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Abstract The Astragalus grahamianus (AG) Royle ex. Benth is traditionally used for the treatment of various human disorders. The current research work is aimed to explore the neuroprotective anti-Parkinson effects of various fractions of Astragalus grahamianus (A. grahamianus). Fine powder of Astragalus grahamianus was extracted with 70% methanol and then fractionated with various solvents on the basis of polarity. Standard protocols were used to investigate the bioactive constituents present in the various plant fractions. In-vitro antioxidant potential of various fractions was checked using diverse free radicals. In-vivo rats model was used to determined the neuroprotective effects of methanol fraction of A. grahamianus. The results revealed that various fractions of A. grahamianus contain flavonoids, cardiac glycosides, steroids, gums, terpenes, proteins, and carbohydrates except chloroform fraction lake the presence of steroids, cardiac glycosides, gums and saponins, aqueous fraction of steroids, terpenoids, gums and saponins, n-Hexane fraction steroids, carbohydrates, alkaloids, gums and flavonoids. The highest amount of total phenolic contents was found in AGME (32.67 ± 2.3 mg GAE / g). The AGME also showed enhanced free radicals cations potential against DPPH, ABTS and H2O2, respectively. The correlation between AOA (antioxidant activity) and TPC (total phenolic contents) revealed to be substantial. Relative R2 values for ABTS, H2O2, and DPPH activity are 0.9974, 0.9845, and 0.9678, respectively. The in-vivo neuroprotective activities showed significant results. Our findings highlight significant antioxidant, and neuroprotective possessions of AGME attributed to powerful bioactive compounds.

Abstract Aim of the study Cardiovascular disease (CVD) seriously endangers human health and is characterized by high mortality and disability. The effectiveness of Dracocephalum moldavica L. in the treatment of CVD has been proven by clinical practice. However, the mechanism by which DML can treat CVD has not been systematically determined. Materials and methods The active compounds in DML were screened by literature mining and pharmacokinetic analysis. Cytoscape software was used to construct the target-disease interaction network of DML in the treatment of CVD. Gene ontology and signalling pathway enrichment analyses were performed. The key target pathway network of DML compounds was constructed and verified by pharmacological experiments in vitro. A hydrogen glucose deprivation/reoxygenation model was established in H9c2 cells using hypoxia and glucose deprivation for 9 h combined with reoxygenation for 2 h. The model simulated myocardial ischaemic reperfusion injury to investigate the effects of total flavonoids of Cymbidium on cell viability, myocardial injury markers, oxidative stress levels, and reactive oxygen radical levels. Western blot analysis was used to examine NOX-4, Bcl-2/Bax, and PGC-1α protein expression. Results Twenty-seven active components were screened, and 59 potential drug targets for the treatment of CVD were obtained. Through the compound-target interaction network and the target-disease interaction network, the key targets and key signalling pathways, such as NOX-4, Bcl-2/Bax and PGC-1α, were obtained. TFDM significantly decreased LDH and MDA levels and the production of ROS and increased SOD activity levels in the context of OGD/R injury. Further studies indicated that NOX-4 and Bax protein levels and the p-P38 MAPK/P38 MAPK andp-Erk1/2/Erk1/2 ratios were suppressed by TFDM. The protein expression of Bcl-2 and PGC-1α was increased by TFDM. Conclusions Our results showed that DML had multicomponent, multitarget and multichannel characteristics in the treatment of CVD. The mechanism may be associated with the following signalling pathways: 1) the NOX-4/ROS/p38 MAPK signalling pathway, which inhibits inflammation and reactive oxygen species (ROS) production, and 2) the Bcl-2/Bax and AMPK/SIRT1/PGC-1α signalling pathways, which inhibit apoptosis.

Aim of the study: Cardiovascular disease (CVD) seriously endangers human health and is characterized by high mortality and disability. The effectiveness of Dracocephalum moldavica L. in the treatment of CVD has been proven by clinical practice. However, the mechanism by which DML can treat CVD has not been systematically determined. Materials and methods: The active compounds in DML were screened by literature mining and pharmacokinetic analysis. Cytoscape software was used to construct the target-disease interaction network of DML in the treatment of CVD. Gene ontology and signalling pathway enrichment analyses were performed. The key target pathway network of DML compounds was constructed and verified by pharmacological experiments in vitro. A hydrogen glucose deprivation/reoxygenation model was established in H9c2 cells using hypoxia and glucose deprivation for 9 h combined with reoxygenation for 2 h. The model simulated myocardial ischaemic reperfusion injury to investigate the effects of total flavonoids of Cymbidium on cell viability, myocardial injury markers, oxidative stress levels, and reactive oxygen radical levels. Western blot analysis was used to examine NOX-4, Bcl-2/Bax, and PGC-1α protein expression. Results: Twenty-seven active components were screened, and 59 potential drug targets for the treatment of CVD were obtained. Through the compound-target interaction network and the target-disease interaction network, the key targets and key signalling pathways, such as NOX-4, Bcl-2/Bax and PGC-1α, were obtained. TFDM significantly decreased LDH and MDA levels and the production of ROS and increased SOD activity levels in the context of OGD/R injury. Further studies indicated that NOX-4 and Bax protein levels and the p-P38 MAPK/P38 MAPK andp-Erk1/2/Erk1/2 ratios were suppressed by TFDM. The protein expression of Bcl-2 and PGC-1α was increased by TFDM. Conclusions: Our results showed that DML had multicomponent, multitarget and multichannel characteristics in the treatment of CVD. The mechanism may be associated with the following signalling pathways: 1) the NOX-4/ROS/p38 MAPK signalling pathway, which inhibits inflammation and reactive oxygen species (ROS) production, and 2) the Bcl-2/Bax and AMPK/SIRT1/PGC-1α signalling pathways, which inhibit apoptosis. [ABSTRACT FROM AUTHOR]

