In-silico screening of phytomolecules against multiple targets for wound management.

Chronic wound healing, especially in burns, is a major medical challenge with limited treatments. This study employs computational tools to identify phytomolecules that target multiple pathways involved in wound healing. By utilizing shape analysis, molecular docking, and binding energy calculations, potential compounds are pinpointed,to address the growing problem of chronic wounds. Initially, a set of phytomolecules from the ZINC database of natural molecules was screened to find compounds with shapes similar to well-known wound healing phytomolecules like curcumin, chromogenic acid, gallic acid, and quercetin. The most promising phytomolecules identified through shape similarity were further studied through molecular docking studies on several key targets involved in wound healing, including TNF-α, FGF, and TGF-ß. Among the tested phytomolecules, a ligand known as Fluorophenyl(5-(5-chloro-1-(2-fluorophenyl)-2-oxopentyl)-4,5,6,7-tetrahydrothieno[3,2c]pyridine-2-yl acetate) exhibited a strong affinity with favourable binding interactions for TNF-α ( - 7.1 kcal/mole), FGF (-6.9 kcal/mole), and TGF-ß (-5.1 kcal/mole). Another compound, 2,4 methoxybenzylidene-(-3)-oxo-2,3-dihydro-1-benzofuran-6-yl-4-methoxybenzoate, demonstrated a strong affinity with low binding energy for TNF-α ( - 6.8 kcal/mole) and FGF ( - 7.0 kcal/mole) targets. Isosakuranetin and Ermanin displayed moderate affinity for both TNF-α and FGF, with the highest affinity observed for the TGF-ß target. These findings suggest that these identified phytomolecules hold promise as potential lead compounds for further structural modifications, with the goal of designing new molecules that can target multiple pathways involved in the wound healing process.

Decalepis hamiltonii root fraction alleviates CCl4 hepatotoxicity in a rat model.

BACKGROUND: Decalepis hamiltonii (D. hamiltonii) is Indian folk medicine in herbal preparations, to reduce appetite, and cures dysentery, bronchitis, uterine hemorrhage, and other ailments. OBJECTIVE: The current investigation focused on the hepatoprotective effect of D. hamiltonii roots fractions against liver damage. MATERIALS AND METHODS: The current research discussed the fraction from D. hamiltonii root extracts was used. Male Wistar rats (albino strain) were grouped into 4 distinct groups of six animals each. Group I: plain water and vehicle whereas Group II (CCl4 control): CCl4 (1 ml/kg, 20 % v/v in olive oil) over 7 days and vehicle; Over 7 days, Group III received Silymarin 100 mg/kg/day and tap water with 20 % v/v of CCl4, whereas Group IV (treatment group) received DHE 50 mg/kg/day, 100 mg/kg/day, and water. Assessment of biochemical parameters, Mitochondrial modulation, gene expression analysis, and RT-PCR, was used to estimate the protective action of DHEF in CCl4-intoxicated rats. RESULTS: The administration of CCl4 increased levels of total bilirubin (0.63 ± 0.97 mg/dl) plasma amino transferases (110.36 ± 1.13 U/L, 86.56 ± 2.41 U/L and 1.51 ± 1.36 mg/dl respectively) which were mitigated by D. hamiltonii treatment. Activity like Lipid peroxidation and content of nitric oxide also augmented, while the antioxidant action measured by GSH (9.64 ± 0.18 U/mg protein), SOD (3.69 ± 0.22 U/mg protein), and CAT (1.47 ± 0.01 U/mg protein) was reduced. Decalepis hamiltonii root provided substantial restoration of GSH (14.92 ± 0.04 nmol/gm protein), SOD (4.20 ± 0.18 U/mg protein), and CAT (2.71 ± 0.04 U/mg protein) levels. In addition, the acute phase reactants stimulated by CCl4 administration enhanced mRNA expressions of IL-6, IL-10, TNF-a, NF-κß, and COX-2, which were enhanced by D. hamiltonii treatment. CONCLUSIONS: In summary, DHEF protects the liver against CCl4-induced damage, possibly by mitochondrial modulation mechanism. These findings indicate that D. hamiltonii significantly moderates oxidative stress of CCl4-induced hepatotoxicity.

