Assessment of the Quality of Herbal Teas from Šabac, Serbia in Terms of the Content of Heavy Metals
Chemical components of teas have received great interest because they are related to health. In this work, data on the determination of foreign matter, loss on drying/water content, total ash and ash insoluble in hydrochloric acid are presented. The content of seven heavy metals including Cu, Fe, Mn, Zn, Ni, Cd and Pb were determined by atomic absorption spectrometry in samples of several herbal teas: and collected from Šabac's market, Serbia. The sample preparation procedure involved dry digestion and dissolution of the ash in 6M HCl and then in 0.1 M HNO. Herbal teas showed the concentration of heavy metals Cu, Fe, Mn, Zn and Ni in the range: 2.9 ± 0.1 - 22.2 ± 0.9 mg/kg, 118.5 ± 1.1 - 755.5 ± 2.5 mg/kg, 19.0 ± 5.8 - 561.0 ± 1.9 mg/kg, 6.5 ± 0.4 - 242.5 ± 1.4 mg/kg and 2.5 ± 0.1 - 10 ± 1.1 mg/kg, respectively. The level of copper in all samples was uniform. The highest content of Fe was in , while Mn and Zn were at maximum in . The levels of toxic heavy metals Cd and Pb were below the detection limit. The obtained values were compared with data available from literature. The herbal tea samples analyzed contained essential heavy metals (Cu, Fe, Mn, Zn) and probably essential in trace (Ni), and could obey the daily dietary requirements. Noncancer health risk assessment detected that the herbal teas of and can manifest some health risk to consumers.
Development of a Quantitative Determination Method for Aluminum Ions in Adsorbed Drugs Using Atomic Absorption Spectrometry with Electrothermal Atomization
A quantitative determination method for Al in immunobiological drugs using atomic absorption spectroscopy with electrothermal atomization was developed. Conditions for the preparation of aluminum hydroxide gel were selected [NaOH (5 M), heating in a boiling-water bath for 5 min followed by neutralization with conc. HNO]. The method was validated. The analytical range of Al was established in the interval 10 - 50 ig/L. The accuracy and in-laboratory precision were confirmed. The results allowed the proposed method to be considered an alternative for quantitative determination of Al in immunobiological drugs.
Glycoalkaloids of Plants in the Family Solanaceae (Nightshade) as Potential Drugs
Worldwide interest in medicinal plants and related drugs is growing because of the increased spectrum of new synthetic drugs. In this context, secondary plant metabolites are most significant. This review analyzes data on the structures and biosyntheses of metabolites such as glycoalkaloids; methods for their extraction from plants of the family Solanaceae, particularly potato ; their qualitative and quantitative analysis; biological activity; and toxicity. This information could be useful in the selection of methods for sample preparation and extraction of glycoalkaloids during the search for new plant sources with prospects of creating effective and safe pharmacological agents.
Synthesis of Glycyrrhizic Acid Conjugates with Amino-Acid Methyl Esters and their Ability to Stimulate Antibody Genesis in Mice
Conjugates of glycyrrhizic acid (GA) with methyl esters of -amino acids (valine, methionine, and glutamic acid) containing the amino-acid residues in the carbohydrate moiety of the glycoside were synthesized using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The resulting GA conjugates at a dose of 2 mg/kg stimulated a primary immune response (production of antibody-forming cells, AFCs) in outbred mice by 1.6 - 3 times as compared with the control. The conjugate of GA with Glu(OMe) stimulated antibody genesis in outbred mice 1.7 times more efficiently than -acetylmuramyl dipeptide and showed a stimulating effect on AFC production in the spleen of CBA mice.
Prospects of a Transdermal Dosage Form (Microneedles) and Justification of the Active Substance Selection for Development of a New Medicine
Prospects for the development of a transdermal dosage form (DF) based on microneedles were considered. Methods for obtaining such systems, the application areas, and data from the pharmaceutical market were examined. A wide sample of INNs that are used to reduce pain in osteoarthritis patients was formed based on clinical guidelines. The market capacity, sales by Anatomical Therapeutic Chemical (ATC-2) groups, and sales depending on the DF were discussed. Criteria for the choice of active ingredients with market potential were defined. An analysis of a short list revealed that meloxicam has sufficient market potential to create a microneedle DF. A forecast of meloxicam consumption based on time series models indicated stable sales-growth dynamics and a potential market size of 4.6 billion Russian rubles by 2030. Results of the study indicated good market prospects and justification of pharmaceutical development of a new transdermal DF including meloxicam microneedles as the active ingredient.
