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Background: Anaemia is the most common disease that affects mostly females and children and is most prevalent in developing countries. Among various causes sickle cell anaemia is one of them, which is a cause of concern. Sickle Cell Disease (SCD) causes problems like blockage of blood flow, causing pain, and fatigue and also leads to death. Objective: With the advancement in science, diseases that were once considered unable to cure can be stopped or prevented and, in some cases, also be cured. As current therapies for the treatment of sickle cell anaemia are limited, like blood transfusions, bone marrow transfusions, etc., a non-surgical method where plant extracts or compounds were found effective in stopping, preventing, and in some cases reversal of SCD. In this review, we tried to gather information about those plants and compounds. Method: Numerous surveys in the literature were performed to determine the plants which have shown their potential against SCD. Relevant peer-reviewed publications were searched through various databases such as ScienceDirect, PubMed, Google Scholar, Research Gate, etc. Results: A total of more than 50 medicinal plants such as Acacia catechu, Alchornea cordifolia, Anchomanes difformis, Khayase negalensis, Terminalia catappa, etc., have been identified based on their potential against SCD, and 15 compounds such as Butylurea, Glyceraldehyde, Potassium cyanate, urea, etc., have also been identified which could work against SCD. These plants acting on sickle cell anemia on various pathways are also discussed. Conclusion: In this review, an approach was made to study those plants which have an effect against SCD, with proper mechanisms and compounds that show potency against this disease. So that better treatment options could be available for future generations.

Abstract: Nuclear factor-kappa B (NF-κB) is one of the principal inducible proteins and a predominant transcription factor that is known to control gene expression in mammals. It plays a pivotal role in regulating cell signalling in the body under certain physiological and pathological conditions. In cancer cells, such as colon, breast, pancreatic, ovarian, melanoma, and lymphoma, the NF-κB pathway is active. In cellular proliferation, promoting angiogenesis, invasion, metastasis of tumour cells, and blocking apoptosis, the constitutive activity of NF-κB signalling has been reported. Therefore, immense attention has been given to developing drugs targeting NF-κB signalling pathways to treat many types of tumours. They are a desirable therapeutic target for drugs, and many studies have concentrated on recognizing compounds. They may be able to reverse or standstill the growth and spread of tumours that selectively interfere with this pathway. Recently, numerous substances derived from plants have been evaluated as possible inhibitors of the NF-κB pathway. These include various compounds, such as flavonoids, lignans, diterpenes, sesquiterpenes, polyphenols, etc. A study supported by folk medicine demonstrated that plant-derived compounds could suppress NF-κB signalling. Considering this, the present review revealed the anticancer potential of naturally occurring compounds that inhibit the NF-κB signalling and suppress the growth and spread of cancer.

Abstract: About 50.8 million people were diagnosed with diabetes in 2011; the count has increased by 10 million in the last five years. Type-1 diabetes could occur at any age, but predominantly in children and young adults. The risk of developing type II diabetes mellitus in the offspring of parents with DM II is 40% if one parent has DM II and approaches 70% if both parents have DM II. The process of developing diabetes from normal glucose tolerance is continuous, with insulin resistance being the first stage. As prediabetes progresses slowly to DM II, it may take approximately 15–20 years for an individual to become diabetic. This progression can be prevented or delayed by taking some precautions and making some lifestyle amendments, e.g., reducing weight by 5–7% of total body weight if obese, etc. Retinoblastoma protein is one of the pocket proteins that act as crucial gatekeepers during the G1/S transition in the cell cycle. A loss or defect in single-cell cycle activators (especially CDK4 and CDK6) leads to cell failure. In diabetic or stress conditions, p53 becomes a transcription factor, resulting in the transactivation of CKIs, which leads to cell cycle arrest, cell senescence, or cell apoptosis. Vitamin D affects insulin sensitivity by increasing insulin receptors or the sensitivity of insulin receptors to insulin. It also affects peroxisome proliferator-activated receptors (PPAR) and extracellular calcium. These influence both insulin resistance and secretion mechanisms, undertaking the pathogenesis of type II diabetes. Conclusion:: The study confines a marked decrement in the levels of random and fasting blood glucose levels upon regular vitamin D intake, along with a significant elevation of retinoblastoma protein levels in the circulatory system. The most critical risk factor for the occurrence of the condition came out to be family history, showing that patients with first-degree relatives with diabetes are more susceptible. Factors such as physical inactivity or comorbid conditions further aggravate the risk of developing the disease. The increase in pRB levels caused by vitamin D therapy in prediabetic patients directly influences blood glucose levels. pRB is supposed to play a role in maintaining blood sugar levels. The results of this study could be used for further studies to evaluate the role of vitamin D and pRB in regeneration therapy for beta cells in prediabetics.

