A highly selective Hg2+ colorimetric sensor and antimicrobial agent based on green synthesized silver nanoparticles using Equisetum diffusum extract.

Plasmonic nanoparticles such as Ag have gained great interest in the biomedical domain and chemical analysis due to their unique optical properties. Herein, we report a simple, cost-effective, and highly selective colorimetric sensor of mercury(ii) based on E. diffusum (horsetail) extract-functionalized Ag nanoparticles (ED-AgNPs). The ED-AgNPs were synthesized by exploiting the coordination of Ag+ with the various functional groups of ED extract under sunlight exposure for only tens of seconds. ED-AgNPs (63 nm) were characterized using various techniques such as UV-vis, FTIR, DLS, SEM and EDX. FTIR spectra suggested the successful encapsulation of the AgNPs surface with ED extract and XRD confirmed its crystalline nature. This ED-AgNPs colorimetric sensor revealed remarkable selectivity towards Hg2+ in aqueous solution among other transition metal ions through a redox reaction mechanism. Besides, the sensor exhibited high sensitivity with rapid response and a detection limit of 70 nM. The sensor demonstrated feasibility for Hg(ii) detection in spiked tap and river water samples. In addition, the synthesized ED-AgNPs revealed enhanced antimicrobial activity with higher efficacy against the Gram-positive bacterium (L. monocytogenes with an inhibition zone of 18 mm) than the Gram-negative bacterium (E. coli with an inhibition zone of 10 mm). The simplicity and adaptability of this colorimetric sensor render it a promising candidate for on-site and point-of-care detection of heavy metal ions in diverse conditions.

Improved Photocatalytic and Antioxidant Activity of Olive Fruit Extract-Mediated ZnO Nanoparticles.

Photodegradation is an efficient strategy for the removal of organic pollutants from wastewater. Due to their distinct properties and extensive applications, semiconductor nanoparticles have emerged as promising photocatalysts. In this work, olive (Olea Europeae) fruit extract-based zinc oxide nanoparticles (ZnO@OFE NPs) were successfully biosynthesized using a one-pot sustainable method. The prepared ZnO NPs were systematically characterized using UV-Vis, FTIR, SEM, EDX and XRD and their photocatalytic and antioxidant activity was evaluated. SEM demonstrated the formation of spheroidal nanostructures (57 nm) of ZnO@OFE and the EDX analysis confirmed its composition. FTIR suggested the modification/capping of the NPs with functional groups of phytochemicals from the extract. The sharp XRD reflections revealed the crystalline nature of the pure ZnO NPs with the most stable hexagonal wurtzite phase. The photocatalytic activity of the synthesized catalysts was evaluated by measuring the degradation of methylene blue (MB) and methyl orange (MO) dyes under sunlight irradiation. Improved degradation efficiencies of 75% and 87% were achieved within only 180 min with photodegradation rate constant k of 0.008 and 0.013 min-1 for MB and MO, respectively. The mechanism of degradation was proposed. Additionally, ZnO@OFE NPs exhibited potent antioxidant activity against DPPH, hydroxyl, peroxide and superoxide radicals. Hence, ZnO@OFE NPs may have potential as a cost-effective and green photocatalyst for wastewater treatment.

Study of influence of Catha edulis (Khat) chewing on oral pharmacokinetics of irbesartan in rats using a newly developed HPLC-UV method.

Khat consumers might use a number of drugs for underlying conditions; however the potential drug-herb interaction between khat and other drugs including Irbesartan (IRB) is unknown. The present study was conducted to evaluate the effects of khat chewing on pharmacokinetic profile of IRB, a commonly available antihypertensive agent. The pharmacokinetic profile of orally administered IRB (15.5 mg/kg) with and without pre-administration of khat (12.4 mg/kg) were determined in Sprague-Dawley rats. IRB was estimated in rat plasma samples using a newly developed HPLC method. The chromatographic separation of the drug and internal standard (IS) was performed on a C-18 column (Raptor C-18, 100 mm × 4.6 mm id.; 5 µm) using a mobile phase consisting of 10 mM ammonium acetate buffer (pH 4.0) and acetonitrile in a ratio 60:40 v/v. Acceptable linearity for IRB was recorded at 1 - 12 µg/mL concentration range (R2 > 0.99). Intra-day and inter-day precision (%RSD = 0.44% - 3.27% and 0.39-1.98% respectively) and accuracy (% recovery = 98.3 - 104.3%) in rat plasma was within the acceptable limit according to USFDA guidelines. The AUC0-t was found to be significantly increased in IRB-khat co-administered rats as compared to rats receiving IRB only; whereas, the Tmax (0.5 h) value remained unchanged. Results of this study revealed that the IRB level considerably increased in rat plasma upon co-administration of khat. This might be due to the inhibition of CYP2D9 by khat which is the principal cytochrome P450 isoform responsible for IRB metabolism.

