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Aurora kinases (Aurora A, B, and C) are a family of serine/threonine kinases that play critical roles during mitotic initiation and progression. Aurora A and B kinases are ubiquitously expressed, and their overexpression and/or amplification in many cancers have been associated with poor prognosis. Several inhibitors that target Aurora kinases A, B, or both have been developed during the past decade with efficacy in different in vitro and in vivo models for a variety of cancers. Recent studies have also identified Aurora A as a synthetic lethal target for different tumor suppressors, including RB1, SMARCA4, and ARID1A, which signifies the need for Aurora-A-selective inhibitors. Here, we report the screening of a small library of quinones (nine naphthoquinones, one orthoquinone, and one anthraquinone) in a biochemical assay for Aurora A kinase that resulted in the identification of several quinones as inhibitors. IC

The review introduced chemical diversity in structures, biological activities, biosynthesis and chemical synthesis of unusual cyclized triterpenoids.

Chemical investigation of the aerial parts of Astragalus lehmannianus Bunge (Leguminosae) led to the isolation and identification of a new cycloartane triterpene glycoside – lehmanniaside (2'-O-ace...

Nature continuously produces biologically useful molecules and provides mankind with life-saving drugs or therapies [...]

Yu Zhang,1– 3,* Li Cui,2,* Yizeng Lu,4 Jixiang He,5 Hidayat Hussain,6 Lei Xie,4 Xuan Sun,2 Zhaoqing Meng,7 Guiyun Cao,7 Dawei Qin,1 Daijie Wang2,3 1School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, People’s Republic of China; 2School of Pharmaceutical Sciences and Key Laboratory for Applied Technology of Sophisticated Analytical Instruments of Shandong Province, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250014, People’s Republic of China; 3Biological Engineering Technology Innovation Center of Shandong Province, Heze Branch of Qilu University of Technology (Shandong Academy of Sciences), Heze, 274000, People’s Republic of China; 4Shandong Provincial Center of Forest and Grass Germplasm Resources, Jinan, 250102, People’s Republic of China; 5School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250353, People’s Republic of China; 6Department of Bioorganic Chemistry, Leibniz Institute of Plant BioChemistry, Halle, D-06120, Germany; 7Shandong Hongjitang Pharmaceutical Group Co., Ltd., Jinan, 250103, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dawei Qin, School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, People’s Republic of China, Tel/Fax +86 53189631208, Email qdw@qlu.edu.cn Daijie Wang, Biological Engineering Technology Innovation Center of Shandong Province, Heze Branch of Qilu University of Technology (Shandong Academy of Sciences), Heze, 274000, People’s Republic of China, Tel +86 53182605319, Fax +86 53182964889, Email wangdaijie@qlu.edu.cnBackground: The leaves of L. japonica (LLJ) are widely used as medicine in China. It is rich in caffeoylquinic acids, flavonoids and iridoid glycosides and has strong reducing capacities. Therefore, it can be used as a green material to synthesize silver nanoparticles.Methods: LLJ was used as a reducing agent to produce the LLJ-mediated silver nanoparticles (LLJ-AgNPs). The structure and physicochemical properties of LLJ-AgNPs were characterized by ultraviolet spectroscopy (UV-Vis), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and x-ray powder diffraction (XRD). Antioxidant activity of LLJ-AgNPs was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging. Antibacterial activity was determined by 96 well plates (AGAR) gradient dilution, while the anticancer potential was determined by MTT assay.Results: The results showed LLJ-AgNPs had a spherical structure with the maximum UV-Vis absorption at 400 nm. In addition, LLJ-AgNPs exhibited excellent antioxidant properties, where the free radical scavenging rate of LLJ-AgNPs was increased from 39% to 92% at concentrations from 0.25 to 1.0 mg/mL. Moreover, LLJ-AgNPs displayed excellent antibacterial properties against E. coli and Salmonella at room temperature, with minimum inhibitory values of 10− 6 and 10− 5 g/L, respectively. In addition, the synthetic LLJ-AgNPs exhibited a better inhibition effect in the proliferation of cancer cells (HepG2, MDA-MB − 231, and Hela cells).Conclusion: The present study provides a green approach to synthesize LLJ-AgNPs. All those findings illustrated that the produced LLJ-AgNPs can be used as an economical and efficient functional material for further applications in food and pharmaceutical fields.Keywords: leaves of Lonicera japonica Thunb, LLJ-AgNO3-NPs, green approach, antioxidant, antibacterial, anticancer