Unveiling the role of gut dysbiosis in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial complicated condition, reflected by the accumulation of extra fat in the liver. A detailed study of literature throws light on the fascinating connection between gut dysbiosis and NAFLD. The term 'gut dysbiosis' describes an imbalance in the harmony and operation of the gut microflora, which can upshoot a number of metabolic disorders. To recognize the underlying mechanisms and determine treatment options, it is essential to comprehend the connection between gut dysbiosis and NAFLD. This in-depth review discusses the normal gut microflora composition and its role in health, alterations in the gut microflora composition that leads to disease state focusing on NAFLD. The potential mechanisms influencing the advent and aggravation of NAFLD suggested disturbance of microbial metabolites, changes in gut barrier integrity, and imbalances in the composition of the gut microflora. Furthermore, it was discovered that gut dysbiosis affected immune responses, liver inflammation, and metabolic pathways, aggravating NAFLD.

Identification of potential drug candidates as TGR5 agonist to combat type II diabetes using in silico docking and molecular dynamics simulation studies.

A cell surface bile acid receptor TGR5 being considered as a novel target for Type II diabetes found to be expressed in various tissues. A major role for TGR5 is to maintain blood sugar levels and increase in energy expenditure. These benefits make it a potential candidate for the treatment of type 2 diabetes, obesity and other metabolic disorder. To date, many novel TGR5 agonists have been synthesized and evaluated in the literature, but very few in silico computational studies have been reported. The discovery of a high-resolution crystal structure of TGR5 in 2020 provides an excellent opportunity for computational screening of potential agonists. In this study, we, therefore, aim to search novel, less toxic TGR5 agonists by iteratively analyzing molecular docking against TGR5 (PDB ID: 7CFN) by means of structure-based virtual screening. The docking score of the designed coumarin derivatives that have been docked successfully varies between -9.4 and -9.0 kcal/mol. The molecular docking and ADMET profile examinations of compounds D1, D5 and D15 revealed that these have a strong affinity for the active site residues of TGR5. In addition, molecular dynamics simulation (MDS) studies have shown the stability of compounds that bind to TGR5. It can be summarized that designed coumarin derivatives seem to have promising activity as TGR5 agonists.Communicated by Ramaswamy H. Sarma.

Herbal-Based Dressings in Wound Management.

Wound management is one of the major global challenges in recent times, and woundassociated infection has a significant impact on the healthcare economy worldwide. Wounds can be acute or chronic type, also diabetic, trauma, accidental, burn wounds and minor cuts, bruises, and rashes, etc. One of the primary treatment options available in these conditions are the use of suitable dressing materials to cover the wound and accelerate the healing process. Since ancient times, according to archaeological theories, medicinal plants and oils have been employed for the treatment of wounds. Today researchers across the globe are focusing their efforts on fabrication of novel dressing materials that can provide the most effective treatment, easy exchange of nutrients, and absorb exudate from the wounds. Very lately, various research groups are also concentrating on the design and development of herb-loaded wound dressings, as herbal preparations contain numerous phytoconstituents with a broad spectrum of pharmacological properties when compared to synthetic drugs and also due to the perceived notion that herbal products are generally safe, even when administered over prolonged periods. They contain numerous bioactive that can act on the various phases of the wound healing process, providing an ideal environment for the healing process. The present review discusses the numerous approaches that are employed for the preparation of dressing materials incorporated with plant-derived phytoconstituents/extracts. This review also provides an insight into the healing process and wound healing agents derived from medicinal plants and oils. The review can serve as a database for researchers working in this field and can help them to select the most appropriate dressing material for the effective delivery of herbal preparations in the management of wounds.

Effect of herbal formulation on glimepiride pharmacokinetics and pharmacodynamics in nicotinamide-streptozotocin-induced diabetic rats.

