Bioengineered synthesis of phytochemical-adorned green silver oxide (Ag2O) nanoparticles via Mentha pulegium and Ficus carica extracts with high antioxidant, antibacterial, and antifungal activities.

Silver oxide nanoparticles have various biomedical and pharmaceutical applications. However, conventional nanofabrication of Ag2O is associated with the use of toxic chemicals and organic solvents. To circumvent this hurdle, herein silver oxide quantum dots (Ag2O-QDs) were synthesized quickly (3 min) via the use of ultrasonic irradiation and plant-extract. Additionally, due to ultrasonic irradiation's effect on cell-wall destruction and augmentation of extraction efficiency, ultrasonic was also used in the preparation of Mentha pulegium and Ficus carica extracts (10 min, r.t) as natural eco-friendly reducing/capping agents. The UV-Vis result indicated a broad absorption peak at 400-500 nm. TEM/SEM analysis showed that ultrasound introduced a uniform spherical particle and significantly reduced particle size compared to the conventional heating method (∼ 9 nm vs. ∼ 100 nm). Silver and oxygen elements were found in the bio-synthesized Ag2O by EDS. The FTIR and phenol/flavonoid tests revealed the presence of phenol and flavonoid associated with the nanoparticles. Moreover, nanoparticles exhibited antioxidant/antibacterial/antifungal activities. The MIC and MBC results showed the Ag2O QDs synthesized with M. pulegium extract have the highest antibacterial activity against E. coli (MBC = MIC:15.6 ppm), which were significantly different from uncoated nanoparticles (MBC = MIC:500 ppm). The data reflects the role of phyto-synthesized Ag2O-QDs using ultrasonic-irradiation to develop versatile and green biomedical products.

Drug design strategies for the treatment azole-resistant candidiasis.

INTRODUCTION: Despite the availability of novel antifungals and therapeutic strategies, the rate of global mortality linked to invasive fungal diseases from fungal infection remains high. Candida albicans account for the most invasive mycosis produced by yeast. Thus, the current arsenal of medicinal chemists is focused on finding new effective agents with lower toxicity and broad-spectrum activity. In this review article, recent efforts to find effective agents against azole-resistant candidiasis, a common fungal infection, are covered. AREAS COVERED: Herein, the authors outlined all azole-based compounds, dual target, and new scaffolds (non-azole-based compounds) which were effective against azole-resistant candidiasis. In addition, the mechanism of action and SAR studies were also discussed, if the data were available. EXPERT OPINION: The current status of fungal infections and the drawbacks of existing drugs have encouraged scientists to find novel scaffolds based on different methods like virtual screening and fragment-based drug discovery. Machine learning and in-silico methods have found their role in this field and experts are hopeful to find novel scaffolds/compounds by using these methods.

Polysaccharide-based hydrogels containing herbal extracts for wound healing applications.

Development of an ideal wound dressing with effective function for healing various types of wounds is the ultimate desire of the researchers. Natural-based compounds such as polysaccharides and phytochemicals offer useful properties making them perfect candidates for wound management. Polysaccharides-based hydrogels with an interconnected three-dimensional network, and desired properties have great potential as a carrier for delivery of different herbal extracts for oral and topical applications. Herbal extracts are extensively used for wound healing purposes, individually or in combination with other active agents. This study summarizes the current knowledge acquired on the preparation, functionalizing, and application of different kinds of polysaccharide-based hydrogels enriched by herbal extracts for different wound healing applications. The structural, biological, and functional impact of the polysaccharides and herbal extracts on the final hydrogel characteristics, as well as their influence on the different phases of the wound healing process have been discussed.

Formulation and evaluation of targeted nanoparticles for breast cancer theranostic system.