Synthesis, Characterization, and Antibacterial Activity of New Isatin Derivatives
1H-indol-2,3-dione (isatin) class of biologically active compounds have analgesic, anti-microbial, anti-inflammatory, anti-tubercular, anti-proliferative properties, and is also useful for the treatment of SARS-CoV. Schiff bases containing isatin moiety are known to have broad spectrum of biological activities like anti-viral, anti-tubercular, anti-fungal, and anti-bacterial. In this work, several Schiff base derivatives have been synthesized using two methods (synthetic and microwave) by reacting isatin with -phenylenediamine. The synthesized compounds were structurally characterized and their antimicrobial activity was tested against Gram-negative and Gram-positive bacteria using the inhibition zone method. Several newly synthesized isatin derivatives were found effective as antimicrobial agents and showed good potency (compounds , , , , ). Compound displayed higher antimicrobial activity than standard drug (Amoxicillin) against at higher concentration (16 μg/mL) and against at lower concentration (1 μg/mL).
Pharmacological Strategies for Overcoming Multidrug Resistance to Chemotherapy
Actual mechanisms of multidrug resistance (MDR) to chemotherapy in oncology are considered. ABC-transporters such as P-glycoprotein, BCRP protein, and MRP proteins take part in the development of resistance. The review presents the main classes of chemosensitizers, i.e., inhibitors of ABC transporters of the 1-4 generations. Plant polyphenols, i.e., flavonoids, are commonly referred to as the last (4) generation of MDR inhibitors. Chemosensitizers of different classes should be chosen with allowance for the patient mutation-expression profile and the receptor status of a particular tumor. The appropriate dosage of the chemosensitizer and the administration schedule can enhance the process of counteracting MDR.
Physicochemical Properties and Methods of Analysis of Vildagliptin (Review)
Vildagliptin is an oral agent which is a member of a new class of hypoglycemic drugs, dipeptidylpeptidase-4 (DPP-4) inhibitors. This review presents the physicochemical properties of vildagliptin and assesses analysis methods for its estimation in substances, medicinal formulations, and biological media. These are chromatographic, spectrophotometric, electrochemical and other analysis methods. The material presented may be useful for developing new methods for analysis of medicinal formulations containing vildagliptin. The most widely used method for assay of vildagliptin is HPLC.
New Analytical Methods for the Determination of New Anti-Viral Drug Favipiravir: A Potential Therapeutic Drug Against Covid-19 Virus, in Bulk and Dosage Forms
Simple, accurate and robust analytical methods have been developed and validated for the determination of favipiravir (FVPR) by RP-HPLC and UV spectroscopy techniques as per the ICH guidelines. In the RP-HPLC method for FVPR determination, the mobile phase was ammonium acetate buffer pH 6.5 in pump Aand methanol in pump B. The C18 (Sunfire) 5 μm, 4.6 × 250 mm column was used as a stationary phase, and the detection wavelength was at 323 nm. Under these conditions, FVPR was eluted as a sharp peak at 2.65 min and the overall time taken for each injection was 10 min. In case of the UV spectroscopy method, standard FVPR solutions were prepared with pure ethanol and scanned from 250 to 400 nm and a flourishing spectrum was obtained at 323 nm. Hence, the wavelength of 323 nm was fixed for the whole process of validation in both techniques. The limit of detection (LOD) and limit of quantification (LOQ) in the RP-HPLC method were 1.0 and 3.5 μg/mL, respectively, and the linearity was established in the 10 to 50 μg/mL range. In the UV spectroscopy method, the LOD and LOQ values were found to be 3.5 and 12 μg/mL, respectively, and the linearity was established within 20 to 60 μg/mL range. The regression coefficient was found to exceed 0.999 in both methods. The proposed RP-HPLC and UV spectroscopy techniques are simple, accurate, rugged and robust.
Comparative Analysis of Two Enoxaparin Sodium Drugs by Heptest
The optimal conditions for analysis of low-molecular-weight heparin (LMWH) drugs by the Heptest and the metrological characteristics of the Heptest method were determined. The effects of two LMWH preparations of enoxaparin sodium, the domestic drug Enoxaparin sodium (Technologiya Lekarstv, Russia) and the original drug Clexane (Sanofi, France), on the clotting time of human plasma in the Heptest were comparatively analyzed. The mean blood clotting times were calculated for each dilution of each series of Enoxaparin sodium and Clexane based on the results of the Heptest. Graphs of the dependence of the plasma clotting time on the degree of dilution of these drugs were plotted. The shapes of the curves of the dependence of the blood plasma clotting time on the activity of enoxaparin sodium were shown to be similar for both Enoxaparin sodium and Clexane. The Heptest method showed that Enoxaparin sodium (Technologiya Lekarstv, Russia) was comparable to the original drug Clexane (Sanofi, France).