Activating mutations in FLT3 receptor tyrosine kinase are found in a third of acute myeloid leukemia (AML) patients and are associated with disease relapse and a poor prognosis. The majority of these mutations are internal tandem duplications (ITDs) in the juxtamembrane domain of FLT3, which have been validated as a therapeutic target. The clinical success of selective inhibitors targeting oncogenic FLT3, however, has been limited due to the acquisition of drug resistance. Herein the identification of a dual FLT3/microtubule polymerization inhibitor, chalcone 4 (2'-allyloxy-4,4'-dimethoxychalcone), is reported through screening of 15 related chalcones for differential antiproliferative activity in leukemia cell lines dependent on FLT3-ITD (MV-4-11) or BCR-ABL (K562) oncogenes and by subsequent screening for mitotic inducers in the HCT116 cell line. Three natural chalcones (1-3) were found to be differentially more potent toward the MV-4-11 (FLT3-ITD) cell line compared to the K562 (BCR-ABL) cell line. Notably, the new semisynthetic chalcone 4, which is a 2'-O-allyl analogue of the natural chalcone 3, was found to be more potent toward the FLT3-ITD+ cell line and inhibited FLT3 signaling in FLT3-dependent cells. An in vitro kinase assay confirmed that chalcone 4 directly inhibited FLT3. Moreover, chalcone 4 induced mitotic arrest in these cells and inhibited tubulin polymerization in both cellular and biochemical assays. Treatment of MV-4-11 cells with this inhibitor for 24 and 48 h resulted in apoptotic cell death. Finally, chalcone 4 was able to overcome TKD mutation-mediated acquired resistance to FLT3 inhibitors in a MOLM-13 cell line expressing FLT3-ITD with the D835Y mutation. Chalcone 4 is, therefore, a promising lead for the discovery of dual-target FLT3 inhibitors.

Green synthesis of silver nanoparticles (AgNPs) employing an aqueous plant extract has emerged as a viable eco-friendly method. The aim of the study was to synthesize AgNPs by using plant extract of Sanvitalia procumbens (creeping zinnia) in which the phytochemicals present in plant extract act as a stabilizing and reducing agent. For the stability of the synthesized AgNPs, different parameters like AgNO3 concentration, volume ratios of AgNO3, temperature, pH, and contact time were studied. Further, AgNPs were characterized by UV–visible spectroscopy, FT-IR (Fourier Transform Infrared Spectroscopy), XRD (X-ray Diffraction), SEM (Scanning Electron Microscopy), and EDX (Energy Dispersive X-ray Spectrometer) analysis. FT-IR analysis showed that the plant extract contained essential functional groups like O–H stretching of carboxylic acid, N–H stretching of secondary amides, and C–N stretching of aromatic amines, and C–O indicates the vibration of alcohol, ester, and carboxylic acid that facilitated in the green synthesis of AgNPs. The crystalline nature of synthesized AgNPs was confirmed by XRD, while the elemental composition of AgNPs was detected by energy dispersive X-ray analysis (EDX). SEM studies showed the mean particle diameter of silver nanoparticles. The synthesized AgNPs were used for photocatalytic degradation of Orange G and Direct blue-15 (OG and DB-15), which were analyzed by UV-visible spectroscopy. Maximum degradation percentage of OG and DB-15 azo dyes was observed, without any significant silver leaching, thereby signifying notable photocatalytic properties of AgNPs.

The antioxidant and enzyme inhibitory potential of fifteen cycloartane-type triterpenes’ potentials were investigated using different assays. In the phosphomolybdenum method, cycloalpioside D (6) (4.05 mmol TEs/g) showed the highest activity. In 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) cation radical scavenging assays, cycloorbicoside A-7-monoacetate (2) (5.03 mg TE/g) and cycloorbicoside B (10) (10.60 mg TE/g) displayed the highest activities, respectively. Oleanolic acid (14) (51.45 mg TE/g) and 3-О-β-d -xylopyranoside-(23R,24S)-16β,23, 16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 7-monoacetate (4) (13.25 mg TE/g) revealed the highest reducing power in cupric ion-reducing activity (CUPRAC) and ferric-reducing antioxidant power (FRAP) assays, respectively. In metal-chelating activity on ferrous ions, compound 2 displayed the highest activity estimated by 41.00 mg EDTAE/g (EDTA equivalents/g). The tested triterpenes showed promising AChE and BChE inhibitory potential with 3-О-β-d-xylopyranoside-(23R,24S)-16β,23, 16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 2′,3′,4′,7-tetraacetate (3), exhibiting the highest inhibitory activity as estimated from 5.64 and 5.19 mg GALAE/g (galantamine equivalent/g), respectively. Compound 2 displayed the most potent tyrosinase inhibitory activity (113.24 mg KAE/g (mg kojic acid equivalent/g)). Regarding α-amylase and α-glucosidase inhibition, 3-О-β-d-xylopyranoside-(23R,24S)-16β,23, 16α,24-diepoxycycloart-25(26)-en-3β,7β-diol (5) (0.55 mmol ACAE/g) and compound 3 (25.18 mmol ACAE/g) exerted the highest activities, respectively. In silico studies focused on compounds 2, 6, and 7 as inhibitors of tyrosinase revealed that compound 2 displayed a good ranking score (−7.069 kcal/mole) and also that the ΔG free-binding energy was the highest among the three selected compounds. From the ADMET/TOPKAT prediction, it can be concluded that compounds 4 and 5 displayed the best pharmacokinetic and pharmacodynamic behavior, with considerable activity in most of the examined assays.