Theranostic polymeric NPs developed for both cancer diagnosis and cancer therapy. This multifunctional polymeric vehicle was prepared by a single emulsion evaporation method, using carboxyl-terminated PLGA. LHRH as a targeting moiety, was conjugated to the surface of polymeric carrier by applying polyethylene glycol. The results indicated that the diameter of NPs was ~185.4±4.6nm as defined by DLS. The entrapment efficacy of docetaxel, silibinin, and SPIONs was 84.6±4.1%, 80.6±2.7%, and 77.9±4.3%, respectively. The NPs showed a triphasic in-vitro drug release pattern. MTT assay was done on two cell lines, MCF-7 and SKOV-3. Enhanced cellular uptake ability of the targeted NPs to MCF-7 was evaluated in-vitro by confocal laser scanning microscopy. The results indicated that compared to non-targeted NPs, the LHRH targeted NPs had significant efficacy at IC50 concentration. The effect of the NPs on VEGF expression in MCF-7 and SKOV-3 cells was investigated by Real-Time PCR method. VEGF mRNA level expression in MCF-7 cell line reduced by 83% in comparison to control cell line. The designed NPs can be used as promising multifunctional platform for detection and targeted drug delivery in breast cancer.

Treatment of Helicobacter pylori infection: Current and future insights.

Helicobacter pylori (H. pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide. H. pylori treatment still remains a challenge, since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance, mucosal drug concentration, patient compliance, side-effect profile and cost. While no new drug has been developed, current therapy still relies on different mixture of known antibiotics and anti-secretory agents. A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line regimen. Bismuth-containing quadruple treatment, sequential treatment or a non-bismuth quadruple treatment (concomitant) are also an alternative therapy. Levofloxacin containing triple treatment are recommended as rescue treatment for infection of H. pylori after defeat of first-line therapy. The rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these remedies. Therefore, adding probiotic to the medications, developing anti-H. pylori photodynamic or phytomedicine therapy, and achieving a successful H. pylori vaccine may have the promising to present synergistic or additive consequence against H. pylori, because each of them exert different effects.

Medicinal plants in the treatment of Helicobacter pylori infections.

CONTEXT: Helicobacter pylori is a small, spiral, Gram-negative bacillus that plays a role in the pathogenesis of a number of diseases ranging from asymptomatic gastritis to gastric cancer. Schedule compliance, antibiotic drug resistance, and side-effects of triple or quadruple therapy have led to research for novel candidates from plants. OBJECTIVE: The purpose of this paper is to review the most potent medicinal plants of recently published literature with anti-H. pylori activity. For centuries, herbals have been used by traditional healers around the world to treat various gastrointestinal tract disorders such as dyspepsia, gastritis, and peptic ulcer disease. The mechanism of action by which these botanicals exert their therapeutic properties has not been completely and clearly elucidated. Anti-H. pylori properties may be one of the possible mechanisms by which gastroprotective herbs treat gastrointestinal tract disorders. MATERIALS AND METHODS: Electronic databases such as PubMed, Google scholar, EBSCO, and local databases were explored for medicinal plants with anti-H. pylori properties between 1984 and 2013 using key words "medicinal plants" and "Helicobacter pylori" or "anti-Helicobacter pylori". RESULTS: A total of 43 medicinal plant species belonging to 27 families including Amaryllidaceae, Anacardiaceae, Apiaceae, Apocynaceae, Asclepiadoideae, Asteraceae, Bignoniaceae, Clusiaceae, Chancapiedra, Combretaceae, Cyperaceae, Euphorbiaceae, Fabaceae, Geraniaceae, Lamiaceae, Lauraceae, Lythraceae, Menispermaceae, Myristicaceae, Myrtaceae, Oleaceae, Papaveraceae, Plumbaginaceae, Poaceae, Ranunculaceae, Rosaceae, and Theaceae were studied as herbs with potent anti-H. pylori effects. CONCLUSION: Traditional folk medicinal use of some of these plants to treat gastric infections is substantiated by the antibacterial activity of their extracts against H. pylori.

Curcumin-loaded guanidine functionalized PEGylated I3ad mesoporous silica nanoparticles KIT-6: practical strategy for the breast cancer therapy.