Protective effects of apigenin on methylmercury-induced behavioral/neurochemical abnormalities and neurotoxicity in rats.

Methylmercury (MeHg) is a neurotoxin that induces neurotoxicity and cell death in neurons. MeHg increases oligodendrocyte death, glial cell activation, and motor neuron demyelination in the motor cortex and spinal cord. As a result, MeHg plays an important role in developing neurocomplications similar to amyotrophic lateral sclerosis (ALS). Recent research has implicated c-JNK and p38MAPK overactivation in the pathogenesis of ALS. Apigenin (APG) is a flavonoid having anti-inflammatory, antioxidant, and c-JNK/p38MAPK inhibitory activities. The purpose of this study is to determine whether APG possesses neuroprotective effects in MeHg-induced neurotoxicity in adult rats associated with ALS-like neuropathological alterations. In the current study, the neurotoxin MeHg causes an ALS-like phenotype in Wistar rats after 21 days of oral administration at a dose of 5 mg/kg. Prolonged administration of APG (40 and 80 mg/kg) improved neurobehavioral parameters such as learning memory, cognition, motor coordination, and grip strength. This is mainly associated with the downregulation of c-JNK and p38MAPK signaling as well as the restoration of myelin basic protein within the brain. Furthermore, APG inhibited neuronal apoptotic markers (Bax, Bcl-2, and caspase-3), restored neurotransmitter imbalance, decreased inflammatory markers (TNF- and IL-1), and alleviated oxidative damage. As a result, the current study shows that APG has neuroprotective potential as a c-JNK and p38MAPK signaling inhibitor against MeHg-induced neurotoxicity in adult rats. Based on these promising findings, we suggested that APG could be a potential new therapeutic approach over other conventional therapeutic approaches for MeHg-induced neurotoxicity in neurobehavioral, molecular, and neurochemical abnormalities.

Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents.

Natural products represents an important source of new lead compounds in drug discovery research. Several drugs currently used as therapeutic agents have been developed from natural sources; plant sources are specifically important. In the past few decades, pharmaceutical companies demonstrated insignificant attention towards natural product drug discovery, mainly due to its intrinsic complexity. Recently, technological advancements greatly helped to address the challenges and resulted in the revived scientific interest in drug discovery from natural sources. This review provides a comprehensive overview of various approaches used in the selection, authentication, extraction/isolation, biological screening, and analogue development through the application of modern drug-development principles of plant-based natural products. Main focus is given to the bioactivity-guided fractionation approach along with associated challenges and major advancements. A brief outline of historical development in natural product drug discovery and a snapshot of the prominent natural drugs developed in the last few decades are also presented. The researcher's opinions indicated that an integrated interdisciplinary approach utilizing technological advances is necessary for the successful development of natural products. These involve the application of efficient selection method, well-designed extraction/isolation procedure, advanced structure elucidation techniques, and bioassays with a high-throughput capacity to establish druggability and patentability of phyto-compounds. A number of modern approaches including molecular modeling, virtual screening, natural product library, and database mining are being used for improving natural product drug discovery research. Renewed scientific interest and recent research trends in natural product drug discovery clearly indicated that natural products will play important role in the future development of new therapeutic drugs and it is also anticipated that efficient application of new approaches will further improve the drug discovery campaign.

Sulforaphane: A review of its therapeutic potentials, advances in its nanodelivery, recent patents, and clinical trials.