The antibacterial activities of two previously reported copper (II) coordination complexes [Cu(HL1)Cl2] and [Cu(HL2)Cl2], and the two new complexes [Cu(HL3)Cl2] and [Cu(HL4)Cl2], where HL1 is 2-(((pyridin-2-ylmethyl)amino)methyl)phenol, HL2 is 2-((benzyl(pyridine-2-ylmethyl)amino)methyl)phenol, HL3 is 2-(((pyridin-2-ylethyl)amino)methyl)phenol and HL4 is 2-(((pyridin-2-ylmethyl)(quinolin-2-ylmethyl)-amino)methyl)phenol were investigated using agar well plate diffusion assay. The ligands were characterized using elemental analysis, IR, 1H-NMR, 13C-NMR spectroscopy and thermal analysis. The corresponding copper (II) complexes of each ligand were synthesized and characterized using elemental analysis, FT-IR and UV-Visible spectroscopy, electronic spectra and magnetic moment measurements, and thermal analysis. Additionally, a thorough investigation of the copper complexes as potent drug candidates was performed using web-based software SwissADME to predict their physicochemical and pharmacokinetics properties. All copper complexes were stable to air and moisture and showed excellent stability up to 200 °C. Electronic spectra of all copper complexes in methanol consisted of single band at 14,490–15,260 cm−1 depicting ligand field excitation (Cu (II) d–d band). Ligands were completely ineffective on gram positive bacteria; HL1 and HL3 showed moderate to high activity at concentration range of 0.2–1 mg/ml. Copper complexes were found to exhibit moderate to high activity against bacteria as compared to the ligands. SwissADME analysis of all copper (II) complexes justified their candidature as potential candidate for pharmaceutical applications. [ABSTRACT FROM AUTHOR]

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Heterocycles are a privileged motif that appears as a momentous objective in medicinal chemistry. An important class of compounds for drug discovery and design is indole and its derivatives, which have been examined for a variety of biological activities. Therefore, it is noteworthy in the modern progress of synthetic, medicinal chemistry; the last decade has been onlooker with a multitude of reports on several indole derivatives corroborating these chemical entities to be a renowned target for the discovery of new drugs. The current study includes brief natural sources of indole, and a new range of commercially available indole‐based drugs. Additionally, this review discusses the numerous facets of the structure‐activity relationship study (SARs) and provides information about the varied pharmacological effects of indole derivatives. The literature data presented for the anti‐pharmacological agents herein covers largely from the year 2015 to mid of 2022. [ABSTRACT FROM AUTHOR]

A new triol-based compound, teucriol (1) and eleven others (2–12), were first time isolated from the ethanol extract of Teucrium stocksianum Bioss using bioassay guidelines, and their structures were established using various spectroscopic techniques. Antibacterial, antifungal, insecticidal, cytotoxic, phytotoxic, and antioxidant properties of ethanol extract fractions and a novel isolate were tested. When compared to the standard ceftriaxone, the extract, fractions, and novel isolate demonstrated good antibacterial potential against Streptococcus pneumonia, Staphylococcus aureus, Klebsiella pneumonia and Escherichia coli bacteria, while all were inert against Fusarium solani, Candida albicans, Candida glabrata, Microsporum Canis and Aspergillus flavus fungi, and Tribolium castaneum and Rhyzopertha dominica insects. All fractions showed promising antioxidant activity. Density functional theory was used to optimize the ground state geometry of teucriol (1) at the B3LYP/TZ2P level. The global molecular descriptors, electronic characteristics, molecular electrostatic potential, and Hirshfeld surface analyses were studied to investigate the biological activity of the investigated molecule.

[Display omitted] • Nanocapsules presented better physicochemical characteristics than liposomes. • Chemical interactions between the drug and the nanostructure were observed. • Paroxetine hydrochloride-loaded liposomes showed slower in vitro release. • Liposomes showed a higher protective effect on Vero cells in vitro. • Antidepressant effect was maintained at a dose four times lower than the free drug. Depression is one of the most common psychiatric disorders. Nanotechnology has emerged to optimize the pharmacological response. Therefore, the aim of this work was to develop and characterize liposomes and nanocapsules containing paroxetine hydrochloride and evaluate their antidepressant-like effect using the open field and tail suspension tests in mice. Liposomes and nanocapsules were prepared using the reverse-phase evaporation and nanoprecipitation methods, respectively. The particle size of the formulation ranged from 121.81 to 310.73 nm, the polydispersity index from 0.096 to 0.303, the zeta potential from −11.94 to −34.50 mV, the pH from 5.31 to 7.38, the drug content from 80.82 to 94.36 %, and the association efficiency was 98 %. Paroxetine hydrochloride showed slower release when associated with liposomes (43.82 %) compared to nanocapsules (95.59 %) after 10 h. In Vero cells, in vitro toxicity showed a concentration-dependent effect for paroxetine hydrochloride nanostructures. Both nanostructures decreased the immobility time in the TST at 2.5 mg/kg without affecting the number of crossings in the open field test, suggesting the antidepressant-like effect of paroxetine. In addition, the nanocapsules decreased the number of groomings, reinforcing the anxiolytic effect of this drug. These results suggest that the nanostructures were effective in preserving the antidepressant-like effect of paroxetine hydrochloride even at low doses. [ABSTRACT FROM AUTHOR]