Abstract: Due to its extensive applications in the field of pharmaceutical chemistry and its potent biological and pharmacological activities, including analgesic, antioxidant, antimicrobial, anticancer, ant-inflammatory, anti-tubercular, antihyperlipidemic, antihistamine, antiviral, anticonvulsant and antiparkinsonian, the heterocyclic molecule occupies a distinct place in the scientific community. The discovery that many synthetic quinazolinone derivatives exhibit a wide range of biological functions has sparked interest in this area of study. The purpose of this review is to collate literature work reported by researchers on quinazolinone and its derivatives for their various pharmacological activities.

Introduction: To obtain the binding site of a model of the human 5-HT1A/2A receptor, a series of substituted 2,4-imidazolidinediones and oxazolidinediones were subjected to flexible docking using GLIDE. Methods: The docking scores that were generated are correlated with the in-vivo affinity data that had already been collected. Results: When combined with a homology model of 5HT1A/2A, the GLIDE docking approach was based on a template for 2-adrenergic receptors. Conclusion: A model for ligand binding in the hydrophobic portion of the binding site was proposed after discussing the impact of the structure and hydrophobic characteristics of the aryl moiety on binding affinities.

A flexible docking of a series of heteroaryl compounds to the binding site of a model of human 5-HT1A/2A receptor was exercised using GLIDE docking methods. The resultant docking scores were used to correlate the in vivo affinity data. The GLIDE docking algorithm when used with a homology model of 5HT1A/2A was based on β2- adrenergic receptor template. The influence of structure and hydrophobic properties of aryl moiety on binding affinities was discussed and a model for ligand binding in the hydrophobic part of the binding site was proposed.

Background Parkinson’s disease (PD) is associated with motor and behavioral dysfunctions. Mitochondrial damage, increased oxidative stress, and the formation of Lewy bodies by misfolded proteins are major pathways for the development of PD. Using antioxidants could delay neurodegeneration in parkinsonism and improve the symptoms. We investigated the neuroprotective effects of quercetin, curcumin, and their combination on the rotenone-induced parkinsonism model. Methods PDwas induced by administration of rotenone 2mg/kg/day for 14 days in rats. Curcumin (100, 150, and 200 mg/kg), quercetin (30, 40, and 50 mg/kg),or their combination were given orally for 14 days concurrently with rotenone and for additional 14 days. On the 28th and 29th days, behavioral and histological studies were carried out. Results In the rotenone-induced parkinsonism model, curcumin and quercetin dose-dependently improved locomotor activity, motor coordination, and mobility. Also, they increased dopamine levels and mitigated the neural damage induced by rotenone. Conclusion Both curcumin and quercetin have neuroprotective effects against parkinsonism. The combination of curcumin and quercetin has more favorable effects than usingeither drug alone.

Curcumin, a natural polyphenol from Curcuma longa, is known to possess diversified pharmacological roles including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic properties; however, its bioavailability is severely limited due to its poor solubility, poor absorption, rapid metabolism, and significant elimination. Hydrazinocurcumin (HZC), a novel analogue of curcumin has been reported to overcome the limitations of curcumin and also possesses multiple pharmacological activities. The present study aimed to evaluate the unexplored pharmacokinetic profile of this agent in experimental rats. Drug formulations were administered to the experimental animals via oral, intravenous and intraperitoneal routes. Blood samples were collected at different pre-determined time intervals to determine the pharmacokinetic parameters. To understand the biodistribution profile of HCZ, tissue samples were isolated from different groups of Sprague–Dawley rats at different time points. The pharmacokinetic parameters of HZC were evaluated after administration through oral (100 mg/kg), intraperitoneal (100 mg/kg) and intravenous (10 mg/kg) routes. Significantly (p