Traditionally, herbal supplements have shown an exceptional potential of desirability for the prevention of diseases and their treatment. Sulforaphane (SFN), an organosulfur compound belongs to the isothiocyanate (ITC) group and is mainly found naturally in cruciferous vegetables. Several studies have now revealed that SFN possesses broad spectrum of activities and has shown extraordinary potential as antioxidant, antitumor, anti-angiogenic, and anti-inflammatory agent. In addition, SFN is proven to be less toxic, non-oxidizable, and its administration to individuals is well tolerated, making it an effective natural dietary supplement for clinical trials. SFN has shown its ability to be a promising future drug molecule for the management of various diseases mainly due to its potent antioxidant properties. In recent times, several newer drug delivery systems were designed and developed for this potential molecule in order to enhance its bioavailability, stability, and to reduce its side effects. This review focuses to cover numerous data supporting the wide range of pharmacological activities of SFN, its drug-related issues, and approaches to improve its physicochemical and biological properties, including solubility, stability, and bioavailability. Recent patents and the ongoing clinical trials on SFN are also summarized.

Medicinal Plants and Isolated Molecules Demonstrating Immunomodulation Activity as Potential Alternative Therapies for Viral Diseases Including COVID-19.

Plants have been extensively studied since ancient times and numerous important chemical constituents with tremendous therapeutic potential are identified. Attacks of microorganisms including viruses and bacteria can be counteracted with an efficient immune system and therefore, stimulation of body's defense mechanism against infections has been proven to be an effective approach. Polysaccharides, terpenoids, flavonoids, alkaloids, glycosides, and lactones are the important phytochemicals, reported to be primarily responsible for immunomodulation activity of the plants. These phytochemicals may act as lead molecules for the development of safe and effective immunomodulators as potential remedies for the prevention and cure of viral diseases. Natural products are known to primarily modulate the immune system in nonspecific ways. A number of plant-based principles have been identified and isolated with potential immunomodulation activity which justify their use in traditional folklore medicine and can form the basis of further specified research. The aim of the current review is to describe and highlight the immunomodulation potential of certain plants along with their bioactive chemical constituents. Relevant literatures of recent years were searched from commonly employed scientific databases on the basis of their ethnopharmacological use. Most of the plants displaying considerable immunomodulation activity are summarized along with their possible mechanisms. These discussions shall hopefully elicit the attention of researchers and encourage further studies on these plant-based immunomodulation products as potential therapy for the management of infectious diseases, including viral ones such as COVID-19.

Nanoparticles of resveratrol attenuates oxidative stress and inflammation after ischemic stroke in rats.

Resveratrol is a nutraceutical compound that has exciting pharmacological potential in different diseases, including stroke. Due to its low bioavailability, the efficacy of resveratrol is minimal. Hence, the present study is aimed to synthesize and characterize nanoparticles of resveratrol (NR) followed by evaluating the neuroprotective role and elucidate the mechanism of NR in a rat model of middle cerebral artery occlusion (MCAO). Male Wistar rats (280-300 g) were pretreated with various doses (125 µg, 250 µg, and NR 500 µg; once daily, i.p.) of NR or vehicle (nanostructured lipid carriers) for 10 days. MCAO was performed for 2 h followed by reperfusion of 22 h. After 24 h of MCAO, animals were tested for the neurological outcome and were sacrificed for the analysis of infarct volume, oxidative, inflammatory, and apoptotic markers. NR-treated rats showed a substantial reduction in infarction compared to saline controls in parallel with improved motor and cognitive function. Further, NR pretreatment ameliorated oxidative stress markers and attenuated activities of antioxidant enzymes and Na+ K+ ATPase. The enhanced activities of caspases -3 and -9 and cytokines: interleukin-1ß, and -6, and tumor necrosis factor-ɑ) in the MCAO group were significantly protected with the treatment of 500 µg of NR. Taken together, these data indicate that inhibition by NR has therapeutic potential in the ischemic stroke model. Further investigations into the therapeutic efficacy and post-treatment protocols are needed to confirm whether NR treatment could be a promising candidate for a stroke.

Spectroscopic characterization of the interactions of bovine serum albumin with medicinally important metal ions: platinum (IV), iridium (III) and iron (II).