The damage to crops and food commodities by pests and diseases remains a major public health concern. Globally, investigations were carried out to develop harmless natural products from essential oils (EOs) and advances were made to meet users' acceptance as an alternative to chemical fungicides and insecticides. Recently, many EOs have shown potential results against a wide range of plant pathogens and insect pests, and are thus, attractive substitutes to synthetic chemicals. Remarkably, EOs based commercial pesticides remain lesser in number and this opens several prospects for their claim for use in present agriculture. The present paper provides a summary of the current status and prospects in evaluating the efficiency of the use of EO of Dysphania ambrosioides (L.) Mosyakin & Clemants syn. Chenopodium ambrosioides L. (Mexican tea) belonging to the family Amaranthaceae, in crop protection strategies against plant pathogens and insect pests, considering the opportunities and problems linked with the prospects of sustainable environment-friendly agriculture in the future. In addition, the chemical composition of D. ambrosioides EO from different geographical regions along with the pharmacological application, probable modes of action, and indication for or against the use of this EO as an alternative to chemicals, in several applications have been discussed. The EO of D. ambrosioides possessed potential pharmacological activities, such as antitumor, antiprotozoal, allelopathic, antiviral, immunoregulatory, anti-inflammatory, and antioxidant activities. Most of the chemically characterized EO of D. ambrosioides contained ascaridole, α-terpinene, p-cymene, and caryophyllene oxide as major components, and have shown efficient antibacterial, antifungal, and insecticidal activities against pests and pathogens of economically important crops. Thus, the EO of D. ambrosioides and its major constituents can be utilized as potential botanical pesticides for crop protection after large-scale evaluation. [ABSTRACT FROM AUTHOR]

Thioureas and their derivatives are organosulfur compounds having applications in numerous fields such as organic synthesis and pharmaceutical industries. Symmetric thiourea derivatives were synthesized by the reaction of various anilines with CS2. The synthesized compounds were characterized using the UV-visible and nuclear magnetic resonance (NMR) spectroscopic techniques. The compounds were screened for in vitro inhibition of α-amylase, α-glucosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) enzymes and for their antibacterial and antioxidant potentials. These compounds were fed to Swiss male albino mice to evaluate their toxicological effects and potential to inhibit glucose-6-phosphatase (G6Pase) inhibition. The antibacterial studies revealed that compound 4 was more active against the selected bacterial strains. Compound 1 was more active against 2,2-diphenyl-1-picrylhydrazyl and 2,2’-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals, AChE, BuChE, and α-glucosidase. Compound 2 was more potent against α-amylase and G6Pase. Toxicity studies showed that compound 4 is safe as it exerted no toxic effect on any of the hematological and biochemical parameters or on liver histology of the experimental animals at any studied dose rate. The synthesized compounds showed promising antibacterial and antioxidant potential and were very active (both in vitro and in vivo) against G6Pase and moderately active against the other selected enzymes used in this study.

Background: The outbreak of new coronavirus has tremendously threatened the public health system worldwide, including China. Chinese patent medicines (CPMs) have greatly contributed to the prevention and treatment of this viral infection, as well as the recovery of patients with COVID-19 infection. Therefore, numerous experts and guidelines recommend to take CPMs to treat pneumonia due to COVID-19. Aim of the Study: The present study reviewed CPMs recommended by the < Guidelines for diagnosis and management of COVID-19 (8th edition)> regarding evidence of their efficacy from clinical studies and the underlying mechanisms, which will lay the foundation for clinical use of these CPMs for COVID-19. Methods: The composition, efficacy, indications, history of use, and relevant clinical research on 14 recommended CPMs, including Huoxiangzhengqi capsules (pills, liquid, oral solution), Jinhuaqinggan granules, Lianhuaqingwen capsules (granules), Shufengjiedu capsules, Xiyanping injections, Xuebijing injections, Reduning injections, Tanreqing injections, Xingnaojing injections, Shenfu injections, Shengmai injections, Angongniuhuang pills, Suhexiang pills, were searched in both Chinese and English databases based on differences in stages of the disease and manifestations of such patients. Advantages of these CPMs over conventional treatments and their underlying mechanisms were explored by analyzing results from published articles and undergoing clinical trials. Results: Findings from clinical studies and Chinese experience in using these CPMs showed that CPMs, when used in combination with conventional treatments, were effective in managing COVID-19 with few side effects. Conclusion: CPMs have excellent efficacy in managing COVID-19 with a great potential for clinical use. [ABSTRACT FROM AUTHOR]

Background: The outbreak of new coronavirus has tremendously threatened the public health system worldwide, including China. Chinese patent medicines (CPMs) have greatly contributed to the prevention and treatment of this viral infection, as well as the recovery of patients with COVID-19 infection. Therefore, numerous experts and guidelines recommend to take CPMs to treat pneumonia due to COVID-19.Aim of the Study: The present study reviewed CPMs recommended by the < Guidelines for diagnosis and management of COVID-19 (8th edition)> regarding evidence of their efficacy from clinical studies and the underlying mechanisms, which will lay the foundation for clinical use of these CPMs for COVID-19.Methods: The composition, efficacy, indications, history of use, and relevant clinical research on 14 recommended CPMs, including Huoxiangzhengqi capsules (pills, liquid, oral solution), Jinhuaqinggan granules, Lianhuaqingwen capsules (granules), Shufengjiedu capsules, Xiyanping injections, Xuebijing injections, Reduning injections, Tanreqing injections, Xingnaojing injections, Shenfu injections, Shengmai injections, Angongniuhuang pills, Suhexiang pills, were searched in both Chinese and English databases based on differences in stages of the disease and manifestations of such patients. Advantages of these CPMs over conventional treatments and their underlying mechanisms were explored by analyzing results from published articles and undergoing clinical trials.Results: Findings from clinical studies and Chinese experience in using these CPMs showed that CPMs, when used in combination with conventional treatments, were effective in managing COVID-19 with few side effects.Conclusion: CPMs have excellent efficacy in managing COVID-19 with a great potential for clinical use.

