5 ), hypoxanthine ( 6 ), and inosine ( 7 ) have been obtained from Octopus cyanea.     

Design and Synthesis of Novel Cytotoxic Indole‐Thiosemicarbazone Derivatives: Biological Evaluation and Docking Study

In this work, two novel series of indole‐thiosemicarbazone derivatives were designed, synthesized, and evaluated for their cytotoxic activity against MCF‐7, A‐549, and Hep‐G2 cell lines in comparison to etoposide and colchicine as the reference drugs. Generally, the synthesized compounds showed better cytotoxicity towards A‐549 and Hep‐G2 than MCF‐7. Among them, (2E)‐2‐{[2‐(4‐chlorophenyl)‐1H‐indol‐3‐yl]methylidene}‐N‐(4‐methoxyphenyl)hydrazinecarbothioamide ( 8l ) was found to be the most potent compound against A‐549 and Hep‐G2, at least three times more potent than etoposide. The morphological analysis by the acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that compound 8l induced apoptosis in A‐549 cells. Moreover, molecular docking methodology was exploited to elucidate the details of molecular interactions of the studied compounds with putative targets.     

Chemical Composition,Antioxidant Properties, α‐Glucosidase Inhibitory,and Antimicrobial Activity of Essential Oils from Acacia mollissima and Acacia cyclops Cultivated in Tunisia

The genus Acacia is quite large and can be found in the warm subarid and arid parts, but little is known about its chemistry, especially the volatile parts. The volatile oils from fresh flowers of A. mollissima and A. cyclops (growing in Tunisia) obtained by hydrodistillation were analyzed by GC then GC/MS. Eighteen (94.7% of the total oil composition) and 23 (97.4%) compounds were identified in these oils, respectively. (E,E)‐α‐Farnesene (51.5%) and (E)‐cinnamyl alcohol (10.7%) constituted the major compounds of the flower oil of A. mollissima, while nonadecane (29.6%) and caryophyllene oxide (15.9%) were the main constituents of the essential oil of A. cyclops. Antioxidant activity of the isolated oils was studied by varied assays, i.e., 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and 2,2‐azinobis 3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS); the isolated oils showed lowest IC₅₀ (4 – 39 μg/ml) indicating their high antioxidant activity. The α‐glucosidase inhibitor activity was also evaluated and Acacia oils were found to be able to strongly inhibit this enzyme with IC₅₀ values (81 – 89 μg/ml) very close to that of acarbose which was used as positive control. Furthermore, they were tested against five Gram‐positive and Gram‐negative bacteria and one Candida species. Essential oil of A. mollissima was found to be more active than that of A. cyclops, especially against Pseudomonas aeruginosa (MIC = 0.31 mg/ml and MBC = 0.62 mg/ml).     

New Furanone Derivatives and Alkaloids from the Co‐Culture of Marine‐Derived Fungi Aspergillus sclerotiorum and Penicillium citrinum

Six new compounds including two furanone derivatives sclerotiorumins A and B ( 1 and 2 ), one novel oxadiazin derivative sclerotiorumin C ( 3 ), one pyrrole derivative 1‐(4‐benzyl‐1H‐pyrrol‐3‐yl)ethanone ( 4 ), and two complexes of neoaspergillic acid aluminiumneohydroxyaspergillin ( 5 ) and ferrineohydroxyaspergillin ( 6 ) were isolated from the co‐culture of marine‐derived fungi Aspergillus sclerotiorum and Penicillium citrinum. Compound 3 was the first natural 1,2,4‐oxadiazin‐6‐one. Compound 5 showed significant and selective cytotoxicity against human histiocytic lymphoma U937 cell line (IC₅₀ = 4.2 μm ) and strong toxicity towards brine shrimp (LC₅₀ = 6.1 μm ), and oppositely increased the growth and biofilm formation of Staphylococcus aureus.     

Inhibitory Activity and Chemical Characterization of Daucus carota subsp. maximus Essential Oils

The essential oils (EOs) of green seeds from Daucus carota subsp. maximus growing wild in Pantelleria Island (Sicily, Italy) were characterized. EOs were extracted by steam distillation, examined for their inhibitory properties against food‐borne Gram‐positive and Gram‐negative bacteria and analyzed for the chemical composition by gas chromatography (GC) and mass spectrometry (MS). Undiluted EOs showed a large inhibition spectrum against Gram‐positive strains and also vs. Acinetobacter spp. and Stenotrophomonas maltophilia. The minimum inhibition concentration (MIC) was in the range 1.25 – 2.50 μl/ml for the most sensitive strains. The chemical analysis indicated that D. carota subsp. maximus EOs included 34 compounds (five monoterpene hydrocarbons, six oxygenated monoterpenes, 14 sesquiterpene hydrocarbons, four oxygenated sesquiterpenes, camphorene and four other compounds), accounting for 95.48% of the total oil, and that the major chemicals were carotol, β‐bisabolene, and isoelemicin.     