BACKGROUND: Traditional medicinal herbs are widely consumed in developing countries to treat diabetes as they are perceived to be safer, less expensive, and have fewer side effects as compared to the conventional medicines. Diabecon (DB), Himalaya Herbal Healthcare, India is herbal over-the-counter formulation which contains several herbs that are reported in the traditional texts for the treatment of diabetes. The majority of these herbs have been investigated and found to interfere with the cytochrome pathway. The most common oral antihyperglycemic drug used today in clinical practice is Glimepiride (GP).The CYP2C9 enzyme is mainly responsible for the metabolism of GP. Herein we hypothesize that the co-administration of GP with DB may result in possible Herb-Drug Interactions (HDIs) as DB has the potential to significantly inhibit the CYP2C9 enzyme. OBJECTIVE: In the current study, the pharmacokinetic and pharmacodynamic interactions of GP (0.82 mg/kg) with DB (110.95 mg/kg) was investigated in diabetes induced (Nicotinamide-STZ) rats by co-administering both drugs orally for 21 days. MATERIALS AND METHODS: For the study of the HDI, Bioanalytical RP-HPLC/PDA method for quantifying GP in plasma of rats was developed and validated as per US-FDA guidelines. In vivo pharmacokinetic and pharmacodynamic parameters were studied on day 1 and day 21 post administration. RESULTS: The RP-HPLC/PDA method was successfully employed for quantification of GP in the PK studies. The co-administration of GP and DB in diabetic rats resulted in beneficial pharmacodynamic interactions, but there were no notable changes in the pharmacokinetic parameters of GP. CONCLUSION: This current investigation in an animal model suggests that co-administration of GP and DB may have significant therapeutic benefits in the treatment of diabetes; however, additional research, randomized clinical trials or case studies in humans, is needed.

In-silico Screening of Phytoconstituents on Wound Healing Targets - Approaches and Current Status.

Over recent years, there has been tremendous research focused on the effective utilization of natural products in wound management. Natural or herbal products contain several phytoconstituents that may act on various stages in wound healing and thereby provide a multi-targeted approach especially in the treatment of chronic wounds. Currently, attempts have been made to screen the phytoconstituents present in herbs on various targets involved in wound healing. This review includes a systematic evaluation of scientific reports by various groups of researchers on the herbals evaluated for wound management, their phytochemical profiling, pre-clinical studies, and molecular modeling studies. Various wound targets discussed include Interleukin-1, Interleukin-6, Tumor necrosis factor-α (TNF-α), Thymosin beta-4 (Tß-4) that regulate the early inflammatory stage and the novel T cell immune response cDNA 7(TIRC7) that regulates angiogenesis. Also, neuropeptides P and Y act on the inflammatory, migratory, and proliferation phases, and growth factors like vascular endothelial growth factor family (VEGF) and placental growth factor family (PGF) are involved in angiogenesis, while the role of Fibroblast growth factor in tissue remodeling is discussed. As many of the natural products include polyherbal systems, this approach can help in the judicious selection of a combination of herbs that will act on multiple targets in the wound healing process and provide a multi-factorial approach in wound management.

Herbal Oils for Treatment of Chronic and Diabetic Wounds: A Systematic Review.

BACKGROUND: In the present scenario, diabetes is a growing health challenge, and its occurrence is growing across the globe. Diabetes, with its complications like diabetic wounds, vasculopathy, neuropathy, wound infections, and oxidative stress, is a serious cause of mortality worldwide. INTRODUCTION: Among the various complications, treatment of diabetic foot and ulcers is one of the major concerns in patients who are suffering from diabetes. The causative factors for this condition include increased oxidative stress, high blood glucose levels, vascular insufficiency, and microbial infections, and many a time, if left untreated, it may even lead to amputations of the lower extremities. The present therapy for the treatment of diabetic wounds mainly involves the use of synthetic moieties and other biotechnology-derived biomolecules, including growth factors. Few plant products are also useful in the treatment of wounds. METHODS: Essential oils derived from various herbs are reported to possess significant wound healing potential and promote blood clotting, help to fight infections, and accelerate the wound healing process. Hence, the present review is a systematic analysis of all the available data on the use of the natural oils with their biological source, active phytochemical constituents present, and the probable mechanism of action for the treatment of chronic and diabetic wounds in suitable animal models. A methodical collection of data was performed, and information was searched up to April 2020 in entirety. Key phrases used for the data search include the pathophysiology of wounds, diabetic foot wound and its complications, natural oils for chronic and diabetic wound treatment. RESULTS: This review summarizes the natural oils which are reported in the literature to be beneficial in the treatment of chronic wounds, while some oils have been specifically also studied against wounds in diabetic rats. Essential oils are said to interact with the body pharmacologically, physiologically and psychologically and help in rapid wound healing. However, the majority of the literature studies have demonstrated wound healing activity only in animal models (preclinical data), and further clinical studies are necessary. CONCLUSION: This review provides a platform for further studies on the effective utilization of natural oils in the treatment of chronic and diabetic wounds, especially if oils are to receive credibility in the management of chronic wounds.