Abstract Background Saussurea obvallata (DC.) Edgew. (S. obvallata) is an endangered medicinal herb of the high altitude Himalayan region with immense cultural significance. This study is one of the first report of pharmacological evaluation and GC-MS analysis of methanolic extracts of leaves and flowers of S. obvallata. Methods Total flavonoid content (TFC) and total phenolic content (TPC) were performed according to standard protocols. The antioxidant activities of both the extracts (methanol and aqueous) were examined using two complementary methods, namely diphenylpicrylhydrazyl (DPPH) and Hydrogen peroxide (H2O2) assay. While, antimicrobial potential examined by using classical assays on pathogenic microbial strains along with appropriate controls of antimicrobial agents. Gas Chromatographic-Mass Spectrometric analyses of methanolic extracts of S. obvallata were performed for the identification of bioactive components. Statistical analysis was performed by using SPSS version 16.0. Results The extracts of leaves and flowers of S. obvallata showed significant results for all pharmacological experiments. TPC was recorded from a range of 132.67 ± 0.17 to 358.67 ± 0.17 mg GAE gm− 1 dw while TFC was recorded from a range of 65.73 ± 1.55 to 326.88 ± 2.11 mg QE gm− 1 dw. Per cent DPPH free radical scavenging activity was recorded from a range of 29.25 ± 0.86 to 82.88 ± 0.48% whereas per cent H2O2 free radical scavenging activity were recorded from a range of 39.75 ± 0.36 to 41.05 ± 0.46%. Antimicrobial activity was analyzed against four bacterial strains and three fungal strains. S. obvallata extracts showed fine zone of inhibition against Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus, but Escherichia coli showed resistant (in terms of lower zone) against the extract compared to three bacteria. In antifungal activity, extract showed maximum zone of inhibition against Candida glabrata followed by Candida albicans and Candida tropicalis. GC-MS analysis of methanolic extracts of leaves and flowers of S. obvallata showed the presence of 36 and 48 components, respectively, based on retention time (Rt), and area per cent. Conclusion These findings confirm the traditional claims and contribute in providing promising baseline information for the pharmacological use of S. obvallata. Additional highly developed research is essential for isolation and identification of specific active components which are responsible for pharmacological properties of the plant.

To improve the liposolubility and blood-brain barrier permeability of magnoflorine, a new formulation of magnoflorine-phospholipid complex was prepared, characterized, and pharmacologically evaluated in the chronic unpredictable mild stress animal model. In this paper, the magnoflorine-phospholipid complex was synthesized and its characterization was determined. The antidepressant-like and antioxidant activity of magnoflorine-phospholipid complex was investigated by behavioral tests and western blotting analysis. As a result, the magnoflorine-phospholipid complex displayed high encapsulation efficiency and significantly improved the oil-water participate coefficient. In vivo blood-brain distribution study, the magnoflorine-phospholipid complex extended the duration of magnoflorine in blood and help magnoflorine to permeate the blood-brain barrier into brain. In behavioral tests, the magnoflorine-phospholipid complex significantly decreased immobility time compared to model control group in both FST and TST. Furthermore, the magnoflorine-phospholipid complex increased the expression of antioxidative stress-related proteins by the western blotting analysis. These findings strongly suggest that the phospholipid complex could significantly improve liposolubility, drug properties of magnoflorine and help magnoflorine permeate blood-brain barrier and exert the antidepressant effect.

This proposal would synthesize the work on arylpiperazine derivatives because aryl piperazine has the largest amount of positive effects on the biological screen of the heterocyclic and its congeners as the most important building blocks for drug development. Two separate series of N-(4-(benzo[d]oxazol-2-yl)phenyl)-2-[4-(arylsubstituted) piperazines-1-yl]acetamide and 2-[4-(arylsubstitution)piperazine-1-yl]acetamide are synthesized and are distinguished by various substituents of aryl piperzine, such as a melting point determination and chromatography in thin-scale (TLC). Two different series are also performed, synthesized and characterized. Its spectroscopic characterisation was undertaken for their structure elucidation. Followed by this, synthesized drugs can be pharmacologically assessed. In pharmacological research, the inhibition of 5-hydoxytraphtophen (5-HTP) mediated head twitches, the inhibition of the behaviour, and the activation of cataleptic disorder are determined by the behaviours. [ABSTRACT FROM AUTHOR]

Abstract Respiratory disorders are a common cause of malady and demise in Pakistan due to its remoteness, cold and harsh climatic conditions as well as scarce health care facilities. The people rely upon the indigenous plant resources to cure various respiratory disorders. The primary objective of this review was to assemble all available ethno-medicinal data of plants used for respiratory disorders in Pakistan. Pharmacological activity of these plants (based upon published scientific research), distribution, diversity, use, preparation methods, economical value, conservation status and various available herbal products of some plants have also been explored. This study scrutinized various electronic databases for the literature on medicinal plants used in Pakistan to treat respiratory disorders. A total of 384 species belonging to 85 families used to treat respiratory disorders in Pakistan has been documented. Cough was the disorder treated by the highest number of species (214) followed by asthma (150), cold (57) and bronchitis (56). Most of the plants belongs to Asteraceae (32) and Solanaceae family (32) followed by moraceae (17), Poaceae (13), and Amaranthaceae (13) with their habit mostly of herb (219) followed by Shrub (112) and tree (69). Traditional healers in the region mostly prepare ethno medicinal recipes from leaves (24%) and roots (11%) in the form of decoction. Among the reported conservation status of 51 plant species, 5 were endangered, 1 critically endangered, 11 vulnerable, 14 rare, 16 least concern, 3 infrequent and 1 near threatened. We found only 53 plants on which pharmacological studies were conducted and 17 plants being used in herbal products available commercially for respiratory disorders. We showed the diversity and importance of medicinal plants used to treat respiratory disorders in the traditional health care system of Pakistan. As such disorders are still causing several deaths each year, it is of the utmost importance to conduct phytochemical and pharmacological studies on the most promising species. It is also crucial to increase access to traditional medicine, especially in rural areas. Threatened species need special attention for traditional herbal medicine to be exploited sustainably.