Background: Cancer is one of the major causes of human mortality worldwide. A number of existing antineoplastic medications and treatment regimens are already working in the field, and several new compounds are in different phases of clinical trials. An extensive series of anticancer drugs exist in the market, and studies suggest that these molecules are associated with different types of adverse side effects. The reduction of the cytotoxicity of drugs to normal cells is a major problem in anticancer therapy. : Therefore, researchers around the globe are involved in the development of more efficient and safer anticancer drugs. The output of extensive research is that the quinazoline scaffold and its various derivatives can be explored further as a novel class of cancer chemotherapeutic agents that has already shown promising activities against different tumours. Quinazoline derivatives have already occupied a crucial place in modern medicinal chemistry. Various research has been performed on quinazoline and their derivatives for anticancer activity and pharmacological importance of this scaffold has been well established. Objective: The aim of this review is to compile and highlight the developments concerning the anticancer activity of quinazoline derivatives as well as to suggest some new aspects of the expansion of anticancer activity of novel quinazoline derivatives as anticancer agents in the near future. Methods: Recent literature related to quinazoline derivatives endowed with encouraging anticancer potential is reviewed. With a special focus on quinazoline moiety, this review offers a detailed account of multiple mechanisms of action of various quinazoline derivatives: inhibition of the DNA repair enzyme system, inhibition of EGFR, thymidylate enzyme inhibition and inhibitory effects for tubulin polymerization by which these derivatives have shown promising anticancer potential. Results: Exhaustive literature survey indicated that quinazoline derivatives are associated with properties of inhibiting EGFR and thymidylate enzymes. It was also found to be involved in disturbing tubulin assembly. Furthermore, quinazoline derivatives have been found to inhibit critical targets such as DNA repair enzymes. These derivatives have shown significant activity against cancer. Conclusion: In cancer therapy, Quinazoline derivatives seems to be quite promising and act through various mechanisms that are well established. This review has shown that quinazoline derivatives can further be explored for the betterment of chemotherapy. A lot of potentials are still hidden, which demands to be discovered for upgrading quinazoline derivatives efficacy.

A novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appeared and expanded globally by the end of the year 2019 from Wuhan, China, causing the severe acute respiratory syndrome. During its initial stage, the disease was called the novel coronavirus (2019-nCoV). It was named COVID-19 by the World Health Organization (WHO) on 11th February, 2020. The WHO declared the SARS-CoV-2 virus a pandemic in March 2020. On 30th January, 2020, the first case of Corona Virus Disease 2019 (COVID-19) was reported in India. Currently, the virus has spread to almost every part of the province and the rest of the globe. : On the basis of novel published evidence, we efficiently summarized the reported work with reference to COVID-19 epidemiology, pathogen, clinical symptoms, treatment, and prevention. Several worldwide electronic scientific databases such as Pubmed, Medline, Embase, Science Direct, Scopus, etc., were utilized for extensive investigation of relevant literature. : This review is written in the hope of encouraging people with the key learning points from the underway efforts to perceive and manage SARS-CoV-2, suggesting salient points for expanding future research.

TB is becoming a worldwide problem and it was declared since 1993 by the World Health Organization (WHO), a global health emergency. The current problem of tuberculosis therapy is the emergence of multi-drug resistant (MDR) strains, caused by the improper use of antibiotics in chemotherapy of TB patients. Azatidinones, a β-lactam cyclic amide with four atoms in a ring, has been considered as a magic moiety (wonder nucleus) which possesses almost all types of biological activities. This diversity in the biological response profile has attracted the attention of many researchers to explore this skeleton to its multiple potential against several activities. Present article is sincere attempt to review chemistry, method of synthesis of azatidinones and to study azatidinones synthesized in last few years which have shown potent antitubercular activity.

Alzheimer’s disease (AD) is a multifarious and developing neurodegenerative disorder. The treatment of AD is still a challenge and availability of drug therapy on the basis of symptoms is not up to the mark. In the context of existence, which is getting worse for the human brain, it is necessary to take care of all critical measures. The disease is caused due to multidirectional pathology of the body, which demands the multi-target-directed ligand (MTDL) approach. This gives hope for new drugs for AD, summarized here in with the pyrimidine based natural product inspired molecule as a lead. The review is sufficient in providing a list of chemical ingredients of the plant to cure AD and screen them against various potential targets of AD. The synthesis of a highly functionalized scaffold in one step in a single pot without isolating the intermediate is a challenging task. In few examples, we have highlighted the importance of this kind of reaction, generally known as multi-component reaction. Multi-component is a widely accepted technique by the drug discovery people due to its high atom economy. It reduces multi-step process to a one-step process, therefore the compounds library can be made in minimum time and cost. This review has highlighted the importance of multicomponent reactions by giving the example of active scaffolds of pyrimidine/fused pyrimidines. This would bring importance to the fast as well as smart synthesis of bio-relevant molecules.