In this research, we have synthesized guanidine functionalized PEGylated mesoporous silica nanoparticles as a novel and efficient drug delivery system (DDS). For this purpose, guanidine functionalized PEGylated I3ad mesoporous silica nanoparticle KIT-6 [Gu@PEGylated KIT-6] was utilized as a promising system for the effective delivery of curcumin into the breast cancer cells. The modified mesoporous silica nanoparticles (MSNs) was fully characterized by different techniques such as transmission and scanning electron microscopy (TEM & SEM), N2 adsorption-desorption measurement, thermal gravimetric analysis (TGA), X-ray powder diffraction (XRD), and dynamic light scattering (DLS). The average particle size of [Gu@PEGylated KIT-6] and curcumin loaded [Gu@PEGylated KIT-6] nanoparticles were about 60 and 70 nm, respectively. This new system exhibited high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. It showed pH-responsive controlled characteristics and highly programmed release of curcumin leading to the satisfactory results in in vitro breast cancer therapy. Our results depicted that the pure nanoparticles have no cytotoxicity against human breast adenocarcinoma cells (MCF-7), mouse breast cancer cells (4T1), and human mammary epithelial cells (MCF10A).

Cytotoxic activity evaluation and QSAR study of chromene-based chalcones.

Chalcone and chromene motifs are synthetic or naturally occurring scaffolds with significant cytotoxic profile. Two types of novel regioisomeric chromene-chalcone hybrids, namely 1-(6-chloro or 6-methoxy-2H-chromen-3-yl)-3-phenylprop-2-en-1-one (Type A) and 3-(6-chloro or 6-methoxy-2H-chromen-3-yl)-1-phenylprop-2-en-1-one (Type B), both with different substituents on the phenyl ring attached to propenone linkage, have been evaluated for their cytotoxic activity against breast cancer cell lines (MCF-7 and MDA-MB-231). The results indicate that type A of chromene-chalcones demonstrated better cytotoxic profile than type B especially in MDA-MB-231 cell line. In addition, the growth inhibitory activity of most of the target compounds is higher than Etoposide as a reference drug. QSAR analysis of these novel compounds demonstrated that topological and geometrical parameters are among the important descriptors that influence the cytotoxic activity profile of compounds.

Anti-Helicobacter pylori activity of the methanolic extract of Geum iranicum and its main compounds.

Geum iranicum Khatamsaz, belonging to the Rosaceae family, is an endemic plant of Iran. The methanol extract of the roots of this plant showed significant activity against one of the clinical isolates of Helicobacter pylori which was resistant to metronidazole. The aim of this study was the isolation and evaluation of the major compounds of G. iranicum effective against H. pylori. The compounds were isolated using various chromatographic methods and identified by spectroscopic data (1H and 13C NMR, HMQC, HMBC, EI-MS). An antimicrobial susceptibility test was performed employing the disk diffusion method against clinical isolates of H. pylori and a micro dilution method against several Gram-positive and Gram-negative bacteria; additionally the inhibition zone diameters (IZD) and minimum inhibitory concentrations (MIC) values were recorded. Nine compounds were isolated: two triterpenoids, uvaol and niga-ichigoside F1, three sterols, beta-sitosterol, beta-sitosteryl acetate, and beta-sitosteryl linoleate, one phenyl propanoid, eugenol, one phenolic glycoside, gein, one flavanol, (+)-catechin, and sucrose. The aqueous fraction, obtained by partitioning the MeOH extract with water and chloroform, was the most effective fraction of the extract against all clinical isolates of H. pylori. Further investigation of the isolated compounds showed that eugenol was effective against H. pylori but gein, diglycosidic eugenol, did not exhibit any activity against H. pylori. The subfraction D4 was the effective fraction which contained tannins. It appeared that tannins were probably the active compounds responsible for the anti-H. pylori activity of G. iranicum. The aqueous fraction showed a moderate inhibitory activity against both Gram-positive and Gram-negative bacteria. The MIC values indicated that Gram-positive bacteria including Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus subtilis are more susceptible than Gram-neagative bacteria including Escherichia coli and Pseudomonas aeruginosa.