Phytochemical and pharmacological investigations of leaves of Praecitrullus fistulosus for the antidiabetic activity have been done in our research work encompassed in depth and systematic screening of plant leaves and further extraction, characterization and bioevaluation. The research was envisaged for antidiabetic activity of different extracts procured by successive extraction methods and to find out or isolate the most possible active compounds from the active extracts showing the best activity. The antidiabetic activity of all extracts has been evaluated by STZ induced diabetes. The isolated compounds have been evaluated by in-vitro and in-vivo models. The alcohol soluble extractives values were found to be higher than water soluble extractive value. Alcohol being a moderately non polar solvent, able to extract polar and non-polar components yields higher extractive value. The ethanol extract shows significant enhancement in glucose tolerance in glucose fed hyperglycemic normal rats and produced a marked decrease in blood glucose levels at 200 mg/kg and 400 mg/kg body weight in streptozotocin-diabetic rats after 21 days treatment. [ABSTRACT FROM AUTHOR]

To improve the liposolubility and blood-brain barrier permeability of magnoflorine, a new formulation of magnoflorine-phospholipid complex was prepared, characterized, and pharmacologically evaluated in the chronic unpredictable mild stress animal model. In this paper, the magnoflorine-phospholipid complex was synthesized and its characterization was determined. The antidepressant-like and antioxidant activity of magnoflorine-phospholipid complex was investigated by behavioral tests and western blotting analysis. As a result, the magnoflorine-phospholipid complex displayed high encapsulation efficiency and significantly improved the oil-water participate coefficient. In vivo blood-brain distribution study, the magnoflorine-phospholipid complex extended the duration of magnoflorine in blood and help magnoflorine to permeate the blood-brain barrier into brain. In behavioral tests, the magnoflorine-phospholipid complex significantly decreased immobility time compared to model control group in both FST and TST. Furthermore, the magnoflorine-phospholipid complex increased the expression of antioxidative stress-related proteins by the western blotting analysis. These findings strongly suggest that the phospholipid complex could significantly improve liposolubility, drug properties of magnoflorine and help magnoflorine permeate blood-brain barrier and exert the antidepressant effect. [ABSTRACT FROM AUTHOR]

(1) Background: Two first-in-class racemic dopamine D1 receptor (D1R) positive allosteric modulator (PAM) chemotypes (1 and 2) were identified from a high-throughput screen. In particular, due to its selectivity for the D1R and reported lack of intrinsic activity, compound 2 shows promise as a starting point toward the development of small molecule allosteric modulators to ameliorate the cognitive deficits associated with some neuropsychiatric disease states; (2) Methods: Herein, we describe the enantioenrichment of optical isomers of 2 using chiral auxiliaries derived from (R)- and (S)-3-hydroxy-4,4-dimethyldihydrofuran-2(3H)-one (d- and l-pantolactone, respectively); (3) Results: We confirm both the racemate and enantiomers of 2 are active and selective for the D1R, but that the respective stereoisomers show a significant difference in their affinity and magnitude of positive allosteric cooperativity with dopamine; (4) Conclusions: These data warrant further investigation of asymmetric syntheses of optically pure analogues of 2 for the development of D1R PAMs with superior allosteric properties.

Hepatocellular carcinoma (HCC) is a kind of complicated disease with an increasing incidence all over the world. A classic Chinese medicine formula, Zuojin pill (ZJP), was shown to exert therapeutic effects on HCC. However, its chemical and pharmacological profiles remain to be elucidated. In the current study, network pharmacology approach was applied to characterize the action mechanism of ZJP on HCC. All compounds were obtained from the corresponding databases, and active compounds were selected according to their oral bioavailability and drug-likeness index. The potential proteins of ZJP were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database and the traditional Chinese medicine integrated database (TCMID), whereas the potential genes of HCC were obtained from OncoDB.HCC and Liverome databases. The potential pathways related to genes were determined by gene ontology (GO) and pathway enrichment analyses. The compound-target and target-pathway networks were constructed. Subsequently, the potential underlying action mechanisms of ZJP on HCC predicted by the network pharmacology analyses were experimentally validated in HCC cellular and orthotopic HCC implantation murine models. A total of 224 components in ZJP were obtained, among which, 42 were chosen as bioactive components. The compound-target network included 32 compounds and 86 targets, whereas the target-pathway network included 70 proteins and 75 pathways. The in vitro and in vivo experiments validated that ZJP exhibited its prominent therapeutic effects on HCC mainly via the regulation of cell proliferation and survival though the EGFR/MAPK, PI3K/NF-κB, and CCND1 signaling pathways. In conclusion, our study suggested combination of network pharmacology prediction with experimental validation may offer a useful tool to characterize the molecular mechanism of traditional Chinese medicine (TCM) ZJP on HCC.