Chemical Composition and In Vitro Evaluation of Antimicrobial,Antioxidant and Antigerminative Properties of the Seed Oil from the Tunisian Endemic Ferula tunetana Pomel ex Batt.

Essential oil of the seeds from the endemic Tunisian plant Ferula tunetana Pomel ex Batt . was analyzed for its chemical composition and screened for its antimicrobial, antioxidant and antigerminative properties. The chemical composition of the isolated oil is reported for the first time. According to the GC/FID, GC/MS and ¹³C‐NMR analysis results; 18 compounds were identified accounting for 84.6% of the total oil. The chemical composition of this essential oil was characterized by the presence of a high proportion of monoterpene hydrocarbons (77.3%) followed by oxygenated sesquiterpenes (4.1%) and sesquiterpene hydrocarbons (3.2%). α‐Pinene (39.8%), β‐pinene (11.5%) and (Z)‐β‐ocimene (7.5%) were the predominant compounds. Moreover, the isolated oil was tested for its antimicrobial activity using the disc‐diffusion and the microdilution assays against six Gram‐positive and five Gram‐negative bacteria as well as towards two Candida species. The isolated oil was tested also for its antioxidant activity against DPPH, ABTS, and hydrogen peroxide (H₂O₂), and for its antigerminative potential. It was found that it exhibited interesting antimicrobial activity against Salmonella typhimurium LT2 DT104 (inhibition zone (IZ) 16.2 ± 1.0 mm) and Bacillus cereus ATCC 14579 (IZ 15.8 ± 1.0 mm). However, it exerted a moderate antioxidant activity against H₂O₂ (IC₅₀ 78.2 ± 2.98 μg/ml) and towards (IC₅₀ 89.2 ± 3.82 μg/ml). The antigerminative effect of this oil was also evaluated in this work. Results showed a toxic effect.     

Synthesis,Characterization and Evaluation of Cytotoxic Activities of Novel Aziridinyl Phosphonic Acid Derivatives

New aziridine 2‐phosphonic acids were prepared by monohydrolysis of the aziridine 2‐phosphonates that were obtained by the modified Gabriel?Cromwell reaction of vinyl phosphonate or α‐tosylvinyl phosphonate with a primary amine or a chiral amine. The cellular cytotoxicity of these compounds was tested against the HCT‐116 colorectal cancer cell lines and the CCD‐18Co normal colon fibroblast lines using the MTT assay. Three of the synthesized phosphonic acid derivatives 2e (ethyl hydrogen {(2S)‐1‐[(1S)‐1‐(naphthalen‐2‐yl)ethyl]aziridin‐2‐yl}phosphonate), 2h (ethyl hydrogen (1‐benzylaziridin‐2‐yl)phosphonate), and 2i (ethyl hydrogen (1‐cyclohexylaziridin‐2‐yl)phosphonate) showed higher cytotoxicity than the reference cancer treatment agent etoposide. Cell death was through a robust induction of apoptosis even more effectively than etoposide, a well‐known apoptosis inducing agent.     

Cytotoxic Compounds from the Leaves of Garcinia polyantha

A new compound, named banganxanthone C (=12‐(1,1‐dimethylprop‐2‐en‐1‐yl)‐5,10‐dihydroxy‐9‐methoxy‐2‐methyl‐2‐(4‐methylpent‐3‐en‐1‐yl)‐2H,6H‐pyrano[3,2‐b]xanthen‐6‐one; 4 ), together with five known compounds, were isolated from the leaves of Garcinia polyantha. The structures of the compounds were elucidated on the basis of 1D‐ and 2D‐NMR spectroscopy. Among the known compounds, two were xanthones, one was a pentacyclic triterpene, one sterol, and one benzophenone derivative. Isoxanthochymol ( 2 ) and 4‐[(2E)‐3,7‐dimethylocta‐2,6‐dien‐1‐yl]‐1,5,8‐trihydroxy‐3‐methoxy‐9H‐xanthen‐9‐one ( 3 ) exhibited significant antiproliferative activity against the leukemia cell line TPH‐1 with IC₅₀ inhibition values of 1.5 and 2.8 μg/ml, respectively. The cytotoxic activity was found to be related to apoptosis induction.     