Serum albumin protein plays a key role in the transportation and distribution of bioactive species including metal ions and metal-based drugs and, therefore, the nature of their binding could provide important insight for the development of new drugs. In the present investigation, binding interactions of bovine serum albumin (BSA) with three biologically important metal ions: Pt4+, Ir3+ and Fe2+ were screened using easy-to-use and cost-effective Fourier-Transform Infrared (FT-IR) and Ultraviolet-Visible (UV-Vis) spectroscopic techniques. Prior to the screening, the protein and metal ions were allowed to interact at physiological pH (7.4) and the spectral changes were monitored upon interaction. In FT-IR spectrum, the position of amide I band (C=O stretching) was shifted from 1652 cm-1 in case of free BSA to 1659, 1657 and 1656 cm-1 in BSA-Pt4+, BSA-Ir3+ and BSA-Fe2+ complexes, respectively. This spectral shifting was due to the binding of metal ions to N and O atoms of BSA peptide bonds. The interaction was further demonstrated by a remarkable reduction in spectral intensities of amide I and II bands. Secondary protein structure analysis revealed conformational changes characterized by a substantial decrease in α-helix (11.29-27.41%) accompanied by an increase in ß-sheet and ß-antiparallel contents. The absorption of BSA at a constant concentration at 280 nm was successively reduced as the concentration of Pt4+ and Ir3+ ions increased. On the other hand, the absorption of BSA-Fe2+ complex successively increased with the increase in the concentration of Fe2+ in the test solution. The binding constants for BSA-Pt4+, BSA-Ir3+ and BSA-Fe2+ complexes were calculated to be 1.55×104, 5.67×104 and 3.78×104 M-1, respectively. The results revealed that the three metal ions showed binding affinities with the BSA protein in the order: Ir3+>Fe2+>Pt4+.

Bioactive Natural Antivirals: An Updated Review of the Available Plants and Isolated Molecules.

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.

Recent Advancements in the Diagnosis, Prevention, and Prospective Drug Therapy of COVID-19.

Severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2), previously called 2019 novel CoV, emerged from China in late December 2019. This virus causes CoV disease-19 (COVID-19), which has been proven a global pandemic leading to a major outbreak. As of June 19, 2020, the data from the World Health Organization (WHO) showed more than 8.7 million confirmed cases in over 200 countries/regions. The WHO has declared COVID-19 as the sixth public health emergency of international concern on January 30, 2020. CoVs cause illnesses that range in severity from the common cold to severe respiratory illnesses and death. Nevertheless, with technological advances and imperative lessons gained from prior outbreaks, humankind is better outfitted to deal with the latest emerging group of CoVs. Studies on the development of in vitro diagnostic tests, vaccines, and drug re-purposing are being carried out in this field. Currently, no approved treatment is available for SARS-CoV-2 given the lack of evidence. The results from preliminary clinical trials have been mixed as far as improvement in the clinical condition and reduction in the duration of treatment are concerned. A number of new clinical trials are currently in progress to test the efficacy and safety of various approved drugs. This review focuses on recent advancements in the field of development of diagnostic tests, vaccines, and treatment approaches for COVID-19.

The Spectrum of Thiazolidinediones against Respiratory Tract Pathogenic Bacteria: An In Vitro and In Silico Approach.

BACKGROUND AND OBJECTIVES: Drug design strategies to develop novel broad-spectrum antibacterial agents for the treatment of respiratory tract infections that can combat bacterial resistance are currently gaining momentum. 2,4-thiazolidinedione is a structural scaffold that contains pharmacophores similar to ß-lactam and non- ß-lactam antibiotics. The objective of the study was to synthesize newer 3,5-Disubstituted-2,4-Thiazolidinediones (DTZDs) and subject them to in vitro antibacterial screening against bacterial pathogens. Also, we performed in silico docking of selected compounds to penicillin-binding proteins and beta-lactamases. METHODS: Intermediate Schiff bases were prepared by the reaction between 2,4-thiazolidinedione and an appropriate aldehyde followed by acylation of the ring nitrogen with 3-brompropanoyl chloride resulting in DTZDs. Minimum inhibitory concentrations were determined against few bacteria infecting the respiratory tract by the broth tube dilution method. Zones of inhibitions against the bacteria were also determined using agar well diffusion technique. Molecular docking of the compounds to all types of Penicillin-Binding Proteins (PBPs) and ß-lactamases was also carried out. RESULTS: Compounds DTZD12 and DTZD16 exhibited broad-spectrum antibacterial activity. The minimum inhibitory concentrations of the compounds were 175µg/100µL. Measurements of the zones of inhibitions indicated that compound DTZD12 was more active than DZTD16. E. coli was the most susceptible organism. Docking results established that both the compounds were able to interact with PBPs and ß-lactamases through strong hydrogen bonds, especially the unique interaction with active serine residue of the PBP for inhibition of cell wall synthesis. CONCLUSION: DTZD12 and DTZD16 can be developed into antibacterial drugs for respiratory tract infections to oppose bacterial resistance, or can also be used as leads for repurposing the existing 2,4- thiazolidinediones.