A vast advancement has been made in the treatment related to central nervous system disorders especially Parkinson’s disease. The development in therapeutics and a better understanding of the targets results in upsurge of many promising therapies for Parkinson’s disease. Parkinson’s disease is defined by neuronal degeneration and neuroinflammation and it is reported that the presence of the neurofibrillary aggregates such as Lewy bodies is considered as the marker. Along with this, it is also characterized by the presence of motor and non-motor symptoms, as seen in Parkinsonian patients. A lot of treatment options mainly focus on prophylactic measures or the symptomatic treatment of Parkinson’s disease. : Neuroinflammation and neurodegeneration are the point of interest which can be exploited as a new target to emphasis on Parkinson’s disease. : A thorough study of these targets helps in modifications of those molecules which are particularly involved in causing the neuronal degeneration and neuroinflammation in Parkinson’s disease. : A lot of drug regimens are available for the treatment of Parkinson’s disease, although levodopa remains the choice of drug for controlling the symptoms, yet is accompanied with significant snags. It is always suggested to use other drug therapies concomitantly with levodopa. : A number of significant causes and therapeutic targets for Parkinson’s disease have been identified in the last decade, here an attempt was made to highlight the most significant of them. It was also found that the treatment regimen and involvement of therapies are totally dependent on individuals and can be tailored to the needs of each individual patient.

Objective -Plants contain numerous biologically active compounds, many of these have been shown to exhibit therapeutic and antimicrobial properties and therefore they were in use as antimicrobial drugs in traditional medicines. Euphorbia neriifolia Linn. belongs to the family Euphorbiaceae. Assessment of medication implies affirmation of its personality and assurance of its quality and virtue and recognition of nature of debasement. Throughout the years the nature and level of assessment of rough medications has experienced an efficient changes. Hence, in the present study an attempt has been made for effectual qualitative evaluation of dried powdered leaves and stem of Euphorbia neriifolia Linn. by fluorescence analysis. Design & Intervention- The dried powdered sample of Euphorbia neriifolia Linn. leaves and stem has been used to perform fluorescence analysis under the visible day light and UV light of short wavelength (254 nm) and long wavelength (365 nm) for their characteristic colour. Main outcome measures- The ultra violet light creates fluorescence in numerous common items, which don't noticeably fluoresce in sunshine. In the event that the substances themselves are not fluorescent, they may frequently be changed over into fluorescent subordinates or disintegration items by applying diverse reagents. The hues created by these reagents speak to the nearness of dynamic constituents. Results- The fluorescence character of any powdered character of any powdered medication is exceptionally particular and supportive distinctive highlights for the assurance of a medication. Conclusion- The dried powder and herbal extracts of Euphorbia neriifolia Linn. leaves and stem showed varied fluorescence character which is an essential parameter for standardization of herbs. Keywords: Euphorbia neriifolia Linn., Standardization, Fluorescence analysis, Evaluation, Euphorbiaceae.

Background: Vision impairment remains a major health problem worldwide. Elevated intraocular pressure is a prime risk factor for blindness in the elderly. Netarsudil is a Rho-associated protein kinase (ROCK) inhibitor, which also inhibits norepinephrine transport. This narrative review summarizes the properties and clinical significance of netarsudil, a promising drug in topical glaucoma therapy. Methods: We searched PubMed, Medline and Scopus databases using relevant keywords to retrieve information on the physicochemical properties, formulation, mechanism of action, clinical pharmacokinetics, dose and toxicity of netarsudil. Results: Netarsudil showed promising effects in lowering the elevated intraocular pressure by two mechanisms. The US FDA approved netarsudil for clinical use in 2017 under the trademark of Rhopressa® while European Medicines Agency approved Rhokiinsa® in 2019. This drug is available as a 0.02% ophthalmic solution for once-daily topical application. Conclusion: The discovery of netarsudil is a breakthrough in the therapy of glaucoma with proven efficacy in a wide range of eye pressures and is well tolerated in cases with ocular hypertension and chronic glaucoma.