Multicomponent reactions, especially the Ugi-four component reaction (U-4CR), provide powerful protocols to efficiently access compounds having potent biological and pharmacological effects. Thus, a diverse library of betulinic acid (BA), fusidic acid (FA), cholic acid (CA) conjugates with TEMPO (nitroxide) have been prepared using this approach, which also makes them applicable in electron paramagnetic resonance (EPR) spectroscopy. Moreover, convertible amide modified spin-labelled fusidic acid derivatives were selected for post-Ugi modification utilizing a wide range of reaction conditions which kept the paramagnetic center intact. The nitroxide labelled betulinic acid analogue 6 possesses cytotoxic effects towards two investigated cell lines: prostate cancer PC3 (IC50 7.4 ± 0.7 μM) and colon cancer HT29 (IC50 9.0 ± 0.4 μM). Notably, spin-labelled fusidic acid derivative 8 acts strongly against these two cancer cell lines (PC3: IC50 6.0 ± 1.1 μM; HT29: IC50 7.4 ± 0.6 μM). Additionally, another fusidic acid analogue 9 was also found to be active towards HT29 with IC50 7.0 ± 0.3 μM (CV). Studies on the mode of action revealed that compound 8 increased the level of caspase-3 significantly which clearly indicates induction of apoptosis by activation of the caspase pathway. Furthermore, the exclusive mitochondria targeting of compound 18 was successfully achieved, since mitochondria are the major source of ROS generation.

Diabetes mellitus is a chronic metabolic disorder which is rapidly spreading worldwide. It is characterized by persistent elevated blood glucose level above normal values (hyperglycemia) due to defect in either insulin secretion or in insulin action or both of them. Currently approved oral synthetic antidiabetic drugs such as biguanides, thiazolidinediones, sulfonylureas, and meglitinides have shown undesirable side effects. Therefore, newer approaches and targets for the management of diabetes mellitus are highly desirable. Dipeptidyl peptidase-4 enzyme, α-glucosidase enzyme and sodium-dependent glucose co-transporter 2 (SGLT2) have been recognized as effective therapeutic targets for the management of diabetes mellitus while natural products are alternatives to oral synthetic hypoglycemic agents. During the last two decades, many researchers were working on the identification and the validation of plant-derived products for curing various diseases. Natural products do not only provide useful drugs in their own right but also provide templates for the development of more effective compounds for enhanced therapeutic potential. Herein, we advocated the vital role of natural products as source of new drugs by presenting promising inhibitors of dipeptidyle peptidase-4 enzyme, α-glucosidase enzyme and (SGLT2) obtained from different medicinal plants as potential candidates for drug development against diabetes mellitus. The structure-activity relationship (SAR) of these various inhibitors is also discussed.

Phytochemical investigation of the methanolic extract obtained from the aerial parts of Lagochilus setulosus (Lamiaceae) afforded the new compound 1-methoxy-3-O-β-glucopyranosyl-α-l-oliose (1) together with five known glycosides, namely sitosterol-3-O-β-glucoside (2), stigmasterol-3-O-β-glucoside (3), pinitol (4), 6β-hydroxyl-7-epi-loganin (5), and chlorotuberoside (6). The structures of these compounds were elucidated by extensive spectroscopic analyses, especially HR-MS, 1D and 2D NMR spectroscopy. The in vitro cytotoxic activity of the methanolic extract and the isolated compounds was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and crystal violet (CV) staining assays. In addition, the antifungal activities of the components were evaluated against Botrytis cinerea, Septoria tritici, and Phytophthora infestans. The anthelmintic potential was determined against Caenorhabditis elegans nematodes. Neither the extract nor the isolated compounds showed promising activity in all the bioassays.

Phytochemical investigation of the oleo-gum resins from Boswellia papyrifera afforded one new triterpene, named 3α-hydroxyurs-5:19-diene (1) together with twelve known compounds including eight triterpenoids (2–9), two diterpenoids (10 and 11) and two straight chain alkanes (12 and 13). Similarly ten more known compounds were isolated from the resin of Boswellia sacra including one triterpene (20) and nine boswellic acids (14–19 and 21–23). Herein the compound 2 was first time reporting from natural source along with complete NMR assignment, while compounds 3–11 are known, but reported for the first time from the resin of B. papyrifera. The structure elucidation was done by advance spectroscopic 1D and 2D NMR techniques viz., 1H, 13C, DEPT, HSQC, HMBC, and COSY, and NEOSY, ESI-MS and compared with the reported literature. All compounds were evaluated for their α-glucosidase inhibitory activity and as result eight of them 1, 3, 10, 11, 15, and 17–19 were found significantly active against α-glucosidase with an IC50 value ranging from 15.0 ± 0.84 to 80.3 ± 2.33 µM, while 21 exhibited moderate activity with IC50 of 799.9 ± 4.98 µM. Furthermore, two compounds 24 and 25 were synthesised from 16 and 17 to see the effect of carboxyl group in structural-activity relationship (SAR) study. Compounds 24 and 25 retained good α-glucosidase inhibition as compared to 16 and 17, indicating that carboxylic group play a key role in SAR. In addition, the aforementioned activity of all the active compounds was first time reported for their α-glucosidase inhibition potential. The molecular docking studies showed that all the active compounds well accommodate in the active site of the enzyme. Moreover pharmacokinetic properties of the compounds were predicted in silico, suggesting that the compounds possess drug like properties and excellent ADMET profile.

