Synthesis, characterization, in-silico, and pharmacological evaluation of new 2-amino-6­trifluoromethoxy benzothiazole derivatives.

Alzheimer's disease (AD), a relentless neurodegenerative disorder, is still waiting for safer profile drugs, risk factors affecting AD's pathogenesis include aß accumulation, tau protein hyperphosphorylation, and neuroinflammation. This research aimed to synthesize 2-amino-6­trifluoromethoxy benzothiazole schiff bases. Synthesis was straightforward, combining the riluzole skeleton with compounds containing the azomethine group. Schiff bases synthesized were characterized spectroscopically using proton NMR (1H NMR), and FTIR. In-vivo biological evaluation against scopolamine-induced neuronal damage revealed that these newly synthesized schiff bases were effective in protecting neurons against neuroinflammatory mediators. In-vitro results revealed that these compounds had remarkable potential in improving the anti-oxidant levels. It downregulated glutathione (GSH), glutathione S-transferase (GST), catalase levels, and upregulated lipid peroxidation (LPO) levels. Immunohistochemical studies revealed that groups treated with the newly synthesized schiff bases had reduced expression of inflammatory mediators such as cyclooxygenase 2 (COX-2), JNK, tumor necrosis factor (TNF-α), nuclear factor kappa B (NF-kB) in contrast to the disease group. Moreover, molecular docking studies on these compounds also showed that they possessed a better binding affinity for above mentioned inflammatory mediators. The results of these studies showed that 2-amino-6-trifluoromethoxy benzothiazole schiff bases are remarkably effective against oxidative stress-mediated neuroinflammation.

New pyrazolone derivatives, synthesis, characterization, and neuroprotective effect against PTZ- induced neuroinflammation in mice.

Objectives: The study was aimed at synthesis of the new derivatives of the pyrazolone nucleus, and their spectroscopic and pharmacological analysis and evaluation. Materials and Methods: Three series of compounds, with 2-picolinic acid (I a-d), 3-picolinic acid (II a-d), and 4-picolinic acid (III a-d) were synthesized and characterized by FT-IR, 1HNMR, 13C NMR, elemental, and melting points. The new compounds were then evaluated for their anti-oxidant, anti-inflammatory, and anti-epileptic potential. The hind paw edema model was used to screen anti-inflammatory potential, while the anticonvulsant effect was evaluated by employing the acute model of anti-epileptic activity. The in vivo anti-oxidant potential was determined through glutathione (GSH), glutathione-S-transferase (GST), catalase, and lipid peroxidase enzyme (LPO) assays. The expression of key biomarkers involved in inflammation and neuroprotection, including tumor necrotic factors alpha (TNF-α) and phosphorylated nuclear factor kappa B (NF-κB), was detected through enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Results: The tested compounds showed anti-oxidant potential. The selected compounds exhibited good anti-inflammatory potential. The PTZ-induced elevation of these inflammatory mediators and oxidative stress were ameliorated significantly by the selected compound Ic. Results of molecular analysis (ELISA and Western blot analysis) for potent compound Ic showed a prominent inhibitory effect against neuroinflammatory mediators, including TNF-α and NF-κB. Conclusion: It is concluded that the derivative Ic ameliorated PTZ-induced seizures, oxidative stress, and inflammatory cascades by regulating the NF-κB/ TNF-α/ROS pathway.

Cytotoxic and antimicrobial activities of two new sesquiterpenoids from red sea brittle star Ophiocoma dentata.