COVID-19 vaccination hesitancy in India: State of the nation and priorities for research.

BACKGROUND: Few COVID-19 vaccines were anticipated in India in early 2021. However, little was known about COVID-19 vaccination acceptance among the public. We conducted a nationwide study to understand the public's perception about COVID-19 vaccines in December 2020. METHOD: An online survey was deployed using a multi-item validated questionnaire via social media websites and networking platforms for adults in India. We asked participants about vaccination willingness, concerns about vaccination, and their sociodemographic characteristics. RESULTS: Nationwide, 1638 participants from 27 states/union territories took the survey where the majority of the participant were males (55%), 18-30 years old (52%), urban dwellers (69%), college-educated (81%), without a history of COVID-19 infection (92%). More than a fifth were either unaware of the vaccines (20.63%) or were not sure if they will get the vaccine (27%), and 10% refused to obtain the vaccine. Almost 70% of the population had concerns regarding the vaccines. Statistically significant differences (p<0.01) in awareness about vaccine and acceptability were observed based on age, educational qualifications, and employment status. CONCLUSION: While the majority of Indians would accept the vaccine, given the large population of India, even a small proportion of hesitant individuals would translate to millions of unvaccinated individuals. Strategic measures and policy decisions to enhance the rate of COVID-19 vaccination should be continuously planned and implemented in India.

Analytical Method Development and Validation for Simultaneous Determination of Simvastatin and Mupirocin Using Reverse-Phase High-pressure Liquid Chromatographic Method

Objectives: This study was aimed to develop and validate the use of reverse-phase high pressure liquid chromatographic method for the estimation of simvastatin (SIM) and mupirocin (MUP) simultaneously. Materials and Methods: The chromatographic method developed is optimized for flow rate with the column, solvent, and buffer used and mobile phase ratio, molarity, and pH. The validation of the optimized method and the forced degradation studies of both drugs (under acidic, alkaline, oxidation, heat, light, and neutral conditions) were conducted following the The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. Results: Kromasil C18 column (250 mm × 4.6 mm, 5 µm) with ultraviolet detection at 224 nm and acetonitrile/phosphate buffer (30 mM, 70:30 v/v, pH 3.5; adjustment done using orthophosphoric acid) as mobile phase at a flow rate of 1.1 mL/min were observed to provide a good resolution for MUP and SIM at retention times of 2.32±0.008 and 13.55±0.254 min, respectively, with high accuracy (percent recovery was 99.69±0.82 for MUP and 101.10±0.02 for SIM) and linearity in the range of 5-30 µg/mL (r2: 0.9969 for MUP and r2: 0.9959 for SIM). The diagnostic limit and the lower limit of determination were 0.771±0.234 and 2.338±0.246 µg/mL for MUP and 0.595±0.282 and 1.803±0.334 µg/mL for SIM, respectively. The validated method was used to understand the degradation behavior of both drugs after the forced degradation studies. Conclusion: The analytical method developed is determined to be specific, sensitive, precise, and accurate for the estimation of MUP and SIM simultaneously in the combined dosage form.

Herb-drug interactions in diabetes mellitus: A review based on pre-clinical and clinical data.