Phytochemical investigation of Lycium shawii Roem. & Schult provided fourteen compounds, including lyciumate (1), dehydrocostus lactone (2), costunolide (3), catechin(4), lyciumaside (5), emodin (6), emodin-8-O-β- D -glucoside (7), aloe-emodin (8), aloe-emodin-8-O-β- D -glucoside (9), aloe emodin-11- O -rhamnoside (10 ) , chrysophanol - 8 - O -β- D - glucoside (11), nonacosane-10-ol (12), betulinic acid (13) and β -sitosterol glucopyranoside (14). The compounds may be classified as three sesquiterpene lactones (1-3), two phenolic compounds (4 and 5), six anthraquinones (6-11), one long chain alcohol (12), one lupane-type triterpenoid (13) and a steroid (14). Compounds 2, 3, 7 and 9-12 are reported here for the first time as isolated from any species of Lycium as well as from the Solanaceae family while compounds 8, 13 and 14 are reported to be found for the first time in the genus Lycium. All structural assignments were made by comparing the NMR spectral data of the pure isolates with that published in the quoted literature.

In the current investigation, new monomers of myrrhanone B and lupeolic acid were prepared via reaction of triterpenic acids with linkers in the presence of K2CO3. In addition, new bis-myrrhanone B homodimers, myrrhanone B-myrrhanol B heterodimers, and bis-myrrhanone β-boswellic acids heterodimer were prepared. Evaluation of these compounds on the proliferation of four different human cancer cell lines, viz., FaDu (pharynx carcinoma), A2780 (ovarian carcinoma), HT29 (colon adenocarcinoma) and A375 (malignant melanoma) has been performed. It is worth mentioning that compounds 4, 7, 8, 10, and 11 possess potent antiproliferative effect towards HT29 cancer cells with IC50 values of 8.1 μM, 5.4 μM, 8.8 μM, 6.8 μM, and 8.2 μM, respectively. In addition, these compounds display good to moderate antiproliferative activities towards A2780 and A375 with IC50 values ranging from 10.4 to 24.2 μM. Moreover, the molecular docking studies of most active compounds (4, 7, 8, 10 and 11) with six anti-cancer drug targets DHFR, VEGFR2, HER-2/neu, CDK6, hCA-IX and LOX also carried, in order to know the mode of binding interaction and energy of this class of compounds.

Toddalia asiatica (L.) Lam. (Rutaceae) has shown a broad spectrum of biological properties, such as anti-inflammatory, antioxidant, antimicrobial, anti-HIV, and anticancer properties. The present study is concerned with the separation of the main components with broad partition coefficients (KD values) from T. asiatica, using linear gradient high-speed counter-current chromatography (LGCCC) combined with an off-line two-dimensional (2D) mode. Similar to the binary gradient HPLC, the LGCCC mode is operated by the adjustment of the proportion between the mobile phase of 5:5:1:9 (v/v) (pump A) and 5:5:4.5:5.5 (v/v) (pump B) in an n-hexane/ethyl acetate/methanol/water solvent system. The off-line 2D-CCC mode was used in this study for the secondary separation of two similar KD value compounds with n-hexane/ethyl acetate/methanol/water (5:5:4:6, v/v). Notably, six coumarins, namely, tomentin (1), toddalolactone (2), 5,7,8-trimethoxycoumarin (3), mexoticin (4), isopimpinellin (5), and toddanone (6), were efficiently separated. The structures of the pure compounds were elucidated by spectral techniques and compared with the literature.

The chromatographic purification of the n -hexane soluble part of methanolic extract of Seriphidium oliverianum (J. Gay ex Besser) yielded six secondary metabolites that includes two new natural products; diethyl-2,6-diphenyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate ( 1) and 2,6-diacetyl-3,5-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine ( 2 ) along with four known phytochemicals; tetradecyl ferulate ( 3 ), octadecyl coumarate ( 4 ), methyl coumarate ( 5 ) and methyl grevillate ( 6 ). The new compounds were characterized with the help of 1D-, 2D-NMR and high resolution mass spectrometric techniques, whereas, the known compounds were identified through 1D-NMR and mass spectrometry, and in comparison with the literature values. Compound 1 is synthetically known, however, it is first time reported from any natural source, whereas, compound 2 has never been reported from any other source before. All the isolates were screened in anti-urease and anti-glucosidase bioassay but were found inactive.