Bioactive compounds were extracted from a locally available brittle star; Ophiocoma dentata, collected from the Red Sea, Egypt. Two new sesquiterpenoids; 8, 11-epoxy-9(15)-himachaladiene-4-ol (O8-ophiocomane) and, 11-epoxy-9(15)-himachaladiene-4-ol (O7-ophiocomane) were isolated and characterized using appropriate techniques. Structure elucidation was estimated via 1D NMR, 2D NMR, FT-IR and mass spectroscopy analyses. The isolated compounds were tested for cytotoxic, antibacterial and antifungal activities. Pure compounds showed a dose dependent reduction in MCF-7 cells viability with LC50 of 103.5 and 59.5 µg/ml for compounds 1 and 2 respectively compared to the chemotherapeutic drug cisplatin (47.4 µg/ml). In vivo experiments showed that O. dentate extract significantly reduced tumor progression and improved hematological parameters and liver functions of tumor-bearing mice when administered either before or after tumor cells' injection. The most remarkable antimicrobial effects of O. dentate crude extract were against Staphylococcus aureus, Vibrio damsela and Pseudomonas aeruginosa while the pure compounds showed activity against P. aeruginosa alone. Neither the crude extract nor the pure compounds have shown activity against Aeromonas hydrophila. These results indicates that O. dentata extract and newly isolated compounds have shown a promising cytotoxic, antiproliferative and antimicrobial activities that might be useful for pharmaceutical applications.

First report of steroid derivatives isolated from starfish Acanthaster planci with anti-bacterial, anti-cancer and anti-diabetic activities.

Chemical studies on Acanthaster planci have afforded two steroids, 5α-cholesta-24-en-3ß,20ß-diol-23-one (1) and 5α-cholesta-9(11)-en-3ß, 20ß-diol (2). Structures compounds 1 and 2 were determined with the help of spectroscopic studies. Compound 1 showed strong antibacterial activity (21.0 ± 0.06 mm) against P. aeruginosa. Compounds 1 and 2 were also active against human breast carcinoma cells (MCF-7) with LC50 values of 49 ± 1.6 and 57.5 ± 1.5 µg/ml, respectively. This bioactivity was comparable to the currently used anticancer agent, cisplatin (LC50 46 ± 1.1 µg/ml). Compounds 1 and 2 exhibited anti-α-glucosidase activity with IC50 values of 58 ± 0.8 and 55 ± 0.5 µg/ml, respectively, whereas IC50 of Acarbose as a positive control was found to be 36 ± 0.4 µg/ml in our bioassay.

Prosopis Plant Chemical Composition and Pharmacological Attributes: Targeting Clinical Studies from Preclinical Evidence.

Members of the Prosopis genus are native to America, Africa and Asia, and have long been used in traditional medicine. The Prosopis species most commonly used for medicinal purposes are P. africana, P. alba, P. cineraria, P. farcta, P. glandulosa, P. juliflora, P. nigra, P. ruscifolia and P. spicigera, which are highly effective in asthma, birth/postpartum pains, callouses, conjunctivitis, diabetes, diarrhea, expectorant, fever, flu, lactation, liver infection, malaria, otitis, pains, pediculosis, rheumatism, scabies, skin inflammations, spasm, stomach ache, bladder and pancreas stone removal. Flour, syrup, and beverages from Prosopis pods have also been potentially used for foods and food supplement formulation in many regions of the world. In addition, various in vitro and in vivo studies have revealed interesting antiplasmodial, antipyretic, anti-inflammatory, antimicrobial, anticancer, antidiabetic and wound healing effects. The phytochemical composition of Prosopis plants, namely their content of C-glycosyl flavones (such as schaftoside, isoschaftoside, vicenin II, vitexin and isovitexin) has been increasingly correlated with the observed biological effects. Thus, given the literature reports, Prosopis plants have positive impact on the human diet and general health. In this sense, the present review provides an in-depth overview of the literature data regarding Prosopis plants' chemical composition, pharmacological and food applications, covering from pre-clinical data to upcoming clinical studies.

Triterpenoid corosolic acid attenuates HIF-1 stabilization upon cobalt (II) chloride-induced hypoxia in A549 human lung epithelial cancer cells.