Evaluation of Cellular Toxicity and Preclinical Safety of Using an Inhalable Liposomal form of Dexamethasone
A liposomal form of dexamethasone was obtained. Liposomal vesicles were formed. The efficiency of incorporating dexamethasone into the liposomes was 99.7%. The cytotoxicity of the obtained liposomes was studied on a culture of human lung fibroblast cells using the MTT assay. The toxicity of liposomal dexamethasone was less than that of dexamethasone solution after a 24-h incubation. The half-maximum inhibitory concentration (IC) was not achieved after 24 h when exposed to liposomal dexamethasone whereas IC was 27.5 mg/mL for lecithin (empty liposomes) and 177 µg/mL for dexamethasone solution. The toxicity of liposomal dexamethasone increased much more than that of dexamethasone solution after 48 h of incubation with IC values of 36 and 156 µg/mL, respectively. Thus, the liposomal form of dexamethasone has a latent period for implementation of the cytostatic (antiproliferative) action. Experiments on laboratory white rats of both sexes revealed that the inhalation use of liposomal dexamethasone insignificantly changed the functional parameters of their respiratory and cardiovascular systems. The study results could be used for conducting clinical trials.
Determination of Oseltamivir in Human Plasma by HPLC-MS/MS
A procedure for the determination of oseltamivir in human plasma by high-performance liquid chromatography( tandem mass spectrometry (HPLC-MS/MS) was proposed and validated. Arapid and easy-to-use method of liquid(liquid extraction with ethyl acetate using venlafaxine as an internal standard was used during sample preparation. The addition of benzoic acid to aqueous acetonitrile solutions of the analyte was shown to prevent its oxidative degradation. The detection limit and limit of quantitation were 0.08 and 0.30 ng/mL, respectively; the calibration range, 0.3-200 ng/mL ( = 0.9937); the total analysis time, 3.2 min. The within- and between-run accuracy ranged from 97 to 105%. The precision was <10%. The proposed procedure was characterized by selective determination of the analyte, the absence of significant matrix effects, the ability to dilute samples with high analyte concentrations, and satisfactory extraction recovery (≥89%). The analyte was stable when stored in plasma samples (4 h at room temperature, 31 d at (80°C, after three freeze(thaw cycles) and extracts under autosampler storage conditions (24 h at 15°C). The procedure was successfully used for oseltamivir quantitation in actual plasma samples from healthy volunteers obtained during a bioequivalence study of the new generic drug.
Strategy for the Choice of Disinfectants in Practical Medicine and Production
The problem of the strategy for choosing disinfectants in practical medicine is considered. The pandemic of the new coronavirus infection posed new problems for disinfectology. The expanded spectrum of disinfectants and antiseptics offered by the chemical industry in recent years requires justification for the choice in favor of any product. The goals and types of disinfection considered from current positions and the main groups of disinfectants used in Russia and their properties and spectra of activity are presented.
Viral Safety Issues in the Production and Manufacturing of Human Immunoglobulin Preparations from Equine Plasma/Serum
The current Russian and foreign pharmacopoeias either do not provide any information about existing types of viral diseases in horses or do not present it in full. Data of modern domestic and foreign literature was used to prepare the most complete list of viruses that cause equine diseases including 36 infectious agents, 25 of which are pathogenic for humans, 13 of the 25 of which are widespread throughout Russia. Information is provided on the magnitudes of the disease incubation periods (which are most often within one month), the external clinical signs of these diseases (which can also be asymptomatic), and the maximum possible concentrations of viruses in the blood of horses with these diseases (which can reach 8 log conventional units/mL of blood). This information is offered for use in critical production stages of heterologous immunoglobulin drugs for medical use to assure viral safety.
Ethionamide and Prothionamide Based Coumarinyl-Thiazole Derivatives: Synthesis, Antitubercular Activity, Toxicity Investigations and Molecular Docking Studies
The goal of this research work was to prepare and evaluate the antitubercular (anti-TB) activity of ethionamide (ETH) and prothionamide (PTH) based coumarinyl-thiazole derivatives. ETH and PTH were reacted with coumarin intermediates () to provide the target compounds ( and , respectively). Spectral studies confirmed the assigned structures of . The Microplate Alamar Blue Assay was utilized to evaluate the anti-TB activity of compounds against H37Rv strain in comparison to ETH, PTH, isoniazid (INH), and pyrazinamide (PYZ) as standard drugs. The cytotoxicity studies were carried out versus HepG2 and Vero cell lines. In addition. molecular docking studies of concerning the DprE1 enzyme and the evaluation of physicochemical and pharmacokinetic parameters were performed. Compounds and displayed equal minimum inhibitory concentration (MIC) values in comparison to INH (3.125 μg/ml) and PYZ (3.125 μg/ml), whereas and displayed better MIC values (1.562 μg/mL) than INH and PYZ. All compounds presented better anti-TB potential than ETH (6.25 μg/mL) and PTH (6.25 μg/mL). The studies of toxicity revealed that were safe up to 300 μg/mL concentration versus Vero and HepG2 cell lines. The molecular docking studies suggested that could possess anti-TB activity through the inhibition of the DprE1 enzyme. The studies showed that followed Lipinski's rule (drug-likeliness) and exhibited better gastrointestinal absorption than BTZ043 and macozinone. In conclusion, the ETH and PTH-based coumarinyl-thiazole template can help developing selective DprE1 enzyme inhibitors as potent anti-TB agents.