A series of new 11-keto-β-boswellic acid were partially-synthesized by modifying the hydroxyl and carboxylic acid functional groups of ring A. The structures of the new analogs were confirmed by detailed spectral data analysis. Compounds

Bio-assay guided fractionation of the methanolic extract of Aloe vera resin and Lycium shawii stem successively afforded twenty three compounds; fourteen (1–14) from A. vera and nine (15–23) from L. shawii. All these compounds were characterized by 1D and 2D NMR spectroscopic techniques viz., 1H, 13C, DEPT, HSQC, HMBC, and COSY, and NEOSY, ESI-MS and compared with the reported literature. These compounds were assessed for their potential as urease inhibitors targeted in peptic ulcer. Among crude extracts and fractions of A. vera resin, n-butanol fraction (23.5 ± 1.7 μg·mL−1) showed the most potent urease inhibition followed by methanol (30.9 ± 0.3 μg/mL) and ethyl acetate (31.7 ± 0.5 μg·mL−1). In case of L. shawii, ethyl acetate fraction exhibited the highest urease activity (41.0 ± 1.4 μg/mL) trailed by dichloromethane (55.2 ± 1.5 μg/mL) fraction. Among the isolates, compounds 7, 11 and 23 were found to be excellent urease inhibitors with IC50 values of 14.5 ± 0.90 µM, (16.7 ± 0.16 µM) and 14.0 ± 0.8 µM, respectively. To the best of our knowledge, this is the first report on the urease enzyme inhibitory activity of the said compounds excluding compound 18. In addition, the urease activity of different fractions of L. shawii stem was also reported for the first time. The molecular docking studies showed that all the active compounds well accommodate in the active site of the urease enzyme by interacting with key amino acids.

Acorus tatarinowii Schott is a traditional Chinese medicine used to treat memory and cognitive dysfunction. Because of their efficacy and lower toxic effects, research on α- and β-asarone, the phytoconstituents, has attracted attention owing to their remarkable pharmacological activities. Silver ion coordination complexation high-speed counter-current chromatography was used to separate these isomers from A. tatarinowii extract, coupled with accelerated solvent extraction. Accelerated solvent extraction parameters were investigated with single-factor and orthogonal testing. A two-phase solvent system composed of n-hexane-ethyl acetate-ethanol-water (2:1:2:1, v/v) with 0.50 mol/L silver ions was selected for separation. From 2.0 g crude extract, 1.4 g of β-asarone and 0.09 g of α-asarone were obtained with purities over 98% by sequential sample loading in 20 h. The isolated compounds were identified by electrospray ionization mass spectrometry, 1H and 13C NMR. Silver ions significantly increased the separation factor and retention of the stationary phase. The chromatographic behavior indicated that cis-configuration was more strongly complexed with the silver ion. This was further demonstrated with the help of computational analysis. In conclusion, the established method could be employed to separate other cis-trans or E/Z isomers that form coordination complexes.

Incensole 1 and its acetate 2, found in incense, demonstrate interesting biological activities. Incensole acetate 2 was prepared on a large scale by employing the Paul and Jauch protocol from the crude extracts of Boswellia papyrifera Hochst. 5-epi-Incensole 3, obtained as colorless crystals, was prepared from incensole acetate via three steps; deacetylation, oxidation and reduction. The structure of 5-epi-incensole 3 was elucidated by means of spectroscopic data analysis, and the absolute configuration was established by single crystal X-ray analysis in combination with electronic and vibrational circular dichroism. In particular, the applicability of the solid-state ECD/TDDFT protocol to a compound with only two non-conjugated alkene chromophores was verified.

Two new C-glucosyl chromones named aloeverasides A (1) and B (2) were isolated from the resin of Aloe vera (L.) Burm.f. The structures of the two new natural products were elucidated based on 1D- (1H- and 13C-NMR) and 2D-NMR (COSY, HSQC, and HMBC) spectroscopic techniques and mass spectrometry (ESI-MS). Aloeverasides A (1) and B (2) were evaluated for their anticancer activity, and both induced a 76.4 and 70.5% growth inhibition of the breast cancer cell line (MDA-MB-231) at a concentration of 100 μm. Both compounds were also evaluated for their 1,1-diphenyl-2-picryl-hydrazyl antioxidant, urease enzyme, and α-glucosidase enzyme inhibition activities. Aloeverasides A (1) and B (2) displayed good urease enzyme inhibition activities (62 and 55%, resp.), as well as antioxidant activity in which aloeveraside A (1) had a value of 60% inhibition, while aloeveraside B (2) demonstrated a more potent antioxidant activity with 80% inhibition.

A series of nitrogen heterocycles including the derivatives of 1-deazapurines, were studied for miscellaneous enzyme inhibition activities in search of the potent enzyme inhibitor. The hyperactive enzymes like carbonic anhydrase-II, phosphodiesterase-I, xanthine oxidase, α-glucosidase, and β-glucuronidase were selected for the study. The compounds 1, 2, 3, 6, 8, 11–13 and 15–17, showed significant and selective activities against different enzymes. The compounds 11 and 12 were found the most potent against carbonic anhydrase-II, α-glucosidase and β-glucuronidase in comparison to their standard compounds. These selective inhibitors can be used as lead compounds for development of drugs against various diseases associated with these enzymes.

