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.

Medicinal plants used in the treatment of tuberculosis - Ethnobotanical and ethnopharmacological approaches.

Tuberculosis is a highly infectious disease declared a global health emergency by the World Health Organization, with approximately one third of the world's population being latently infected with Mycobacterium tuberculosis. Tuberculosis treatment consists in an intensive phase and a continuation phase. Unfortunately, the appearance of multi drug-resistant tuberculosis, mainly due to low adherence to prescribed therapies or inefficient healthcare structures, requires at least 20 months of treatment with second-line, more toxic and less efficient drugs, i.e., capreomycin, kanamycin, amikacin and fluoroquinolones. Therefore, there exists an urgent need for discovery and development of new drugs to reduce the global burden of this disease, including the multi-drug-resistant tuberculosis. To this end, many plant species, as well as marine organisms and fungi have been and continue to be used in various traditional healing systems around the world to treat tuberculosis, thus representing a nearly unlimited source of active ingredients. Besides their antimycobacterial activity, natural products can be useful in adjuvant therapy to improve the efficacy of conventional antimycobacterial therapies, to decrease their adverse effects and to reverse mycobacterial multi-drug resistance due to the genetic plasticity and environmental adaptability of Mycobacterium. However, even if some natural products have still been investigated in preclinical and clinical studies, the validation of their efficacy and safety as antituberculosis agents is far from being reached, and, therefore, according to an evidence-based approach, more high-level randomized clinical trials are urgently needed.

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.

Antidiabetic Potential of Medicinal Plants and Their Active Components.

Diabetes mellitus is one of the major health problems in the world, the incidence and associated mortality are increasing. Inadequate regulation of the blood sugar imposes serious consequences for health. Conventional antidiabetic drugs are effective, however, also with unavoidable side effects. On the other hand, medicinal plants may act as an alternative source of antidiabetic agents. Examples of medicinal plants with antidiabetic potential are described, with focuses on preclinical and clinical studies. The beneficial potential of each plant matrix is given by the combined and concerted action of their profile of biologically active compounds.

Athyrium plants - Review on phytopharmacy properties.

Athyrium plants consist of more than 230 species that are largely distributed in the Sino-Himalayan region and the Western Pacific islands. Athyrium species are being used in traditional medicine worldwide to treat various ailments such as cough, rheumatic pain, scorpion stings, sores, burns and scalds, intestinal fever, pain, specifically breast pain during child birth, to increase milk flow, as an antiparasitic, anthelmintic, and carminative. A deep look in the literature has revealed that Athyrium species have been poorly investigated for their food preservative applications and in vivo and in vitro biological and phytochemical studies. However, some Athyrium species have demonstrated antimicrobial, anti-inflammatory, antioxidant, antiproliferative and anti-HIV potential. Athyrium multidentatum (Doll.) Ching is the most investigated species and the biological activities of their extracts, such as they antioxidant properties, seem to be related to the sulfate contents of their polysaccharides. This review provides an update on the ethnopharmacology, phytochemistry and biological properties of Athyrium plants that might be useful for further research. Of course, well-designed clinical trials will be required for some species to be used as therapy.

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.

Interleukin (IL)-8 polymorphisms contribute in suicide behavior.

Previous studies have highlighted the role of immune dysregulation in suicide behavior. Interleukin (IL)-8 is a chemokine with neuroprotective effects whose lower serum concentrations have been detected in individuals committed suicide. In the present study, we genotyped three single nucleotide polymorphisms (SNPs) within IL-8 gene (rs4073, rs2227306 and rs1126647) in 229 individuals who attempted suicide with soft suicide methods, 235 suicide victims and 290 individuals without any history of psychiatric disorders or suicide attempt. The T allele of rs4073 was significantly over-represented in suicide attempt group compared with both control and completed suicide groups (adjusted P values of 8.3E-7 and 9.8E-8 respectively). This SNP was associated with suicide attempt in both dominant and co-dominant models (P values of 6.2E-9 and 4.3 E-8 respectively). The genotype and allele frequencies of other SNPs were not significantly different among the three study groups. The T C A haplotype (rs4073, rs2227306 and rs1126647 respectively) were significantly less prevalent in completed suicide group compared with suicide attempt group (OR (95% CI) = 0.63 (0.46-0.86), adjusted P value = 0.03). Besides, the A T A haplotype has significant lower frequency in individuals who attempted soft suicide compared with controls (OR (95% CI) = 0.44 (0.26-0.75), adjusted P value = 0.02). However, this haplotype was significantly more prevalent in individuals attempted hard methods compared with those attempted soft methods (OR (95% CI) = 2.21 (1.26-3.87), adjusted P value = 0.04). The present study provided further evidence for the role of IL-8 in suicide behavior.

Antibacterial activity of some Lamiaceae species against Staphylococcus aureus in yoghurt-based drink (Doogh).

Doogh is a dairy drinkable fermented product, whose shelf-life and quality is mostly affected by bacteria such as Staphylococcus spp.. This study investigated the antibacterial activity of essential oils (EOs) from Thymus vulgaris L., Mentha piperita L. and Ziziphora tenuior L., alone or in combination, against Staphylococcus aureus in industrial doogh. A three-level and three-variable face centered central composite design experiment was used. Results showed that EOs significantly inhibited S. aureus growth after 1 and 7 days of storage. According to the model, the maximum inhibition was obtained in the presence of 0.2% of EO, independently of the type, and no synergistic or additive effects were observed. Slightly lower S. aureus survivals were observed at the maximum concentration of Z. tenuior EO. In spite of the antimicrobial activity of these EOs, further research is needed to assess their performance in food matrix and, in particular, in dairy product.