Analysis of amphetamine and methamphetamine contents in seized tablets from Jazan, Saudi Arabia by liquid chromatography-mass spectroscopy (LC-MS/MS) and chemometric techniques.

A number of illegal amphetamine tablets were seized from three different cities of Jazan province of southern Saudi Arabia and were analyzed for amphetamine and methamphetamine contents using LC-MS/MS technique. Analyses were performed using a previously reported method taking 0.1 M ammonium formate buffer (85%) and 15% acetonitrile with 0.1% formic acid as mobile phase with a total runtime of 12 min. This method was successfully applied for the routine analysis of amphetamine and methamphetamine in the seized tablets using amphetamine-D5 and methamphetamine-D5 as internal standards. Hierarchical cluster analysis was performed to establish the similarity between samples. The retention times (RT) for internal standard, amphetamine and methamphetamine were observed to be within 6.0-7.1 min. Ten tablet samples from each city were subjected to analysis and the amount of amphetamine in all the samples were found to be in the range of 9.07-14.77 mg, whereas, the amount of methamphetamine ranged from 0.12 to 0.24 mg in each tablet. Hierarchical cluster analysis showed presence of five clusters of samples indicating different characteristics and possible sources of amphetamine tablets. The largest cluster consisted of 15 samples which are expected to be of the same origin. Both amphetamine and methamphetamine are considered to be illegal products and their illegal trade and use is banned in many countries including Saudi Arabia. Therefore, there is an urgent need of strict regulations worldwide to check the illicit trafficking of these psychoactive substances and should be considered on priority.

Pharmacological melioration by Selenium on the toxicity of tellurium in neuroendocrine centre (Pituitary Gland) in male wistar rats: A mechanistic approach.

PURPOSE: The present research was designed to evaluate the toxicity of tellurium and its prevention by selenium on the pituitary gland in male Wistar rats. METHODS: 30 rats were used weighing 200-250 gm, and randomly divided them into five groups. Each group contained an equal number of animals. Group-1 was nominated as control group. Group-2 received an intraperitoneal dose of selenium 0.3  mg per kg body wt. Group-3 was administered with tellurium 4.15 mg per kg body wt. Group-4 was given low-dose (L) of both selenium 0.15 and tellurium 2.075, Group-5 was given High-dose (H) of both selenium 0.3 and tellurium 4.15 mg/kg body wt. orally once in a day. After 15 days of dosing, the behavioral activities- motor co-ordination rotarod and grip strength test were measured. On 16th-day animals were sacrificed and activity of LPO, GSH, caspase-3, caspase-9, GPx, GR, SOD, catalase, and AChE were performed on the pituitary gland as per standard method reported. RESULTS: Se when given together with Te, significantly protects the motor coordination up to 32.5%, and also protects the grip strength up to 75% in group 4 and 5 respectively as compared to group- 3. Se + Te treatment protects the activity of TBARS up to 48.68% and GSH is 58%. As compared to control, it protects caspase-3 up to 118% and caspase-9 up to 83%. The level of AChE was also observed to be modulated by the administration of Se in Group- 4 and 5. Se + Te protected AChE up to 28.6%. Similar findings were observed for the biochemical activities of GPx (140% protection), SOD (458%), GR (159%), and catalase (95%) activities that were protected significantly Se + Te in Group- 4 and 5. CONCLUSION: Selenium dose-dependently protects behavioral activities. It also protects apoptosis, oxidative stress, and AChE activities in the pituitary gland.

In vivo assessment of genotoxic potential of brown shammah (smokeless tobacco) in bone marrow cells of mice.