Two new pregnane glycosides named desmiflavasides C (1) and D (2) were isolated from the sap of Desmidorchis flava (N.E.Br.) Meve & Liede and have had their structures confirmed from 1D and 2D NMR spectroscopic techniques and mass spectrometry (ESIMS). Further, the effects of desmiflavasides C (1) and D (2) on the proliferation of breast and ovarian cancer cells as well as normal breast epithelial cells in culture were examined. Interestingly, desmiflavasides C (1) and D (2) were able to cause a substantial decline in the viability of cancer cells in a concentration-dependent manner. Moreover, treatment of normal cells with compound 2 resulted in no significant growth inhibition, indicating that its cytotoxicity was selective towards cancer cells. Furthermore, the activity of compound 2 against cancer as well as normal epithelial cells was found to be similar to that of a previously reported pregnane glycoside, nizwaside (3). Molecular docking studies of desmiflavasides C (1) and D (2) and nizwaside (3) were carried out to ascertain if it was possible to predict any important binding orientations required of small molecule drug candidates with suggested protein target molecules for the purposes of being able to predict the affinity and activity to an acceptable degree by such compounds. Desmiflavaside D (2) showed a relatively good binding affinity (-22.4449kcal/mol) as compared to the other two compounds viz., nizwaside (3) (-20.0319kcal/mol), and desmiflavaside C (1) (-19.4042kcal/mol). Docking results of the three pregnane glycosides viz., 1-3 revealed that these ligand molecules can accurately interact with the target protein.

Four new pregnane glycosides named desflavasides A-D ( 1–4 ) were isolated from the sap of Desmidorchis flava (N.E.Br) Meve & Liede. The structures of all new compounds were elucidated based on 1D and 2D NMR spectroscopic techniques coupled with mass spectromentry (ESIMS and HRESIMS).

Cichorium intybus L., (chicory) is employed in various traditional medicines to treat a wide range of diseases and disorders. In the current investigation, two new naphthalane derivatives viz., cichorins D (1) and E (2), along with one new anthraquinone cichorin F (3), were isolated from Cichorium intybus. In addition, three previously reported compounds viz., &beta, sitosterol (4), &beta, sitosterol &beta, glucopyranoside (5), and stigmasterol (6) were also isolated from Cichorium intybus. Their structures were established via extensive spectroscopic data, including 1D (1H and 13C) and 2D NMR (COSY, HSQC and HMBC), and ESIMS. Cichorin E (2) has a weak cytotoxic effect on breast cancer cells (MDA-MB-468: IC50: 85.9 &micro, M) and Ewing&rsquo, s sarcoma cells (SK-N-MC: IC50: 71.1 &micro, M), cichorin F (3) also illustrated weak cytotoxic effects on breast cancer cells (MDA-MB-468: IC50: 41.0 &micro, M and MDA-MB-231: IC50: 45.6 &micro, M), and SK-N-MC cells (IC50: 71.9 &micro, M). Moreover compounds 1&ndash, 3 did not show any promising anthelmintic effects.

The distribution and biosynthesis of boswellic acids (BAs) is scarce in current literature. Present study aims to elucidate the BAs biosynthetic and its diversity in the resins of Boswellia sacra and Boswellia papyrifera. Results revealed the isolation of new (3β, 11β-dihydroxy BA) and recently known (as new source, β-boswellic aldehyde) precursors from B. sacra resin along with α-amyrin. Following this, a detailed nomenclature of BAs was elucidated. The quantification and distribution of amyrins (3-epi-α-amyrin, β-amyrin and α-amyrin) and BAs in different Boswellia resins showed highest amyrin and BAs in B. sacra as compared with B. serrata and B. papyrifera. Distribution of BAs significantly varied in the resin of B. sacra collected from dry mountains than coastal trees. In B. sacra, high content of α-amyrin was found in the roots but it lacked β-amyrin and BAs. The leaf part showed traces of β-ABA and AKBA but was deficient in amyrins. This was further confirmed by lack of transcript accumulation of amyrin-related biosynthesis gene in leaf part. In contrast, the stem showed presence of all six BAs which are attributed to existence of resin-secretory canals. In conclusion, the boswellic acids are genus-specific chemical constituents for Boswellia species albeit the variation of the amounts among different Boswellia species and grades.

The Perovskia artemisioides Boiss. essential oil obtained by hydrodistillation method of flowers growing wild in the north of Iran. The study led to the identification of 29 compositions by a combination of HP-5 GC–FID and GC–MS analytical techniques. The constituents were identified in P. artemisioides essential oil with 1,8-cineole (29.9%), camphor (29.5%) and α-pinene (7.8%) as main constituents as well as δ-3-carene (5.1%), camphene (3.3%) and β-pinene (2.7%). The oil was identified by a much larger amount of monoterpenes (87.7%) and sesquiterpenes (6.3%). The results of antimicrobial activity exhibit that the extracted essential oil has presented a high inhibiting activity against five microbial strains up to 18 mm. Also, the MIC and MBC results displayed that Staphylococcus aureus, Escherichia coli and Salmonella typhi were inhibited by P. artemisioides essential oil. Therefore, determination of essential oils in this research showed a relatively similar pattern to those published for the other species of Perovskia.