Hypoxia-inducible factor-1 is a target for the management of cancer. Here, the anti-proliferation properties of corosolic acid (CA) against A549 human lung epithelial cancer cells in CoCl2-induced hypoxia is reported. CA was isolated from the roots of Salvia syriaca based on a bioassay-guided isolation platform and identified by 1D and 2D NMR experiments. Several cytotoxicies and genotoxicity analyses were performed using MTT, DAPI, cell cycle, DNA ladder, and annexin V/PI detection. Cobalt chloride (CoCl2) was used to stimulate hypoxia. The adaptation of A549 cells to a stimulated hypoxic condition in the presence of CA was evaluated. CA decreased the growth of A549 cells with an IC50 of 12 µg/mL at 48 h. Also, chromatin condensation and DNA fragmentation were detected as signs of apoptosis occurrence. CA induced ~85% apoptosis and even 1% necrosis. The expression of hypoxia-inducible factor-1 α (HIF-1α), HIF-1ß and downstream genes was strongly suppressed in the presence of CA in CoCl2-stimulated hypoxia condition. Results indicated that CA has remarkable cytotoxicity against the cancerous cell in hypoxia condition and may be regarded for preparation of new formulations for possible uses as supplement and medicine in cancer therapy.

Design, Synthesis and Evaluation of Substituted Aryl-2-Nitrovinyl Derivatives as Small Molecules Proteasome Inhibitors.

Based on the existing structure activity relationship for proteasome inhibitors, a number of substituted aryl-2-nitrovinyl derivatives have been synthesized as Michael acceptor and their cytotoxicity and proteasome inhibitory effects were evaluated on two cancer cell lines. Compound 2d exhibited IC50 values of 0.71 and 17.79 µM comparable to bortezomib against MCF-7 and PC-3, respectively. The results show that the electronic properties and steric hindrance can affect the interaction of these small molecules with their receptor at the active site of the enzyme while the presence of CH2OH group on α-carbon of Michael acceptor is favorable, and para substitution of OMe on phenyl ring of ß-carbon can increase the inhibitory potencies. Molecular docking studies confirm our experimental findings about mode of binding of our compounds with 20S proteasome.

Biologically active perspective synthesis of heteroannulated 8-nitroquinolines with green chemistry approach.

A new class of pyrazolo[4,3-c]quinoline (5a-i, 7a-b) and pyrano[3,2-c]quinoline (9a-i) derivatives were designed and synthesized in moderate to good yields by microwave conditions. To enhance the yield of pyrano[3,2-c]quinoline derivatives, multicomponent one-pot synthesis has been developed. The synthesized compounds were identified by spectral and elemental analyses. Compounds 9a and 9i showed good antibacterial activity against Gram-positive and Gram-negative bacterial strains. All of the new compounds exhibited weak to moderate antioxidant activity, compound 9d exerted significant antioxidant power. The cytotoxicity of these compounds were also evaluated against MCF-7 (breast) and A549 (Lung) cancer cell lines. Most of the compounds displayed moderate to good cytotoxic activity against these cell lines. Compound 9i was found to be significantly active in this assay and also induced cell death by apoptosis. Molecular docking studies were carried out using EGFR inhibitor in order to determine the molecular interactions.

Synthesis of first ever 4-quinolone-3-carboxylic acid-appended spirooxindole-pyrrolidine derivatives and their biological applications.

A series of 4-quinolone-3-carboxylic acid-containing spirooxindole-pyrrolidine derivatives was synthesized via multicomponent 1,3-dipolar cycloaddition reactions of azomethine ylides with new (E)-4-oxo-6-(3-phenyl-acryloyl)-1,4-dihydroquinoline-3-carboxylic acids in good yields with high regioselectivity. The cycloadducts were characterized by analytical and spectral data including [Formula: see text], [Formula: see text], 2D NMR and mass spectroscopy. The structure of one of the compounds (8a) was investigated theoretically by computational techniques. DFT studies support the proposed mechanism for this cycloaddition reaction. Furthermore, antibacterial activities of the new compounds were evaluated against Gram-positive and Gram-negative bacterial strains. Compounds 8f, 8m and 8p showed potent inhibition activities against selected bacteria. The in vitro cytotoxicity of spirooxindole derivatives (8a-r) was evaluated against MCF-7 breast cancer cell line. Among the various compounds tested, compound 8f [Formula: see text] showed significant cytotoxic activity compared to the standard drug doxorubicin [Formula: see text].