Global diabetes epidemic is the major cause of fatality and lethality. As per IDF 2019 report, diabetes caused 4.2 million deaths, approximately 463 million people are living with diabetes and by 2045, this will rise to 700 million. Nowadays, the physicians and common people in both developed and developing countries are using medicinal plants and their formulations to treat diseases with the postulation that organic commodities are safe for consumption. These plants may act as inhibitors or inducers of the Cytochrome P450 or transport and efflux proteins or both and may alter gastrointestinal, renal functions leading to Herb-Drug Interactions. This review intends to focus on the frequently employed medicinal plants, their traditional uses, their Cytochrome P450 inhibition or induction activity, phytochemical, and pharmacological effects, established HDI with the help of in vitro tools, in vivo pharmacokinetics and pharmacodynamics studies to understand the impact of herbs on ADME of the drug and whether it is beneficial, harmful or has no effect respectively. This review will help the physicians and other health care professionals as a reference guide to update their knowledge and expertise about HDI. However, more quality research in this area is needed to evaluate the efficacy of many herbal medicines, thereby reducing side effects and improving the safety of patients.

Novel Niacin Receptor Agonists: A Promising Strategy for the Treatment of Dyslipidemia.

BACKGROUND: Hyperlipidemia is characterized by high level of cholesterol and triglycerides in blood. Various classes of drugs like statins, fibrates, niacin etc. are used for treatment of hyperlipidaemia. OBJECTIVE: Niacin, which is one of the beneficial anti-hyperlipidemic agents, helps decreasing LDL cholesterol by 20 to 40% and causes increase of HDL cholesterol by 20 to 35%. However cutaneous flushing, loss of glucose tolerance, liver toxicity are the reported side effects of niacin therapy responsible for decreased patient compliance. Very recently, the G protein coupled receptor (GPCR); GPR109A located on the adipocytes has been identified as the receptor for activation of niacin. METHOD: In-vitro studies have demonstrated that GPR109A receptor having high affinity for niacin. The present review attempts to provide a systematic presentation of the various chemical classes of compounds that have been reported as novel niacin receptor agonists including pyrazole-3-carboxylic acids, urea derivatives, anthranilic acids, biaryl anthranilides, tetrahydro anthranilic acid, xanthines, barbituric acid, bicyclic pyrazole carboxylic acids, pyrido pyrimidinones, pyrazolyl propionyl cyclohexenamides, pyrazole acids etc. Results: As the design of GPR109A receptor agonists offers a promising solution for treatment of dyslipidemia, this review will be beneficial for medicinal and drug discovery chemists to expediate the process of discovery of new class of anti-hyperlipidemic agent with favorable lipid lowering profile with increase in HDL levels. CONCLUSION: This review explains novel GPR109A receptor agonists for the treatment of dyslipidemia.

Application of Carbon Nanotubes In Drug Delivery of Non-cancerous Diseases: A Review.

Carbon Nanotubes (CNT) are the allotropes of carbon in nanosize dimension and are popular in medicinal field. These nano-based technologies are gaining high interest in the recent years for the treatment of diseases that are previously considered to be impossible to cure. CNTs have gained significance in the treatment of the majority of disorders such as Malaria, Alzheimer's disease, Infectious disease, and Asthma. Moreover, patient's responsiveness also increased in cardiovascular and pulmonary diseases. To date, a number of reviews are available in the literature covering applications of CNT in cancer. However, the purpose of this review is to focus on the use of CNTs in drug delivery of non-cancerous diseases. The novelty of this review is that it is focused on the applicability of CNT in the various non-cancerous diseases. Detailed information was collected from the literature which will guide and encourage researchers to explore the applicability of CNT in various non-cancerous diseases in the future.

Vaccines For Type 1 Diabetes: Prevention or Reversal?