Nipecotic acid is considered to be one of the most potent inhibitors of neuronal and glial-aminobutyric acid (GABA) uptake in vitro. Due to its hydrophilic nature, nipecotic acid does not readily cross the blood-brain barrier (BBB). Large neutral amino acids (LAT1)-knotted nipecotic acid prodrug was designed and synthesized with the aim to enhance the BBB permeation by the use of carrier-mediated transport. The synthesized prodrug was tested in animal models of Pentylenetetrazole (PTZ)-induced convulsions in mice. Further pain studies were carried out followed by neurotoxicity estimation by writhing and rota-rod test respectively. HPLC data suggests that the synthesized prodrug has improved penetration through BBB. Nipecotic acid-L-serine ester prodrug with considerable anti-epileptic activity, and the ability to permeate the BBB has been successfully synthesized. Graphical Abstract.

Diabetes mellitus is one of the aggressive disorders in global society. No pharmacotherapy is available for permanent diabetes cure, although management is possible with drugs and physical activities. One of the recent complications noticed in type 2 diabetes mellitus includes diabetes-induced Alzheimer. It has been proposed that the possible diabetes-induced Alzheimer could be of type 3 diabetes. A variety of cross-sectional studies have proved that type 2 diabetes mellitus is one of the factors responsible for the pathophysiology of Alzheimer. New drug molecules developed by pharmaceutical companies with adequate neuroprotective effect have demonstrated their efficacy in treatment of Alzheimer in various preclinical diabetic studies. Patients of type 2 diabetes mellitus may show the benefit with existing drugs but may not cause complete cure. Extensive studies are being carried out to find new drug molecules that show their potential as antidiabetic drug and could treat type 2 diabetes–induced Alzheimer as well. This review provides an overview about the recent advancement in pharmacotherapy of diabetes-induced Alzheimer. The pathomechanistic links between diabetes and Alzheimer as well as neurochemical changes in diabetes-induced Alzheimer are also briefed.

Background: The connection between inflammation and hyperglycemia leads to diabetes mellitus and its complications. Nutraceuticals are natural sources which can be used as supplement food for the prevention of many disorders. Our aim was studied to the protective role of two antioxidants (Rutin and Chlorogenic acid) with Spirulina fusiformis (SP) on streptozotocin-induced diabetic rats and being challenged with lipopolysaccharide to accelerate the diabetic inflammation. Materials and Methods: Rats were distributed into eleven groups. Each group has 6 rats. Lipopolysaccharide was administered to induced inflammation in diabetes mellitus rats. Orally administered Spirulina fusiformis (500 and 1000 mg/kg), rutin and chlorogenic acid (30 and 60 mg/kg) individually or in combination for 28 days. Metformin (200 mg/kg) was used as a standard drug. Biochemical parameters, body weight, and blood pressure levels were measured at different intervals. Histological studies, Scanning Electronic Microscopy, and gene expression analysis Real-time polymerase chain reaction of NRF2 and inducible nitric oxide synthase gene were analyzed at the end of the experiment. Results: Decreased in blood glucose levels and lipid profile at different intervals were noted with combination drug therapy (Spirulina fusiformis with rutin and Spirulina fusiformis with Chlorogenic acid). Improvement in antioxidant enzymes and pro-inflammatory cytokines levels were decreased on the 45th day. Maximum diastolic blood pressure levels were decreased statistically on the 45th day. Proof of evidence was also supported with these results. Conclusion: Combination therapy was showed excellent results than individual therapy at all parameters.

Vaginal infection is widespread and80% of females encounter such infections during their lives. Topical treatment and prevention of vaginal infection allows direct therapeutic action, reduced drug doses and adverse effects, convenient administration and improved compliance. The advent of nanotechnology results in the use of nanoparticulate vehicle to control drug release, to enhance dosage form mucoadhesive properties and vaginal retention, and to promote mucus and epithelium permeation for both extracellular and intracellular drug delivery.This review discusses the conflicting formulation requirements on polymeric nanoparticles in order to have them mucoadhesive and retentive in vaginal tract, while able to penetrate through mucus to reach adherent mucus layer or epithelium surfaces to prolong extracellular drug release, or facilitate mucosal permeation and intracellular drug delivery.Nanoscale systems are potentially useful in topical vaginal drug delivery. A thorough understanding of their mucus penetration and retention behavior as a function of their formulation, size and surface properties, biorecognition, pH, temperature or other stimuli responsiveness is essential for design of therapeutically effective nanomatrices.