Antiproliferative activity of flavonoids: influence of the sequential methoxylation state of the flavonoid structure.

Dracocephalum kotschyi Boiss. has been used as part of an ethnobotanical remedy against many forms of human cancer in Iran. It has been demonstrated that a flavonoid named xanthomicrol from D. kotschyi contributes to its preferential antiproliferative activity against malignant cells. In the present study, the antiproliferative activity of its flavonoid fraction was further characterized. Using liquid-liquid extraction and a semi-preparative reversed-phase HPLC method, eight flavonoid aglycones were isolated from the aerial parts of the plant and their identities were confirmed through MS and NMR analyses as luteolin, naringenin, apigenin, isokaempferide, cirsimaritin, penduletin, xanthomicrol and calycopterin. The in vitro antiproliferative activity of each compound was evaluated against a panel of established normal and malignant cell lines using the MTT assay and some structure-activity relationships were observed. The hydroxyflavones (luteolin, apigenin and isokaempferide) exerted comparable antiproliferative activities against malignant and normal cells, while the methoxylated hydroxyflavones (cirsimaritin, penduletin, xanthomicrol and calycopterin) showed preferential activities against tumor cells. This activity may be of value in treating tumors as it would exert few side effects in normal tissues. Xanthomicrol selectively inhibited the growth of human gastric adenocarcinoma, while calycopterin selectively prevented human acute promyelocytic leukemia and human colon carcinoma cells proliferation.

3-imidazolyl-substituted flavans as potential antifungal agents: synthesis, stereochemical properties, and antifungal activity.

A new series of 3-imidazolyl-substituted flavan derivatives being equipped with a N-(phenethyl)-azole scaffold as the common pharmacophore of azole antifungals, were synthesized. The stereochemical and conformational properties of compounds were also characterized by (1)H-NMR data. The results of the antifungal evaluation of trans-3-imidazolyl-substituted flavan-4-ones and (Z)-trans-3-imidazolyl-substituted flavan-4-one oximes in comparison with the reference drug fluconazole indicated that most target compounds possessed significant in-vitro antifungal activities against the tested fungi, comparable or superior to fluconazole.

Antituberculosis agents X. Synthesis and evaluation of in vitro antituberculosis activity of 2-(5-nitro-2-furyl)- and 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,3,4-thiadiazole derivatives.

Two series of 2-(5-nitro-2-furyl)- and 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-5-propyl, allyl and propargyl)thio-1,3,4-thiadiazoles (6a-f) and 2-(5-nitro-2-furyl)- and 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-5-(nitrobenzyl)thio-1,3,4-thiadiazole derivatives (8a-f) have been synthesized and evaluated against Mycobacterium tuberculosis, as part of the TAACF TB screening program under direction of the US National Institute of Health, the NIAID division. Primary screening was conducted at a single concentration, 6.25 microg mL(-1), against M. tuberculosis H37Rv in BACTEC 12B medium, using the Microplate Alamar Blue Assay (MABA). The minimum inhibitory concentration (MIC) was determined for the compounds that demonstrated > or = 90% growth inhibition in the primary screening. A varying degree of antituberculosis activity (from 0-97% of growth inhibition) was observed with the alkylthio series (6a-f), and the nitroimidazole derivative with a propylthio group (6b) and the nitrofuran derivative with a propargylthio group (6e), were the most active compounds (MIC=3.13 and 1.56 microg mL(-1), respectively). Among the nitrobenzylthio derivatives (8a-f), all the ortho, meta and para nitrobenzyl isomers in the nitrofuran series exhibited good antituberculosis activity (MIC=3.13 microg mL(-1)), while the corresponding nitroimidazole analogues were completely inactive (Inhibition=0%).