Ensuring Viral Safety of Equine Immunoglobulins during Production
Equine blood plasma/serum and intermediates must be monitored for the presence of live viruses pathogenic in humans during production of equine immunoglobulins. Information concerning low-cost and simple methods for the detection of live horse viruses pathogenic and non-pathogenic to humans was gained using data of modern domestic and foreign literature. These methods are based on cultivation of these viruses on sensitive biosystems. The presented information can be used to set up blood plasma/serum control of horses at different stages of immunoglobulin production, i.e., when taking blood from horses during their quarantine period, when collecting blood from immunized horses, and before bottling the medicinal intermediate in the primary package.
Drug Repurposing: a Shortcut to New Biological Entities
Drug repurposing has proved to be an efficient alternative to drug discovery owing to the facts that it is economical and risk factors being much lower or even negligible as the drug has already been approved for having safe use in humans. The contrast of drug discovery from drug repurposing, its advantages and the challenges faced during the process are the important factors to be considered in drug repurposing. The approaches in drug discovery include three methods namely computational, biological and mixed. Moreover, the recent advancement in application of drugs for COVID-19 proved drug repurposing is a vital strategy in medical science for the upcoming years.
Bioavailability and Safety of Dihydroquercetin (Review)
Dihydroquercetin (DHQ) is a bioflavonoid with high antioxidant, capillary-protective, and anti-inflammatory activity. DHQ has previously been used for treating Middle East respiratory syndrome coronavirus (MERS-CoV) infection and is currently considered a potential regulator of oxidative stress as part of COVID-19 multipurpose therapy. DHQ has a high safety profile but low bioavailability that limits its use. Innovative techniques (liposomization, crystal engineering, etc.) can be used to increase its bioavailability.
Synthesis and Anti-Inflammatory Activity Evaluation of Some Benzimidazole Derivatives
Hyper-inflammation aggravates the symptoms of both communicable and non-communicable diseases. Therefore, anti-inflammatory compounds may have wide therapeutic application. Benzimidazole is a privileged scaffold and its success in drug development is evident from the long list of benzimidazole-based drugs with wide range of applications. This study was undertaken to develop new small molecules with anti-inflammatory properties. Compounds MBPHYD, MBNHYD and MBHYDX were synthesised, purified, characterised and found to be non-toxic both (in 100 μMconcentration for 24 h vs. 3000 Vero cells/well) and (at a dose of 100 mg/kg in female Wistar rats with animals observed for 48 h for any mortality). Compounds MBPHYD and MBNHYD were found to possess significant anti-inflammatory properties. Further, analysis suggested their compliance with drug-likeness. While no toxicity was predicted, both compounds were suggested to have good oral bioavailability. Thus, results of this study may encourage further investigation to establish new anti-inflammatory benzimidazoles for application against various disease conditions.
Determination of Hydroxychloroquine by Cathodic Electrochemiluminescence
Cathodic electrochemiluminescence (CECL) of hydroxychloroquine (HCQ) in aqueous solutions on an aluminum electrode is described. The analytical possibilities of the phenomenon are evaluated. The conditions for HCQ determination in slightly alkaline and acidic solutions are optimized. The possibility of analysis in the concentration range 0.1 - 300 mg/L is shown. CECL can be a supplement to well-known methods of HCQ determination in pharmaceuticals by a method based on a new type of luminescent response signal.
: A Review on the Phytochemical and Pharmacological Aspects
J.F. Gmel. (family: Sapotaceae), commonly known as Mahua in Indian dialects, occupies the importance as one of the fuel-efficient, energy-saving plant species. Extensive studies showed that the presence of phytochemicals e.g., carbohydrates, fatty acids, flavonoids, saponins, steroids, triterpenoids and glycosidic compounds in the extract of this species. Pharmacologically, it has been used against various disorders in indigenous system of medicine, inckuding antioxidant, anti-inflammatory, anticancer, hepatoprotective, anti-diabetic and wound healing activities. This review highlights various pharmacological activities, phytochemistry and importance of plant for medicine.