Type 1 diabetes mellitus (T1DM) is an autoimmune disease which leads to the destruction of pancreatic ß-cells, thereby causing insufficient insulin production. Globally, around 98, 200 children and adolescents below 15 years of age and almost 128,900 subjects below 20 years of age develop T1DM annually, along with severe complications deteriorating their quality of life. In India alone, around 15,900 incident cases below 15 years have reported annually. Hence, its prevention and reversal are significant. Unlike other chronic diseases, T1DM involves the presence of various autoantigens, which can be targeted by proper immunisation. The development of reliable immuno-regulatory surrogate markers would be of great benefit. Vaccines can be one of such strategies in the journey to prevent T1DM. It would not only benefit greatly to reduce the sufferings caused due to diabetic complications but could also help to reverse T1DM, by modulating the autoantigenic immunological reactions and prevent further degradation of pancreatic ß-cells. This review collates a wide range of information related to the vaccine studies conducted in animal and human models to prevent and reverse T1DM.

Herb-drug interaction studies of herbs used in treatment of cardiovascular disorders-A narrative review of preclinical and clinical studies.

About 70% of the world population is currently using medicinal herbs as complementary or alternative medicine, which is increasing at a tremendous pace in both developed and developing countries in the last two decades (World Health Organization Medicines Strategy 2002-2005). This increase in consumer demand of medicinal herbs continues despite the rarity of scientific data to establish their safety and efficacy profile. Its popularity is also attributed to several factors, including easy availability, cost effectiveness leading to better purchasing power and general perception that they are safe. Herbs are often administered concomitantly with therapeutic drugs for the treatment of major ailments, raising the potential for herb-drug interactions (HDIs). The major pathways postulated for HDIs involves the cytochrome P450 (CYP450)-mediated inhibition or induction and transport and efflux proteins. In our review, we highlight frequently used herbal medicines for the treatment of cardiovascular disorders (CVD), their established HDIs studied using in vitro tools and in vivo pharmacokinetic and pharmacodynamic assays and case reports. Herbs have been divided into different sections on the basis of availability of HDI data in relevance to cardiovascular drugs: herbs reported to interact with cardiac drugs, herbs yet to be reported for interaction with drugs of any class and herbs reported to interact with drugs of other therapeutic category but not with cardiac drugs. The amount of active phytoconstituents present in the selected herbs and their extent of bioavailability are also mentioned. This review can serve as a quick reference database for physicians and health care professionals involved in CVD treatment, aimed at maximizing clinical outcomes with reduction in adverse and toxic effects.

Data on docking of phytoconstituents of Actinidia deliciosa on dengue viral targets.

Major Phytoconstituents of Actinidia deliciosa were explored for their anti-viral potential against dengue virus (DENV). The docking of these phytoconstituents was performed on 7 viral targets- 4 DENV non structural protein (NS5-SAM binding domain, NS5 RdRp domain, NS3 helicase & NS2B-NS3 protease) and 3 DENV structural proteins (Envelope protein-ß-OD domain, stem domain & Domain III). The analysis was done on the basis of binding affinity, type of interactions (bond type and distance) and interaction with amino acids significant in viral replication. The top 5 phytoconstituents with best docking score have been reported.

Computational data of phytoconstituents from Hibiscus rosa-sinensis on various anti-obesity targets.

Molecular docking analysis of twenty two phytoconstituents from Hibiscus rosa-sinensis, against seven targets of obesity like pancreatic lipase, fat and obesity protein (FTO protein), cannabinoid receptor, hormones as ghrelin, leptin and protein as SCH1 and MCH1 is detailed in this data article. Chemical structures of phytoconstituents were downloaded from PubChem and protein structures were retrieved from RCSB protein databank. Docking was performed using FlexX software Lead IT version 2.3.2; Bio Solved IT. Visualization and analysis was done by Schrodinger maestro software. The docking score and interactions with important amino acids were analyzed and compared with marketed drug, orlistat. The findings suggest exploitation of best ligands experimentally to develop novel anti-obesity agent.

Nitrogen Mustards as Alkylating Agents: A Review on Chemistry, Mechanism of Action and Current USFDA Status of Drugs.