Medicinal Plants Used in the Treatment of Human Immunodeficiency Virus.

Since the beginning of the epidemic, human immunodeficiency virus (HIV) has infected around 70 million people worldwide, most of whom reside is sub-Saharan Africa. There have been very promising developments in the treatment of HIV with anti-retroviral drug cocktails. However, drug resistance to anti-HIV drugs is emerging, and many people infected with HIV have adverse reactions or do not have ready access to currently available HIV chemotherapies. Thus, there is a need to discover new anti-HIV agents to supplement our current arsenal of anti-HIV drugs and to provide therapeutic options for populations with limited resources or access to currently efficacious chemotherapies. Plant-derived natural products continue to serve as a reservoir for the discovery of new medicines, including anti-HIV agents. This review presents a survey of plants that have shown anti-HIV activity, both in vitro and in vivo.

Development and Validation of a GC/MS Method for Simultaneous Determination of 7 Monoterpens in Two Commercial Pharmaceutical Dosage Forms.

Terpenes are active constituents of many pharmaceutical dosage forms with natural products origin. One of the challenges in developing dosage forms with herbal origin is their standardization as pharmaceutical products. GC-Mass is the most decisive and reliable technique to fulfill the requirements in this regard. In the present study, a reliable, rapid, and accurate method was developed for determination of 7 monoterpenoids in two selected pharmaceutical dosage forms (rowatinex and rowachol soft gelatin capsules) by gas chromatography-mass spectrometry triple quadrupole selected ion monitoring GC/MS-TQ-SIM. The method was validated for various parameters such as precision, linearity, accuracy, solution stability, limit of detection, and quantification. The average recovery of terpens was in the range of 91.6-105.7%. The method was proved to be repeatable with RSD in the range of 0.28-11.18 for all of the concentration levels. The developed method is simple, rapid, and sensitive and was applied for determination of alpha pinene, camphene, beta pinene, cineol, fenchone, borneol, trans-anethol and menthol in a few batches of rowachol and rowatinex capsules purchased from local drug stores.

RETRACTED: Medicinal plants used in the treatment of tuberculosis - Ethnobotanical and ethnopharmacological approaches.

Tuberculosis is a highly infectious disease declared a global health emergency by the World Health Organization, with approximately one third of the world's population being latently infected with Mycobacterium tuberculosis. Tuberculosis treatment consists in an intensive phase and a continuation phase. Unfortunately, the appearance of multi drug-resistant tuberculosis, mainly due to low adherence to prescribed therapies or inefficient healthcare structures, requires at least 20months of treatment with second-line, more toxic and less efficient drugs, i.e., capreomycin, kanamycin, amikacin and fluoroquinolones. Therefore, there exists an urgent need for discovery and development of new drugs to reduce the global burden of this disease, including the multi-drug-resistant tuberculosis. To this end, many plant species, as well as marine organisms and fungi have been and continue to be used in various traditional healing systems around the world to treat tuberculosis, thus representing a nearly unlimited source of active ingredients. Besides their antimycobacterial activity, natural products can be useful in adjuvant therapy to improve the efficacy of conventional antimycobacterial therapies, to decrease their adverse effects and to reverse mycobacterial multi-drug resistance due to the genetic plasticity and environmental adaptability of Mycobacterium. However, even if some natural products have still been investigated in preclinical and clinical studies, the validation of their efficacy and safety as antituberculosis agents is far from being reached, and, therefore, according to an evidence-based approach, more high-level randomized clinical trials are urgently needed.

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].

Antimicrobial Compounds from Drypetes staudtii.

Antimicrobial-directed phytochemical investigation of the MeOH extract of Drypetes staudtii afforded two new compounds, 4,5-(methylenedioxy)-o-coumaroylputrescine (1), 4,5-(methylenedioxy)-o-coumaroyl-4'-N-methylputrescine (2), along with seven known natural products 4α-hydroxyeremophila-1,9-diene-3,8-dione (3), drypemolundein B (4), friedelan-3ß-ol (5), erythrodiol (6), ursolic acid (7), p-coumaric acid (8), and ß-sitosterol (9). Structures of compounds 1 - 9 were elucidated with the aid of extensive NMR and mass spectral studies. All of the isolates exhibited antibacterial activity against Gram-positive and Gram-negative bacteria with minimum inhibitory concentration (MIC) in the range of 8 - 128 µg/ml. Compounds 1 - 2 were also moderately active against Candida albicans with an MIC value of 32 µg/ml.

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.

Bioactive steroidal alkaloids from Buxus macowanii Oliv.

Chemical investigation of the crude methanolic extract of Buxus macowanii resulted in the isolation of five new steroidal alkaloids, 31-hydroxybuxatrienone (1), macowanioxazine (2), 16α-hydroxymacowanitriene (3), macowanitriene (4), macowamine (5), along with five known steroidal bases, Nb-demethylpapillotrienine (6), moenjodaramine (7), irehine (8), buxbodine B (9) and buxmicrophylline C (10). Structures of compounds 1-10 were elucidated with the aid of spectroscopic methods including 1D and 2D NMR techniques and mass spectrometry. Compounds 1, 3, and 4 belong to a rare class of Buxus alkaloids having Δ(1,2) 9(10→19) abeo triene system. All isolates were evaluated for in vitro acetylcholinesterase (AChE) inhibitory activity and found to exhibit moderate to weak anti-AChE activity with IC50 values in the range of 10.8-98µM. Compounds 1 and 6 were also moderately active in BACE1 inhibitory assay.