Chemical Diversity and Antimicrobial Activity of Salvia multicaulis Vahl Essential Oils

The chemical compositions and antimicrobial activities of the essential oils (EOs) of aerial parts of Salvia multicaulis Vahl , collected during the same week from two different Lebanese regions, were investigated. The EOs were obtained by hydrodistillation using a Clevenger‐type apparatus and characterized by GC and GC/MS analyses. The minimum inhibitory concentrations of these EOs were determined against one Gram‐negative and two Gram‐positive bacteria, one yeast, and five dermatophytes using the broth microdilution technique. One EO was notably active against Staphylococcus aureus, methicillin‐resistant S. aureus, and all of the Trichophyton species tested. Nerolidol was found to be the major compound in the active oil; nerolidol was also absent from the inactive oil. This study demonstrated that nerolidol shows antimicrobial activity and therefore significantly contributes to the antimicrobial potential of the oil. The chemical diversity of worldwide S. multicaulis EOs was analyzed, revealing that the EOs of this study belong to two different chemotypes found in the literature. The nerolidol chemotype appears to be restricted to Lebanon, and it can be used as antimicrobial agent against external bacterial and fungal infections.     

Synthesis,Cytotoxic, and Antibacterial Evaluation of Quinazolinone Derivatives with Substituted Amino Moiety

A series of novel quinazolinone derivatives containing a substituted amino moiety were synthesized, evaluated for their cytotoxic and antibacterial activities. The results of MTT assay showed that all synthesized target compounds 5A  –  5O showed potent cytotoxicity against SGC‐7901 (IC₅₀, 0.72 – 1.41 μm ). Moreover, the compounds 5D , 5I , and 5K showed better selectivity as compared with positive controls pemetrexed and MTX due to weak cytotoxicity against normal tissue cell line HUVSMC. Among synthesized compounds, the compounds 5E , 5J , 5L , and 5N showed broad‐spectrum cytotoxic activities against at least four cancer cell lines at a micromolar level. The results of antibacteria evaluation revealed that all synthesized compounds showed good to moderate antibacterial activities against Gram‐negative bacteria Escherichia coli. Among them, the MIC values of the compounds 5C , 5F , and 5M were 0.31 μg/mL.     

Synthesis,Molecular Properties Prediction and Antimicrobial Activity of Imidazolyl Schiff Bases,Triazoles and Azetidinones

Benzylidenehydrazinyl imidazoles ( 3 ) are prepared from 2‐hydrazinyl imidazoles ( 2 ) on treatment with hydrazine. The imine functionality in 3 is utilized to develop 5′‐aryl‐N‐(4‐aryl‐1H‐imidazol‐2‐yl)‐1H‐1,2,3‐triazol‐1‐amines ( 5 ) by 1,3‐dipolar cycloaddition of diazomethane followed by aromatization with I₂ in DMSO. Compounds 3 are also explored to prepare 4′‐aryl‐1‐(4‐aryl‐1H‐imidazol‐2‐ylamino)‐3‐chloroazetidin‐2‐ones ( 6 ) on treatment with chloroacetyl chloride. The Molinspiration calculations predicted that 3 , 5 and 6 have molecular hydrophobicity, conformational flexibility, good intestinal absorption and bioactivity scores. The chloro, bromo and nitro substituted imidazolyl azetidinones ( 6c , 6d , 6f ) and nitro substituted imidazolyl triazole ( 5f ) exhibited excellent antibacterial activity on B. subtilis, whereas chloro and nitro substituted imidazolyl triazoles ( 5c , 5f ) showed prominent antifungal activity on A. niger.     

Cytotoxic and Anti‐inflammatory Sesquiterpenes from Ainsliaea henryi

Three new sesquiterpenoids, 4α‐hydroxyeudesm‐11(13)‐en‐12‐yl 3‐methylbutanoate ( 1 ), diaspanolide E ( 2 ), and (13α)‐germacra‐1(10),4‐dien‐12,8α‐olid‐15‐oic acid ( 3 ), along with eight known sesquiterpenoids ( 4 – 11 ), were isolated from the aerial parts of Ainsliaea henryi. The chemical structures of compounds 1 – 3 were elucidated by spectroscopic analysis (1D‐, 2D‐NMR, MS and HR/MS). All isolates were evaluated for their inhibitory activities against nitric oxide (NO) production in lipopolysaccharide‐induced RAW264.7 macrophage cells. Compound 10 exhibited significantly inhibition against NO release with an IC₅₀ value of 6.54 ± 0.16 μm . Also, all isolated compounds were tested for cytotoxicity against three human tumor cell lines A549, MGC803, and HCT116, among which compound 5 significantly inhibited the proliferation of MGC803 cell lines with an IC₅₀ value of 2.2 ± 0.2 μm .