Background: Hepatocellular carcinoma (HCC) is a common clinical malignant tumor of the digestive system. Hu-Qi-Zheng-Xiao (HQZX) decoction has been clinically found to prolong the survival of patients with hepatocellular carcinoma and improve the quality of patients' survival, but its antitumor biological mechanism is still unclear., Methods: A nude mouse hollow fiber hepatocellular carcinoma model was constructed to analyze the in vivo efficacy of HQZX decoction against 7 different hepatocellular carcinoma cells. The subcutaneous graft tumor model was again validated. In vitro, the effect of HQZX decoction on the growth and metastasis of the cell line with the highest growth inhibition was evaluated. The cell line with the best efficacy response screened was again used to construct a hollow fiber hepatocellular carcinoma model and hollow fiber conduit cells were extracted to detect the expression of HIF-1α, VEGF, EMT-related molecules, LCSCs-related molecules, and to observe the density of the subcutaneous vascular network of hollow fiber conduits. The liver metastasis model of splenic injection was constructed to observe the effect of HQZX decoction on tumor metastasis., Results: The hollow fiber hepatocellular carcinoma model was evaluated for the efficacy of HQZX decoction, and it was found to have the highest growth inhibition of LM3-luc cells. In vitro, the CCK8 assay revealed that HQZX decoction could inhibit tumor migration and invasion and promote apoptosis. In addition, the mechanism study of extracting cells from hollow fiber tubes found that HQZX decoction could inhibit metastasis-associated HIF-1α, VEGF, EMT-related molecules, and LCSCs-related molecules expression. capillary network around subcutaneous fiber tubes was reduced in the HQZX decoction gavage group of mice. It inhibited tumor metastasis in nude mice., Conclusions: HQZX decoction inhibited the growth of a variety of hepatocellular carcinoma cells. HQZX decoction suppressed the expression of metastasis-associated VEGF, EMT-related molecules, and LCSCs-related molecules and inhibited tumor angiogenesis and growth and metastasis, which may be related to the inhibition of the HIF-1α signaling pathway. It reveals that HQZX decoction may be a promising herbal compound for anti-HCC therapy, and also reveals the accurate feasibility of the hollow fiber hepatocellular carcinoma model for in vivo pharmacodynamic evaluation and mechanism study., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hepatocellular carcinoma (HCC) is a kind of complicated disease with an increasing incidence all over the world. A classic Chinese medicine formula, Zuojin pill (ZJP), was shown to exert therapeutic effects on HCC. However, its chemical and pharmacological profiles remain to be elucidated. In the current study, network pharmacology approach was applied to characterize the action mechanism of ZJP on HCC. All compounds were obtained from the corresponding databases, and active compounds were selected according to their oral bioavailability and drug-likeness index. The potential proteins of ZJP were obtained from the traditional Chinese medicine systems pharmacology (TCMSP) database and the traditional Chinese medicine integrated database (TCMID), whereas the potential genes of HCC were obtained from OncoDB.HCC and Liverome databases. The potential pathways related to genes were determined by gene ontology (GO) and pathway enrichment analyses. The compound-target and target-pathway networks were constructed. Subsequently, the potential underlying action mechanisms of ZJP on HCC predicted by the network pharmacology analyses were experimentally validated in HCC cellular and orthotopic HCC implantation murine models. A total of 224 components in ZJP were obtained, among which, 42 were chosen as bioactive components. The compound-target network included 32 compounds and 86 targets, whereas the target-pathway network included 70 proteins and 75 pathways. The in vitro and in vivo experiments validated that ZJP exhibited its prominent therapeutic effects on HCC mainly via the regulation of cell proliferation and survival though the EGFR/MAPK, PI3K/NF-κB, and CCND1 signaling pathways. In conclusion, our study suggested combination of network pharmacology prediction with experimental validation may offer a useful tool to characterize the molecular mechanism of traditional Chinese medicine (TCM) ZJP on HCC. [ABSTRACT FROM AUTHOR]

Hypertension is a major risk factor for human cardiovascular health, which can damage heart, brain, kidneys, etc. In this study we aimed to develop novel angiotensin II receptor blockers (ARBs) that prevent the increase of blood pressure for treatment of hypertension. (2-(4-((2-Amyl-5-nitro-1H-benzo[d]-imidazol-1-yl) methyl)-1H-indol-1-yl) tetrazole; compound 1a) was one of the ARBs designed and synthesized. It was prepared and orally administered to spontaneous hypertensive rats to study the antihypertensive effects. The maximum reduction in blood pressure reached 50 mmHg after dosing compound 1a for 5 h. Acute toxicity test was carried out on healthy 4 week old 30 male and 30 female ICR mice and LD50 for 1a was found to be 2864.03 mg/kg. High performance liquid chromatography was employed to determine the level of 1a plasma concentration at various time points after administration. The plasma concentration of 1a increased after 2 h, declined gradually and was still detectable in the plasma after 72 h. The drug distribution analysis of 1a was performed on healthy Wistar rats. It was present in the liver with the highest concentration, in kidney with a lower concentration, and in the spleen, lung, heart and brain with the lowest concentration. It displayed high affinity to AT1 receptor, and had an efficient and long-lasting effect in reducing blood pressure, which lasted for more than 12 h. Due to its biological safety, 1a could be absorbed quickly, metabolized smoothly, and can be distributed in important organs. Therefore, 1a could be considered as a suitable ARB candidate for further studies. [ABSTRACT FROM AUTHOR]