This study was aimed to assess the genotoxicity of brown shammah (BS), a local form of smokeless tobacco, popular in Middle East countries including Yemen, Saudi Arabia and Sudan. The genotoxicity was explored using in vivo chromosomal aberration (CA), micronucleus (MN) and sperm abnormality (SA) assays. In addition, oxidative stress was also determined using various hepatic markers. Swiss albino mice were selected for the study, which were divided in to 5 groups of six animals each. They include, negative control (NC, received only vehicle) as well as positive control group (PC, received vehicle for 2 weeks followed by administration of cyclophosphamide, CP). Depending upon their dose, three BS treated animal groups were BS-100, 300 and 900 mg/kg. Doses of BS were obtained by suspending BS in 0.5% CMC (carboxy methyl cellulose) and orally administered once a day for 2 weeks. Significant augmentation of the average percentage of aberrant metaphase (AM), CA per cells and suppressed mitotic activity was observed on post administration of BS. In addition, BS increased the occurrence of MNPCEs (micronucleated polychromatic erythrocytes) formation, induced cytotoxicity and increased percentage of abnormal sperms as compared to NC. Moreover, BS also induced oxidative stress as the activities of hepatic superoxide dismutase (SOD) and glutathione (GSH) were reduced and malondialdehyde (MDA) content were increased by BS. Cyclophosphamide was utilized as clastogen, showed anticipated positive results and confirmed the sensitivity of test system. Therefore, it may be deduced from the study that the BS possesses genotoxic effects on mice bone marrow and germ cells in vivo.

Gefitinib loaded nanostructured lipid carriers: characterization, evaluation and anti-human colon cancer activity in vitro.

NLC containing Gefitinib (NANOGEF) was prepared using stearic acid, sesame oil and surfactants (sodium lauryl sulfate and tween 80). NANOGEFs were evaluated for particle size, polydispersity index (PdI), zeta potential, entrapment efficiency (EE), stability, release studies and cytotoxicity studies (MTT assay). The optimized NANOGEF exhibited particle size of 74.06 ± 9.73 d.nm, PdI of 0.339 ± 0.029 and EE of 99.76 ± 0.015%. The TEM study revealed spherical shape of NANOGEF formulations. The slow and sustained release behavior was exhibited by all NANOGEFs. The effects of surfactants were observed not only on particle size but also on zeta potential, entrapment efficiency, stability and release studies. The MTT assay revealed 4.5 times increase in cytotoxicity for optimized NANOGEF (IC50 = 4.642 µM) when compared with Gefitinib alone (IC50 = 20.88 µM in HCT-116 cells). Thus NANOGEF may be considered as a potential drug delivery system for the cure of colon cancer.

Risk-based exposure assessment for multiple toxic elements encountered by children in school playgrounds and parks in the southwest region of Saudi Arabia.

Children are in direct contact with surface soil and may inadvertently ingest and inhale toxic contaminants while playing; hence, special attention should be given to playgrounds regarding toxic contaminants. The concentrations of ten toxic metals were determined in soil samples collected from school playgrounds and children's parks from the southwest region of Saudi Arabia. The soils were moderately alkaline (pH 7.6-8.8), the texture was dominated by sand particles (54-88%), and the organic matter was in the range of 2.06 to 4.82%. Analytical solutions were prepared by microwave-digestion using a HNO3/H2O2 mixture, and the concentrations of toxic elements were measured by inductively coupled plasma mass spectrometry (ICP-MS). Metal concentrations were recorded in the range of 0.014-0.087, 1.14-3.54, 0.85-23.29, 0.77-36.32, 312.6-2065.7, 285.3-822.6, 75.4-240.8, 0.00-53.12, 0.52-6.80, and 1.25-92.12 mg/kg dry soil for Cd, Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, and Zn, respectively. The levels of heavy metals in the studied playgrounds were below the permissible limits, indicating insignificant influence of anthropogenic activities and can be considered as unpolluted soil. Values of the enrichment coefficient (EC) and contamination factor (CF) were found to be less than one, suggesting that the source of these elements is mainly the local soil, with the exception of Ni and Zn in certain playgrounds (CF > 1), which indicates a possible contamination from external sources. The non-carcinogenic hazard index calculated for all of the metals was below one, indicating that the exposure to heavy metal through playground soil is unlikely to produce any adverse health effect in children playing in the playgrounds.