The unique properties of carbon nanotubes (CNTs) make them a highly interesting and demandable nanocarrier in the field of nanoscience. CNTs facilitate efficient delivery of therapeutics like drugs, proteins, genes, nucleic acids, vitamins and lot more. Even though highly beneficial, the biocompatibility of CNTs is a major issue in their questioning their potential application in targeting drug delivery. Studies confirmed subdued toxicity of CNTs following slight modifications like functionalization, controlled dimensions, purification etc. A well-established mechanism for cellular internalization is an insistent need to attain a more efficient and targeted delivery. Recent patents have been thoroughly discussed in the text below.

Substituted piperazine and aniline derivatives of oxazolidin-2,4-diones and imidazolidin-2,4-diones were synthesized by N3 alkylation and screened for their anticonvulsant activity by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test. Among all the synthesized derivatives, compounds 4b, 6c, 6d, 10b, 11a, 11b, and 11d were found to exhibit maximum seizure protection in MES test and were devoid of any neurotoxic effects. Furthermore, the functional activity of these compounds were evaluated in vivo for 5-HT1A receptor affinity by using rectal body temperature and lower lip retraction in rats, while head twitch response in mice was performed for the determination of probable affinity toward 5-HT2A receptor. The results of these tests demonstrated that compounds 4b, 6c, 6d, 10b, 11a, 11b, and 11d exhibited 5-HT1A (pre- and postsynaptic) agonist/antagonist features whereas compounds 11a and 11b exhibited antagonist action for 5-HT2A receptor. From the in vivo studies it was observed that a majority of aniline derivatives (6c, 6d, 11a, 11b, 11d) were found to be more active as compared to their bulky piperazine congeners (4b, 10b). Thus, the overall reduction in the bulkiness of the derivatives without compromising the lipophilicity is well appreciated for providing insights into the structural requirements necessary for development of new effective molecules having anticonvulsant effect.

Extensive attempts to overcome problems related to solubility of drugs for maximizing bioavailability at targeted sites in the body have been made. The issue of drug solubility appears to attract the continued interest of pharmaceutical manufacturers. In this context, nanocrystallization has emerged as an important tool. In the present review, the authors discuss the advantages of nanocrystallized drugs and examine the products available in the market as well as drugs in the pipeline using nanocrystal-based formulations, which are being developed by pharmaceutical companies for drug delivery.

The present research work deals with fabrication of indomethacin loaded gelatin nanoparticles prepared by double desolvation method for controlled drug delivery. Submicron polymeric particles with size 20% in 1 hr) followed by controlled release (> 75% in 12 hr). Among the kinetic models employed, the Higuchi model showed a better fit (R2 > 0.9) with n < 0.43 (Peppas model) indicating a Fickian type of release pattern. The batch 2GA was optimum in terms of size, entrapment efficiency and drug release. Anti-inflammatory activity of the drug loaded nanoparticles (IGNP) and pure drug solution (IDM) was studied by rat paw model and IGNP significantly (P < or = 0.001) decreased the paw volume as compared to IDM. Pharmacokinetic study showed significant enhancement (P < 0.001) of various pharmacokinetic parameters. The observed t(max) value was 3 h for IGNP compared to 1 h for IDM. Cmax of IGNP had higher value (110.81 +/- 8.53 microg/mL) compared to that of IDM (51.66 +/- 7.5 microg/mL). AUC0-12 was 1009.78 +/- 80.24 and 194.33 +/- 46.76/microg x h/mL in IGNP and IDM respectively (relative bioavailability 500%). Further, a good in vitro-in vivo correlation established the formulation for future trials.