The development of reliable and green methods for the fabrication of metallic nanoparticles (NPs) has many advantages in the field of nanotechnology. In this direction, the present work describes an eco‐friendly and cost‐effective protocol for the production of silver NPs (AgNPs) using an aqueous extract of Quercus semecarpifolia leaves. Different techniques were carried out for the characterisation of the synthesised AgNPs. The ultraviolet–visible spectroscopic analysis showed the highest absorbance peak at 430 nm. The particle size and structure were confirmed by scanning electron microscopy as well as transmission electron microscopy (TEM) analysis. From TEM imaging, it was revealed that the formed particles were spherical with an average size of 20–50 nm. The crystalline nature of the NPs was determined by X‐ray powder diffraction patterns. Thermogravimetry and differential thermal analysis were also evaluated by a temperature increment from 100 to 1000°C. Bio‐inspired synthesis of AgNPs was performed for their pharmacological evaluation in relation to the activities of the crude methanolic, n ‐hexane, chloroform, ethyl acetate, and aqueous extracts. Good cytotoxic activity was exhibited by the green‐synthesised AgNPs (77%). Furthermore, the AgNPs were found to exhibit significant antioxidant activity at 300 μg/ml (82%). The AgNPs also exhibited good phytotoxic potential (75%). [ABSTRACT FROM AUTHOR]

Descurainia sophia is widely distributed in China and is one of the most troublesome annual weeds. It has diverse medicinal usage. D. sophia has abundant oil, making it an important oil plant in China. The main goal of this study was to obtain the maximum yield of the oil by an optimal selection of supercritical fluid extraction parameters. According to the central composite design and response surface methodology for supercritical fluid extraction method, a quadratic polynomial model was used to predict the yield of D. sophia seed oil. A series of runs was performed to assess the optimal extraction conditions. The results indicated that the extraction pressure had the greatest impact on oil yield within the range of the operating conditions studied. A total of approximately 67 compounds were separated in D. sophia seed oil by GC-MS, of which 51 compounds represented 98.21% of the total oils, for the first time. This study was also aimed at evaluating the anti-asthmatic, anti-tussive and expectorant activities in vivo of D. sophia seed oil which supplied for further research on bioactive constituents and pharmacological mechanisms.

In quest to develop effective anticancer drugs, a series of twelve heterocycles ( 1 − 12 ) embedded with oxopyrrolidine rings was synthesized. The compounds ( 1 – 12 ) were characterized by microanalysis, FT-IR, UV–Vis and 1 H NMR spectroscopy, and mass spectrometry. Experimental DNA binding and computational docking studies were carried out to identify the biological targets of 1 – 12 . The values of DNA binding constants of 1 – 12 ranged from 1.5 × 10 4 to 4.0 × 10 5 M − 1 . The docking energies of the DNA-compound adducts varied from − 23.84 to − 30.96 kJ/mol, and the adducts were stabilized by H-bonding and hydrophobic attractions. The compounds preferred to enter minor grooves of DNA during adduct formation. Cytotoxicity studies of 1 – 12 were carried out towards both cancerous and normal cell lines. Compounds 4 , 6 , 7 , 8 , 9 , 10 , 11 and 12 at 1.0 nM concentration exhibited good anticancer activities with cell viabilities in the range of 19–110% against breast (MCF-7) and microglial (BV-2) cancer cell lines. The potency of 1 – 12 as future anticancer agents was ascertained by drug likeness using Lipinski's rule of five. It was observed that 1 – 12 obeyed the ‘Rule of Five’ with logP values < 5 and HBAs ≤ 7. All the results taken together indicated good pharmacological properties of the prepared heterocycles, and thus their further biological evaluation towards other cancer cell lines is warranted. [ABSTRACT FROM AUTHOR]

The second International Electronic Conference on Medicinal Chemistry, organized and sponsored by the publisher MDPI AG and the Journal Pharmaceuticals, took place in November 2016 on the SciForum website (www.sciforum.net/conference/ecmc-12). More than 150 authors from 22 countries participated in the event. Selected works presented during the scientific meeting are disclosed in this report. [ABSTRACT FROM AUTHOR]

Baclofen (1) is a potent and selective agonist for bicuculline-insensitive GABAB receptors and is used clinically as an antispastic and muscle relaxant agent. In the search for new bioactive chemical entities that bind specifically to GABAB receptors, we report here the synthesis of certain baclofen homologues, namely (R,S)-5-amino-3-arylpentanoic acid hydrochlorides (R,S)-1a–h as well as (R,S)-5-amino-3-methylpentanoic acid [(RS)-1i] to be evaluated as GABABR agonists. Compound 1a is an agonist to GABAB receptors with an EC50 value of 46 μM on tsA201 cells transfected with GABAB1b/GABAB2/Gqz5, being the most active congener among all the synthesized compounds.

The first International Electronic Conference on Medicinal Chemistry, organized and sponsored by MDPI AG, publisher, and the Journal Pharmaceuticals, took place in November 2015 on the SciForum website. More than 200 authors from 18 countries participated in the event and was attended by 25,000 visitors who had the opportunity to browse among 55 presentations, keynotes, and videos. A short description of some works presented during that scientific meeting is disclosed in this report. [ABSTRACT FROM AUTHOR]

The second International Electronic Conference on Medicinal Chemistry, organized and sponsored by the publisher MDPI AG and the Journal Pharmaceuticals, took place in November 2016 on the SciForum website (www.sciforum.net/conference/ecmc-12). More than 150 authors from 22 countries participated in the event. Selected works presented during the scientific meeting are disclosed in this report.