Critical Insight into the Design of PPAR-γ Agonists by Virtual Screening Techniques.

BACKGROUND: Design of novel PPAR-γ modulators with better binding efficiency and fewer side effects to treat type 2 diabetes is still a challenge for medicinal chemists. Cost and time efficient computational methods have presently become an integral part of research in nuclear receptors and their ligands, enabling hit to lead identification and lead optimization. This review will focus on cutting-edge technologies used in most recent studies on the design of PPAR- γ agonists and will discuss the chemistry of few molecules which emerged successful. METHODS: Literature review was carried out in google scholar using customized search from 2011- 2017. Computer-aided design methods presented in this article were used as search terms to retrieve corresponding literature. RESULTS: Virtual screening of natural product libraries is an effective strategy to harness nature as the source of ligands for PPARs. Rigid and induced fit docking and core hopping approach in docking are rapid screening methods to predict the PPAR- γ and PPAR-α/ γ dual agonistic activity. Onedimensional drug profile matching is one of the recent virtual screening methods by which an antiprotozoal drug, Nitazoxanide was identified as a PPAR- γ agonist. CONCLUSION: It is concluded that to achieve a convincing and reliable design of PPAR-γ agonist by virtual screening techniques, customized workflow comprising of appropriate models is essential in which methods may be applied either sequentially or simultaneously.

A Fast and Validated Reversed-Phase HPLC Method for Simultaneous Determination of Simvastatin, Atorvastatin, Telmisartan and Irbesartan in Bulk Drugs and Tablet Formulations.

The aim of this study was to develop and validate a fast and simple reversed-phase HPLC method for simultaneous determination of four cardiovascular agents-atorvastatin, simvastatin, telmisartan and irbesartan in bulk drugs and tablet oral dosage forms. The chromatographic separation was accomplished by using Symmetry C18 column (75 mm × 4.6 mm; 3.5 µ) with a mobile phase consisting of ammonium acetate buffer (10 mM; pH 4.0) and acetonitrile in a ratio 40:60 v/v. Flow rate was maintained at 1 mL/min up to 3.5 min, and then suddenly changed to 2 mL/min till the end of the run (7.5 min). The data was acquired using ultraviolet detector monitored at 220 nm. The method was validated for linearity, precision, accuracy and specificity. The developed method has shown excellent linearity (R² > 0.999) over the concentration range of 1-16 µg/mL. The limits of detection (LODs) and limits of quantification (LOQs) were in the range of 0.189-0.190 and 0.603-0.630 µg/mL, respectively. Inter-day and intra-day accuracy and precision data were recorded in the acceptable limits. The new method has successfully been applied for quantification of all four drugs in their tablet dosage forms with percent recovery within 100 ± 2%.

Targeting Peroxisome Proliferator-Activated Receptors Using Thiazolidinediones: Strategy for Design of Novel Antidiabetic Drugs.

Thiazolidinediones are a class of well-established antidiabetic drugs, also named as glitazones. Thiazolidinedione structure has been an important structural domain of research, involving design and development of new drugs for the treatment of type 2 diabetes. Extensive research on the mechanism of action and the structural requirements has revealed that the intended antidiabetic activity in type 2 diabetes is due to their agonistic effect on peroxisome proliferator-activated receptor (PPAR) belonging to the nuclear receptor super family. Glitazones have specific affinity to PPARγ, one of the subtypes of PPARs. Certain compounds under development have dual PPARα/γ agonistic activity which might be beneficial in obesity and diabetic cardiomyopathy. Interesting array of hybrid compounds of thiazolidinedione PPARγ agonists exhibited therapeutic potential beyond antidiabetic activity. Pharmacology and chemistry of thiazolidinediones as PPARγ agonists and the potential of newer analogues as dual agonists of PPARs and other emerging targets for the therapy of type 2 diabetes are presented. This review highlights the possible modifications of the structural components in the general frame work of thiazolidinediones with respect to their binding efficacy, potency, and selectivity which would guide the future research in design of novel thiazolidinedione derivatives for the management of type 2 diabetes.