In the present study, a series of N(3)-substituted 2,4-imidazolidinediones and oxazolidinediones derivatives (1-16) were synthesized and tested for anticonvulsant activity using the maximal electroshock seizure test. Affinity towards receptor (5-HT1A/2A) was also studied. Their neurotoxicity was determined using the rotarod test. Structures of compounds were confirmed by spectroscopic methods. Compounds 1, 2, 5, 7, 9, and 10 exhibited significant anticonvulsant activity as compared to the standard drug phenytoin. Affinity toward receptor (5-HT1A/2A) was studied in vivo for compounds 1, 2, 5, 7, 9, and 10. Rectal body temperature, lower lip retractions and head twitch responses in Wistar rats/albino mice were determined for this purpose. The tested compounds showed affinity for 5-HT1A and 5-HT2A receptors (agonists/antagonists and presynaptic/postsynaptic). Replacement of piperazine by aniline derivatives provides good outcomes in terms of affinity for 5-HT1A/2A.

Codrug or mutual prodrug is an approach where various effective drugs, which are associated with some drawbacks, can be modified by attaching with other drugs of same or different categories directly or via a linkage. More appropriately one can say combining two different pharmacophores with similar or different pharmacological activities elicit synergistic action or help to target the parent drug to specific site/organ/cells respectively. This approach is commonly used to improve physicochemical, biopharmaceutical and drug delivery properties of therapeutic agents.

Solid- phase synthesis is an approach, where synthetic transformation in carbohydrates are carried out with one of the reactant molecule attached to an insoluble material referred as polymeric support via linker. In recent years, it has been extensively accepted as fast and accurate method for the synthesis of biologically active oligosaccharides. This re- view attempts to focus on various methods of oligosaccharide synthesis by solid- phase including their applications. In the recent years, development of efficient and yet sim- ple procedures for the synthesis of oligosaccharides has been a major goal of carbohydrate chemistry. It is highly desirable to establish methodology for rapid oligosaccharide assembly. Several methods and strategies have been developed so far, which include synthesis in the solution phase leading to ste- reo controlled and high yield reactions. Chemical and enzy- matic synthesis of oligosaccharides on soluble or insoluble polymeric support has also been reported. The advantages associated with the use of an insoluble polymeric support justify further efforts to improve the solid phase strategy. The solid- phase synthesis has been demonstrated to be extremely valuable for routine preparation of oligopeptides and oligonucleotides. The potential usefulness of this proce- dure for the synthesis of other biomolecules is obvious. In past few years, the interest in solid-phase synthesis has in- creased dramatically due to the excitement engendered by the concept of combinatorial chemistry. The Solid-phase synthesis of oligosaccharides, when carried out combinatori- aly, offers the possibility of easy access to a very large num- ber of well-defined oligosaccharides. This can be used as potential tools in glycobiology (1-5).

Epilepsy is the most common chronic neurological disorder of the brain. For several decades different kinds of medications have been used to treat epilepsy. Even though many surgical advances has been made and implemented, medications remain the basis of treatment. The search for noble antiepileptic drugs (AEDs) with more selective activity and lower toxicity continues to be an area of intensive investigation in medicinal chemistry. Additionally, drug resistance is an important clinical problem in epilepsy and is associated with an increased risk of morbidity and mortality. This review intends to present a comprehensive overview on AED in particular along with discussion on some aspects of associated drug resistance and combination therapy.

Ten derivatives of N1 substituted/unsubstituted 5-(4-chlorophenyl)-3-(2-thienyl) pyrazoline were synthesised from chalcone-like intermediate and substituted phenyl hydrazines, hydrazine hydrate, and semi/thiosemicarbazide. The chemical structure of compounds was confirmed by means of IR, 1H NMR, mass spectroscopy, and elemental analysis. The antidepressant and anticonvulsant activities were investigated by Porsolt’s behavioural despair test (forced swimming) and maximum electroshock seizure test, respectively. Rota-Rod test was performed to assess any probable changes in motor coordination induced by the test compounds. Four compounds (IId, IIg, IIi, and IIj) exhibited good activity profile against depression and docking studies confirmed their consensual interaction with monoamine oxidase A. In addition, compounds IIc and IIe showed protection against MES-induced seizures.