CR-LAAO is an l -amino acid oxidase from Calloselasma rhodostoma snake venom that has been broadly studied regarding its structural and biochemical characteristics, however, few studies have investigated its pharmacological effects. The present study aimed at the evaluation of the biotechnological potential of CR-LAAO by determining its bactericidal, antifungal, leishmanicidal and trypanocidal activity, as well as its cytotoxicity on human tumor and non-tumor cell lines. After 24 h of preincubation, CR-LAAO showed bactericidal effects against both Staphylococcus aureus (MIC 0.78 μg/mL) and Escherichia coli (MIC 31.25 μg/mL) strains, inducing dismantle of bacterial cell walls. After 6 h of preincubation with Candida albicans , CR-LAAO was able to inhibit 80% of the yeast growth, and it also showed cytotoxic activity on Leishmania species and Trypanosoma cruzi . Additionally, CR-LAAO showed high cytotoxicity on HepG2 and HL-60 tumor cells (IC 50 10.78 and 1.7 μg/mL), with lower effects on human mononuclear cells (PBMC). The cytotoxic effects of CR-LAAO were significantly inhibited in the presence of catalase, which suggests the involvement of hydrogen peroxide in its mechanisms of toxicity. Therefore, CR-LAAO showed promising pharmacological effects, and these results provide important information for the development of therapeutic strategies with directed action, such as more effective antimicrobial agents. [ABSTRACT FROM AUTHOR]

Descurainia sophia is widely distributed in China and is one of the most troublesome annual weeds. It has diverse medicinal usage. D. sophia has abundant oil, making it an important oil plant in China. The main goal of this study was to obtain the maximum yield of the oil by an optimal selection of supercritical fluid extraction parameters. According to the central composite design and response surface methodology for supercritical fluid extraction method, a quadratic polynomial model was used to predict the yield of D. sophia seed oil. A series of runs was performed to assess the optimal extraction conditions. The results indicated that the extraction pressure had the greatest impact on oil yield within the range of the operating conditions studied. A total of approximately 67 compounds were separated in D. sophia seed oil by GC-MS, of which 51 compounds represented 98.21% of the total oils, for the first time. This study was also aimed at evaluating the anti-asthmatic, anti-tussive and expectorant activities in vivo of D. sophia seed oil which supplied for further research on bioactive constituents and pharmacological mechanisms. [ABSTRACT FROM AUTHOR]

A new triol-based compound, teucriol (1) and eleven others (2 – 12), were first time isolated from the ethanol extract of Teucrium stocksianum Bioss using bioassay guidelines, and their structures were established using various spectroscopic techniques. Antibacterial, antifungal, insecticidal, cytotoxic, phytotoxic, and antioxidant properties of ethanol extract fractions and a novel isolate were tested. When compared to the standard ceftriaxone, the extract, fractions, and novel isolate demonstrated good antibacterial potential against Streptococcus pneumonia , Staphylococcus aureus , Klebsiella pneumonia and Escherichia coli bacteria, while all were inert against Fusarium solani, Candida albicans, Candida glabrata, Microsporum Canis and Aspergillus flavus fungi, and Tribolium castaneum and Rhyzopertha dominica insects. All fractions showed promising antioxidant activity. Density functional theory was used to optimize the ground state geometry of teucriol (1) at the B3LYP/TZ2P level. The global molecular descriptors, electronic characteristics, molecular electrostatic potential, and Hirshfeld surface analyses were studied to investigate the biological activity of the investigated molecule. [ABSTRACT FROM AUTHOR]

Substituted thiadiazines exert a reliable therapeutic effect in treating stress, and a schematic description of their ability to influence all aspects of a stress response has been depicted. This study was conducted to pharmacologically evaluate compound L-17, a substituted thiadiazine, (2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide) for possible anti-psychotic/antidepressant activity. Compound L-17 was synthesized by cyclocondensation of α-bromoacetophenone with the original morpholine-4-carbothionic acid hydrazide. Pharmacologic evaluations were conducted using methods described by E.F. Lavretskaya (1985), and in accordance with published guidelines for studying drugs for neuroleptic activity. Compound L-17 was evaluated for various possible mechanisms of action, including its effects on cholinergic system agonists/antagonists, dopaminergic neurotransmission, the adrenergic system, and 5-HT3 serotonin receptors. One or more of these mechanisms may be responsible for the beneficial effects shown by thiadiazine compounds in experiments conducted to evaluate their activity in models of acute stress and acute myocardial infarction.

The first International Electronic Conference on Medicinal Chemistry, organized and sponsored by MDPI AG, publisher, and the Journal Pharmaceuticals, took place in November 2015 on the SciForum website. More than 200 authors from 18 countries participated in the event and was attended by 25,000 visitors who had the opportunity to browse among 55 presentations, keynotes, and videos. A short description of some works presented during that scientific meeting is disclosed in this report.

Highlights: [•] Substituted halopyrimidine derivatives are used in colorectal cancer chemotherapy. [•] 5-Fluorouracil plays a crucial role in Food and Drug Administration systems. [•] The metal complexes show homogeneous morphology with microcrystalline environment. [•] Gel electrophoresis shows CT DNA undergoes oxidative cleavage with the complexes. [•] In vitro antimicrobial and antioxidant assessments show high inhibiting potential. [ABSTRACT FROM AUTHOR]

Abstract: This article describes the design of biphenyl moiety linked with aryl piperazine and syntheses of fourteen 1-(biphenyl-4-yl)-2-[4-(substituted phenyl)-piperazin-1-yl]ethanone derivatives along with their pharmacological evaluation for antipsychotic activity and computational studies including quantitative structure activity relationship (QSAR) and descriptor based similarity study. All compounds were found to exhibit considerable anti-dopaminergic and anti-serotonergic activity in behavioural models. Among all derivatives, compound 1-(biphenyl-4-yl)-2-[4-(2-methoxyphenyl)-piperazin-1-yl]ethanone (3c) and 1-(biphenyl-4-yl)-2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]ethanone (3k) showed impressive antipsychotic profile with lower potency for catalepsy induction. These results were found to be sturdily matching with docking study in designing of compounds with homology model of human dopamine D2 receptor. Also the QSAR study strongly supports the obtained results. [Copyright &y& Elsevier]