BACKGROUND & OBJECTIVE: Nitrogen mustard derivatives form one of the major classes of anti-cancer agents in USFDA approved drugs list. These are polyfunctional alkylating agents which are distinguished by a unique mechanism of adduct formation with DNA involving cross-linking between guanine N-7 of one strand of DNA with the other. The generated cross-linking is irreversible and leads to cell apoptosis. Hence it is of great interest to explore this class of anticancer alkylating agents. METHODS: An exhaustive list of reviews, research articles, patents, books, patient information leaflets, and orange book is presented and the contents related to nitrogen mustard anti-cancer agents have been reviewed. Attempts are made to present synthesis schemes in a simplified manner. The mechanism of action of the drugs and their side effects are also systematically elaborated. RESULTS: This review provides a platform for understanding all aspects of such drugs right from synthesis to their mechanism of action and side effects, and lists USFDA approved ANDA players among alkylating anticancer agents in the current market. CONCLUSION: Perusing this article, generic scientists will be able to access literature information in this domain easily to gain insight into the nitrogen mustard alkylating agents for further ANDA development. It will help the scientific and research community to continue their pursuit for the design of newer and novel heterocyclic alkylating agents of this class in the coming future.

Synthesis and Biological Evaluation of Novel 2-(4-acetyl-3-methyl- 5-(arylamino) thiophen-2-yl)-3-arylquinazolin-4(3H)-one Derivatives as Potential Anti-inflammatory and Antioxidant Agents.

BACKGROUND: A new series of 2-(4-acetyl-3-methyl-5-(arylamino) thiophen-2- yl)-3-arylquinazolin-4(3H)-one derivatives (11a-11j) were synthesized from acetyl acetone, phenyl isothiocyanate and 2-chloromethyl quinazolinone. OBJECTIVE: Due to side effects of Non Steroidal Anti-Inflammatory Drugs (NSAID), an attempt was made to identify the novel tetrasubstituted thiophene lead compound as potential anti-inflammatory and antioxidant agent. METHODS: Then newly synthesized compounds were characterized by IR spectroscopy, 1H NMR and mass spectrometry. The synthesized compounds were screened for their in vivo anti-inflammatory activity in carrageenan-induced rat hind paw edema model at dose 20mg/kg body weight using diclofenac sodium as a standard drug. The compounds were also evaluated for their in vitro DPPH free radical-scavenging activity and nitric oxide radical scavenging activity at the concentrations of 10, 20, 40, 60, 80 and 100 µg/mL using ascorbic acid as standard drug. RESULTS: The results from carrageenan-induced rat hind paw edema showed that compounds 11e, 11f and 11b show a significant anti-inflammatory activity of 46.61%, 48.94% and 47.04 % protection respectively to inflamed paw but less than diclofenac sodium. Compounds 11h and 11e show good DPPH free radical scavenging and nitric oxide radical scavenging activity, respectively. CONCLUSION: From results, it was observed that highly substituted thiophene scaffold exhibits anti-inflammatory and antioxidant activity.

Discovery of Thiazole Based Bis Heterocyclic System for Anti- Inflammatory Potential.

BACKGROUND: We have developed a new series of 36 substituted thiazole derivatives prepared via reaction of substituted benzothiazole-2-amine with substituted phenacyl bromide. OBJECTIVE: This study was aimed to develop and successfully evaluate anti-inflammatory activity of substituted thiazole derivatives. METHOD: A new series of 36 substituted thiazole derivatives was synthesized and derivatives were characterized by analytical and spectrometric methods like IR, MS, and 1H NMR. The molecular docking was performed for all the synthesized thiazole derivatives to assess their binding affinities to COX-2 isozyme. The best compounds from docking study were subjected for their anti-inflammatory activity by using rat hind paw edema method. RESULTS: Results from carrageenan-induced hind paw edema showed that compounds 3h, 5a, 5e, 9d, and 9h possess significant anti-inflammatory activity. The result from vascular permeability indicating inhibition of vascular permeability with compounds 3h and 9h is significant and results from cotton pellet granuloma formation models show greater degree of inhibition with compounds 3h and 5a to contribute to their significant anti-inflammatory activity. CONCLUSION: This study provides successful development of novel thiazole derivatives. Their binding affinities to COX-2 enzyme were also confirmed, indicating that developed molecules are comparable to diclofenac and hence could be promising anti-inflammatory agents.