Royleanumioside (1), a new lupane type triterpenoid, was secluded from the CHCl3 soluble fraction of Teucrium royleanum. The structure of royleanumioside (1) was ascertained by spectral studies including 1D and 2D NMR spectroscopy and by the assessment with the reported data in literature. This new identified compound 1 was further tested for its phytotoxic activity against lettuce seedlings. Interestingly royleanumioside (1) had shown moderate phytotoxic activity.

Phytochemical investigation of the endophytic fungus Microdiplodia sp. afforded a new m-anisaldehyde derivative named microdiplanol (1) and a new 24-methylcholestanol derivative named microdiplane (2). Their structures were confirmed by a comprehensive analysis of 1D and 2D NMR and mass spectrometric data.

The frankincense resin of botanically-certified Boswellia sacra was pyrolyzed and the smoke was trapped into water using self-developed assembly. Two compounds, namely 1,2,4a,9-tetramethyl-1,2,3,4,4a,5, 6,14b-octahydropicene ( 1 ) and 2,9-dimethylpicene ( 2 ) were isolated from n -hexane extract of the smoke-saturated water. Their structures were determined by means of spectroscopic data including ESIMS, 1 H NMR, 13 C NMR, and 2D NMR (COSY, HSQC, HMBC, and NOESY). Dehydration of C-3 alcohols in boswellic acids (BAs) lead to aromatization of ring A followed by dehydrogenation and demethylation to afford triaromatic derivative viz., 1,2,4a,9-tetramethyl-1,2,3,4,4a,5, 6,14b-octahydropicene ( 1 ) and finally penta-aromatic derivative viz., 2,9-dimethylpicene ( 2 ). Compounds 1 and 2 were screened for their antiproliferative effects on MDA-MB-231 breast cancer cells. It was found that these pyrolysate products were capable of inhibiting cancer cell growth. However, this growth inhibitory effect was less when compared to their precursor AKBA (3-acetyl-11-keto-β-boswellic acid). The antiproliferative activity is inversely proportional to loss of functional groups.

The effect of enzyme inhibition, anticancer, antifungal, antioxidants activities of the extracts of Teucrium muscatense obtained with different organic solvents was investigated. Chloroform fraction exhibited promising inhibition (64%) with IC50 value (390 ± 2.0 μg/mL) against urease, while other fractions displayed moderate activity. In case of α-glucosidase and acetyl cholinesterase enzyme inhibition assays, all fractions were found inactive at a concentration of 1.0 mg/mL. The n-hexane fraction of Teucrium muscatense exhibited highest anticancer activity against breast cancer cell (MDAMB231) line at high (100 µg/mL) concentration and also inhibited the growth of F. oxysporum up to 64.3% in case of antifungal activity. EtOAc fraction showed highiest DPPH (70.6%) and ABTS (76.7%) radical scavenging activity at highest concentration (1000 μg/mL). Bioassay guided isolation of EtOAc fraction afforded two flavonoids (1 and 2). Both compounds showed highiest ABTS activity and could be a significant markers in the EtOAc fraction. Anti-lipid peroxidation assay was also performed in which aqueous fraction showed highest percentage of 73.2% at higher concentration (1000 μg/mL) followed by n-BuOH (64.1%) and EtOAc (51.4%) fractions. GC/MS analysis of the essential oil of T. mascatense showed higher percentage of linalool (34.18%), limonene (13.45%), linalyl acetate (10.04%), and β-eudesmol (9.21%). Proximate composition of Teucrium muscatense showed that it contained high amount of ash (19.6%), protein (10.3%), and fiber (17.5%).

Phytochemical investigations of the endophytic fungus of an unidentified Ascomycete, isolated from Meliotus dentatus led to the isolation of two new polyketide metabolites named cis-4-acetoxyoxymellein and 8-deoxy-6-hydroxy-cis-4-acetoxyoxymellein. The structures of the two new polyketides were confirmed on the basis of 1D and 2D NMR techniques. Preliminary studies showed that both of the new polyketides displayed strong antibacterial activity towards Escherichia coli and Bacillus megaterium. cis-4-Acetoxyoxymellein and 8-deoxy-6-hydroxy-cis-4-acetoxyoxymellein also displayed good antifungal and algicidal activities toward Microbotryum violaceum, Botrytis cinerea, and Septoria tritici.