A new DNA-intercalative cytotoxic allylic xanthone from Swertia corymbosa.

Phytochemical investigation of the CHCl3 fraction of Swertia corymbosa resulted in the isolation of a new 3-allyl-2,8-dihydroxy-1,6-dimethoxy-9H-xanthen-9-one (1), along with four known xanthones, gentiacaulein (3), norswertianin (4), 1,3,6,8-tetrahydroxyxanthone (5), and 1,3-dihydroxyxanthone (6). Structure of compound 1 was elucidated with the aid of IR, UV, NMR, and MS data, and chemical transformation via new allyloxy xanthone derivative (2). Compounds 1-6 exhibited various levels of antioxidant and anti-α-glucosidase activities. Absorption and fluorescence spectroscopic studies on 1-6 indicated that these compounds could interact with calf thymus DNA (CT-DNA) through intercalation and with bovine serum albumin (BSA) in a static quenching process. Compound 1 was found to be significantly cytotoxic against human cancer cell lines HeLa, HCT116, and AGS, and weakly active against normal NIH 3T3 cell line.

Axially chiral biscarbazoles and biological evaluation of the constituents from Murraya koenigii.

Chemical investigation of the fruit pulp of Murraya koenigii resulted in the identification of two new dimeric carbazole alkaloids, bisgerayafoline D (1) and bismahanimbinol (2) along with four known alkaloids, bispyrayafoline (3), O-methyl mahanine (4), O-methyl mukonal (5), and mahanine (6). Structures of 1-6 were determined with the aid of UV, IR, Mass and extensive NMR spectroscopic studies. Absolute configurations of biaryls in 1 and 2 were assigned using a combination of computational Circular Dichroism (CD) and experimental electronic CD spectroscopic data. Compounds 1-6 were evaluated for anti-oxidant, anti-α-glucosidase, DNA binding, protein interactions and cytotoxic activities. Among all the isolates, mahanine (6) was found to exhibit significant radical scavenging and α-glucosidase inhibitory activities. Compound 6 was also found to be active in cytotoxicity assay against three human cancer cell lines HeLa, HCT116, AGS and this compound was weakly active against normal mouse embryonic fibroblasts (NIH3T3).

Bioactive dimeric carbazole alkaloids from Murraya koenigii.

Phytochemical studies on the CHCl3 extract of the fruit pulp of Murraya koenigii afforded three new dimeric carbazole alkaloids, bisgerayafolines A-C (1-3). Bisgerayafolines A-C (1-3) are structurally unique dimeric carbazole alkaloids comprising geranyl moieties incorporated in their structures. Compounds 1-3 exhibited various levels of antioxidant, anti-α-glucosidase, DNA binding, and cytotoxic activities and protein interactions.

Glutathione S-transferase inhibiting chemical constituents of Caesalpinia bonduc.

Glutathione S-transferase inhibition assay-guided fractionations on the ethanolic extract of the bark of Caesalpinia bonduc resulted in the isolation of a new sterol, 17-hydroxy-campesta-4,6-dien-3-one (1) along with four known compounds, 13,14-seco-stigmasta-5,14-dien-3alpha-ol (2), 13,14-seco-stigmasta-9(11),14-dien-3alpha-ol (3), caesaldekarin J (4) and pipataline (5) as active constituents. Structures of compounds 1-5 were established on the basis of extensive NMR spectroscopic studies. The compounds (1-5) were isolated on the basis of their inhibitory activity against glutathione S-transferase, an enzyme that has been implicated in resistances during treatment of cancer and parasitic infections. Efforts to study structure-activity relationships of compounds 2 and 3 were also made by modifying their structures. The IC50 values of these compounds and their derivatives ranged from 57-380 microM and were compared to the inhibitory effects due to sodium taurocholate, an isoprene-derived GST inhibitor (IC50=398 microM). A plausible biosynthesis of 13,14-seco-steroids has also been proposed.