The present research work deals with fabrication of indomethacin loaded gelatin nanoparticles prepared by double desolvation method for controlled drug delivery. Submicron polymeric particles with size800 nm were produced possessing narrow polydispersity index (0.5). Entrapment efficiency varied from 27-38% depending upon particle size. No drug polymer interaction was observed by FTIR. DSC study confirmed amorphous nature of nanoparticles. The in-vitro drug release profile showed initial burst release (20% in 1 hr) followed by controlled release (75% in 12 hr). Among the kinetic models employed, the Higuchi model showed a better fit (R20.9) with n0.43 (Peppas model) indicating a Fickian type of release pattern. The batch 2GA was optimum in terms of size, entrapment efficiency and drug release. Anti-inflammatory activity of the drug loaded nanoparticles (IGNP) and pure drug solution (IDM) was studied by rat paw model and IGNP significantly (Por = 0.001) decreased the paw volume as compared to IDM. Pharmacokinetic study showed significant enhancement (P0.001) of various pharmacokinetic parameters. The observed t(max) value was 3 h for IGNP compared to 1 h for IDM. Cmax of IGNP had higher value (110.81 +/- 8.53 microg/mL) compared to that of IDM (51.66 +/- 7.5 microg/mL). AUC0-12 was 1009.78 +/- 80.24 and 194.33 +/- 46.76/microg x h/mL in IGNP and IDM respectively (relative bioavailability 500%). Further, a good in vitro-in vivo correlation established the formulation for future trials.

Soluble Epoxide Hydrolase (sEH) is an important and promising new pharmacologic target for the treatment of acute systemic inflammation. Inhibition of sEH by a highly selective and potent sEH inhibitor (sEHI) elevates the epoxyeicosatrienoic acids (EETs) level in vivo leading to decreased inflammation. To explore the necessary structural requirement of 1, 3-disubstituted ureas as sEH inhibitors for anti-inflammatory activity, the molecular modeling studies have been pursued. A ligand-based pharmacophoric model and atom-based 3D-QSAR have been generated by Phase. Binding interaction as determined by the docking study revealed that these inhibitors interact at active site (ASP 335 & TYR 383) of sEH enzyme. The pharmacophore model was further used as a 3D query for virtual screening to retrieve potential inhibitors.

A novel nano in situ gel forming system of 5-Fluorouracil (5-FU) was investigated for its potential use for conjunctival/corneal squamous cell carcinoma (CCSC). The study was conducted in two steps, in the first step PLA nanoparticles were prepared and characterized; in the second step the drug loaded PLA nanoparticles were dispersed in sodium alginate solution yielding the modified nano in situ system, which were evaluated in rabbit eye. Size and morphology of prepared PLA particles were verified by using dynamic light scattering (DLS), atomic force microscope (AFM) and scanning electron microscope (SEM). In vitro and in vivo study of free 5-FU, PLA nanoparticles and modified nano in situ system were conducted in simulated tear fluid and in rabbit eye respectively. PLA nanoparticles were in size range of 128–194 nm with spherical shape and smooth surface with narrow size distribution. No polymer drug interaction was found as confirmed by FTIR, NMR and DSC. XRD of PLA nanoparticles confirmed that 5-FU was present in the crystalline state. In vitro experiments indicated a diffusion controlled release of 5-FU from both PLA nanoparticles and modified nano in situ system with high burst effect. Modified nano in situ gel system (MNS) significantly increased the Cmax and AUC0-8 in aqueous humor as compared to 5-FU solution and PLA nanoparticles. Higher 5-FU level in aqueous humor was possibly because of increased retention time of gel matrix-embedded drug loaded nanoparticles. Overall results showed the potential of MNS for ophthalmic delivery in the therapy of CCSC.

Malaria is a global health problem that needs attention of drug discovery scientists to investigate novel compounds with high drug efficacy, safety and low cost to counter the malaria parasites that are resistant to existing drug molecules. This is an overview of past to present status of antimalarial drugs including newly researched candidates and also the alternative approaches for the complete control of malaria.

The purpose of the present study is to undertake a docking study of some benzoxazinone derivatives on human peroxisome proliferator activated receptor co-crystallized with an alpha-aryloxyphenylacetic acid agonist using Glide 4.5. The QikProp program was used to obtain the absorption, distribution, metabolism and excretion properties of the analogues. The intermolecular hydrogen bonding interaction of the best-fit ligands were found to be associated with Tyr473, Ser289, Hie 449, Hip 323, Ser 342 and Gly 284 amino acid residue at the receptor active site. Among all the observed interaction with similar binding pattern, the presence of methyl carboxypentyl side chain (Lig. No. 21) showed additional interaction with Ser 342 and the affinity was increased by carboxyl oxygen (as hydrogen bond acceptor) with a best Glide score of -14.54 as compared to the co-crystallized aryloxyphenyl acetic acid which achieved a glide score of -12.50.