Heterocyclic compounds (HCs) have drawn the utmostattention of researchers due to their extensive practicalapplications. HCs act as lead structures for the designingof new drugs [1]. Synthetic heterocycles are widely usedas fungicides, herbicides, anticorrosive agents and flavor-ing agents [2,3]. The heterocycles are present in all typesof organic compounds and find use in electronics, phar-macology and material science. Among the heterocycles,sulfur and nitrogen containing compounds are bestowedwith broad range applications [4].Heterocycles are used in the form of essential aminoacids, proline, histidine and tryptophan [5]. Such com-pounds are also used as photosynthetic pigment chloro-phyll and in the form of hormones kinetin, heteroauxinand cytotoxin [6]. HCs are widely used in natural drugsi.e. quinine, theophylline, theobromine, emetine, atropine,and morphine [7–10]. From agricultural point of view ni-trogenous heterocyclic compounds have potential applica-tions in the manufacturing of pesticides, agrochemicalsand disinfectants [11].In addition to useful applications discussed above,many of nitrogen containing heterocyclic compoundshave also been reported to be carcinogenic or increasethe carcinogenic activity [12]. Among the HCs, quinoxa-lines are especially used for the synthesis of significantlyimportant biologically active compounds such as pyrazineand merfazin amides. Actinomycin, lomacine and actino-lite are known to exert their antibiotic action due to thepresence of quinoxaline ring in their structures [13].Some quinoxaline based compounds are bestowed withdental applications [13].Moreover, quinoxalines with high electron donor prop-erties are reported to have broad range applications inpolymer chemistry [14]. Fluorine substituted quinoxalineshave been documented to enhance the photovoltaic prop-erties of polymer based solar cells by a mechanism in-volving intramolecular charge transfer from electron-richunit to the electron withdrawing unit [15]. Quinoxalinederivatives are also used as dyes because of their highfluorescence and low redox potentials. In general, thehigher the oxidation potential of the dye, the lower thevalue of quenching constant and vice versa [16]. Becauseof the presence of electron deficient N-heterocycles, qui-noxalines can effectively tune the band gap and energylevels, thus, exhibiting promising applications in photovol-taic cells [17]. The robust electrochemical and opticalproperties of quinoxaline derivatives have spurred onmany researchers to apply these compounds as photo-sen-sitizers.Abstract: The electrochemical behavior of a biologicallyimportant heterocyclic compound, 1,3-dioxolo[4,5-g]pyrido[2,3-b]quinoxaline was investigated by cyclic,square wave and differential pulse voltammetry in solu-tions of different pH. Kinetic and thermodynamic param-eters like standard rate constant, diffusion coefficient, ap-parent energy of activation

Two new cryptosporioptide-derived polyketides cryptosporioptides A (2) and B (3) were isolated from the extract of endophytic fungus Cryptosporiopsis sp. associated with the shrub, Viburnum tinus. The structures of the isolates were determined through spectral analysis including 1D NMR ((1)H, (13)C) and 2D NMR (HSQC, HMBC, COSY) techniques, HR-FAB-MS and by comparison with the reported data of cryptosporioptide (1). The relative stereochemistry was assigned with the help of NOESY analysis, the molecular model, and comparison of the optical rotation values with the reference compound 1.

Phytochemical investigation of the endophytic fungus Coniothyrium sp. resulted in the isolation of a new phenoxyphenyl ether, named coniothyren (1), and two known compounds, coniol (2) and (+)-epoxydon (3). The structure of the new compound was elucidated by detailed spectroscopic analysis, namely, (1)H NMR, (13)C NMR, COSY, HMQC, HMBC, and HR-EI-MS. Preliminary studies demonstrated that (+)-epoxydon (3) displayed good antibacterial and antialgal activities toward Bacillus megaterium and Chlorella fusca, respectively.

The synthetic uses of different peroxides for organic synthesis have been widely studied. Among these peroxides, meta-chloroperbenzoic acid (mCPBA) is an efficient oxidizing reagent and have been used for many oxidative transformations. mCPBA is widely used for chemical transformations such as the oxidation of carbonyl compounds, iminoindolines, olefins, imines, alkanes, silyl enol ethers, N- and S-heterocycles, active methylene groups, fluoromethylated allylic bromides, cyclic acetals, N-substituted phthalimidines, selenides, furans and phosphates. The purpose of this review is to collect and discuss the synthetic applications of meta-chloroperbenzoic acid (mCPBA) over the past few decades.

Four known hydroxyanthraquinones (1-4) together with four new derivatives having a tetralone moiety, namely coniothyrinones A-D (5-8), were isolated from the culture of Coniothyrium sp., an endophytic fungus isolated from Salsola oppostifolia from Gomera in the Canary Islands. The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configurations of coniothyrinones A (5), B (6), and D (8) were determined by TDDFT calculations of CD spectra, allowing the determination of the absolute configuration of coniothyrinone C (7) as well. Coniothyrinones A (5), B (6), and D (8) could be used as ECD reference compounds in the determination of absolute configuration for related tetralone derivatives. This is the first report of anthraquinones and derivatives from an isolate of the genus Coniothyrium sp. These compounds showed inhibitory effects against the fungus Microbotryum violaceum, the alga Chlorella fusca, and the bacteria Escherichia coli and Bacillus megaterium.